CARÁTULA (archivo: Corel Draw 12) · PANAMERICAN JOURNAL OF TRAUMA INSTRUCTIONS FOR AUTHORS Manuscripts and related correspondence should be sent to either Dr. Kimball Maull MD or

CARÁTULA(archivo: Corel Draw 12)

PANAMERICAN JOURNAL OF TRAUMA

INSTRUCTIONS FOR AUTHORS

Manuscripts and related correspondence should be sent to either Dr. Kimball Maull MD or Dr. Ricardo Ferrada MD to the following addresses: Kimball Maull, M.D. FACS, Carraway Medical Center, 1600 Carraway Boulevard, Birmingham, Alabama USA.

1. Manuscript. The original typescript and two high-quality copies of all illustrations, legends, tables and references must be submitted. All copy, including references, must be typed double-spaced on 21 x 27 cm, heavy-duty white bond paper. Margins must be at least 1 inch. A computer diskette or CD containing a file of the article must be included. Files in Word either for IBM-compatible or Apple are preferred. The diskette should be labeled with the author’s names, the title of the article, the type of computer, and the word processing software used.

2. Title. The title must be short, specific and clear. It cannot exceed 45 characters per line, and is limited to two lines. The title page should include the full names, and academic affiliations of all author. Foot notes indicating where the works was done, where orders for reprints should be addressed and those contributing grants for the work should be given at the bottom of the second page. If the manuscript was presented at a meeting, indicate the name of the organization, the place and the date on which it was read.

3. Illustrations. Please send three complete sets of high contrast glossy prints. Figure number, name of senior author, and arrow indicating top should be typed on a gummed label and affixed to the back of each illustration. Cost of color figures, where used, is borne by authors.

4. Summary. A summary of 150 words or less should be submitted in English and Spanish. The summary must include a statement of the problem, methods of study, results and conclusions. A list of key words to be used for indexing should appear at the end of the summary.

5. References. References should be listed in consecutive numerical order as they are cited in the text. Once a reference is cited, all subsequent citations should be to the original number. All references must be cited in the text or tables. References to journal articles should include: authors, title, journal name as abbreviated in Index Medicus, year, volume number, and inclusive page numbers in that order. References to books should include: authors, chapter title, if any; editor in any; title of book; year; city and publisher. Volume and edition numbers, specific pages, and name of translator should be included when appropriate. The author is responsible for the accuracy and completeness of the references and for their correct text citation.

6. Originality & copyright. Manuscripts and illustrations submitted for consideration should not have been published elsewhere except for such preliminary material presented to the Panamerican Trauma Society.

INSTRUCCIONES PARA LOS AUTORES

Los manuscritos y la correspondencia se deben enviar a Ricardo Ferrada MD o Kimball Maull MD a las siguientes direcciones:Ricardo Ferrada, M.D., FACS Departamento de Cirugía, Hospital Universitario del Valle, Calle 5 # 36-08, Cali, Colombia, S.A.

1. Manuscritos. Se debe enviar un original del manuscrito y dos copias de todas las ilustraciones, leyendas, cuadros y referencias. Todas las copias, incluso las referencias, deben ser escritas a doble espacio en papel blanco de 21 x 27 cm. Los márgenes deben ser amplios. Se debe incluir un diskette o CD que contenga el artículo. Son preferibles los archivos en Word IBM compatibles o Apple. El diskette debe ser marcado con el nombre del artículo y de los autores, el tipo de sistema operativo y el procesador de palabras utilizado.

2. Título. El título debe ser corto, claro y específico. No puede exceder de 45 caracteres por línea y está limitado a dos líneas. La página del título incluye el nombre completo y la posición académica de los autores. En la parte inferior de la segunda página se debe indicar dónde se llevó a cabo el trabajo, la dirección para los reimpresos y las donaciones recibidas para su realización. Si el manuscrito se presentó en una reunión científica, indicar el nombre de la organización, el lugar y la fecha de presentación.

3. Ilustraciones. Por favor enviar tres copias completas de las ilustraciones en alto contraste en papel brillante. En la parte posterior de cada ilustración anote el número de la figura, el autor principal y una flecha con la punta hacia el borde superior. Si existen figuras a color, el costo será cubierto por los autores.

4. Resumen. No debe tener más de 150 palabras y debe ser enviado en español y en inglés. El resumen incluye una definición del problema, los métodos de estudio, los resultados y las conclusiones. Al final del resumen se debe adjuntar una lista de palabras claves para efectos de índice.

5. Referencias. Las referencias se citan en orden numérico consecutivo, tal como aparecen en el texto, e incluyen el siguiente ordenamiento: autores, título en el idioma original, nombre de la revista en su forma abreviada según el Index Medicus, año de publicación, volumen de la revista y páginas iniciales y finales. Se recomienda citar hasta cuatro autores en forma completa. Si hay más de cuatro autores, después del tercero, seguido por una coma, se colocan las palabras latinas et al. Las citas de libros incluyen: autores o editor y así se debe identificar (ed.), título del libro, edición, ciudad de publicación, la empresa editorial y año. Las referencias deben ser verificadas por los autores y ésta es una de sus responsabilidades.

6. Originalidad y derechos de autor. Los manuscritos deben ser inéditos y no haber sido publicados en otra parte, excepto como material presentado a la Sociedad Panamericana de Trauma.

Másoportunidades

para la vida

AMAREY NOVA MEDICAL S.A.

Solicítelo en la Librería Médica DistribunaBogotá - Colombia: Autopista Norte Nº 123-93Tels.: (57-1) 215-8335 620-2294 213-2379

Fax: (57-1) 213-2379Buzón telefónico (57-1) 216-1588

E-mail: [email protected] [email protected]

Cualquier inquietud o duda con gusto la atenderemos de inmediato.

www.libreriamedica.com

AUTORES:Ricardo Ferrada, MDAurelio Rodríguez, MDAndrew Pietzman, MDJuan Carlos Puyana, MDRao Ivatury, MD

EDICIÓN:2007 - Segunda edición

PASTA:Dura

FORMATO:21,5 x 27,9 cm

Sociedad Panamericanade Trauma

SEGUNDA EDICIÓN

En preparación

PRÓXIMA APARICIÓN TRAUMA


Editors: RICARDO FERRADA, M.D., Cali, ColombiaRAO IVATURY M.D., Richmond, VirginiaDARIO BIROLINI, M.D., Sao Paulo, Brazil

Assistant Editors: SAMIR RASSLAN M.D., Sao Paulo, BrazilANDREW PEITZMAN M.D., Pittsburgh, PennsylvaniaJORGE NEIRA, M.D., Buenos Aires, Argentina

RAFAEL ANDRADE, M.D.Panama, PanamaJUAN ASENSIO, M.D. Los Angeles, CaliforniaCARLOS BARBA, M.D.Hartford, ConnecticutLUIS BAEZ, M.D.Caracas, Venezuela MARY BEACHLEY, R.N.Baltimore, Maryland RICARDO ESPINOZA M.D.Santiago, ChileEUGENE FAIST, M.D. Münich, GermanyDAVID FELICIANO, M.D. Atlanta, GeorgiaALBERTO GARCIA, M.D. Cali, ColombiaLUIS GRANJA MENA, M.D.Quito, Ecuador GERARDO GOMEZ, M.D. Indianapolis, Indiana FRANCISCO HOLGUIN, M.D.Cartagena, Colombia LENWORTH M. JACOBS, M.D. Hartford, ConnecticutTEOFILO LAMA PICO, M.D.Guayaquil, Ecuador CHARLES LUCAS, M.D.Detroit, Michigan ROBERT MACKERSIE, M.D.San Francisco, CaliforniaKATZIUKO MAEKAWA, M.D.Kitasato, Japan KIMBALL MAULL, M.D.Birmingham, Alabama

ERNEST E. MOORE, M.D. Denver, ColoradoDAVID MULDER , M.D.Montreal, CanadaDAVID ORTEGA, M.D.Lima, Peru RENATO POGGETTI, M.D.Sao Paulo, BrazilABRAHAM I RIVKIND, M.D. Jerusalem, Israel AURELIO RODRIGUEZ, M.D. Pittsburgh, PennsylvaniaCLAYTON SHATNEY, M.D.San Jose, California RAUL COIMBRA M.D.San Diego, CaliforniaJOSE MARIO VEGA, M.D.San Salvador, El Salvador

SECTION EDITORS Critical Care:DAVID HOYT, M.D. San Diego, California

Emergengy & DisasterSUSAN BRIGGS, M.D.Boston, Massachusetts

Infection: RONALD MAIER, M.D.Seattle, Washington

Nursing:ROBBIE HARTSOCK, R.N.Baltimore, Maryland

VIVIAN LANE, R.N.Hartford, Connecticut

Orthopedic Trauma:BRUCE BROWNER, M.D.Hartford, Connecticut

Pediatrics:MARTIN EICHELBERGER, M.D.Washington, D.C.

Plastic Surgery:DAVID REATH, M.D.Knoxville, Tennessee

Prehospital Care:ALEJANDRO GRIFE, M.D.Mexico, Mexico

Coordinación Editorial:DISTRIBUNAEditorial y Librería Médica Autopista Norte 123 - 93Fax: (57) 2132379Tel: (57) 213-2379 (57) 620-2294 Bogotá - Colombia w w w . l i b r e r i a m e d i c a . c o mImpreso por: Gente Nueva editorial

CONTENT CONTENIDO


7. BLOOD SUBSTITUTES IN TRAUMA CAREErnest E. Moore, MD; Jeffrey L. Johnson, MD; Aaron M. Cheng, MD, Forrest R. Sheppard, MD

15. PROTOCOL DRIVEN MEASURES TO REDUCE NOSOCOMIAL PNEUMONIAVicente Gracias, MD, FACS; John J. Gallagher, MSN, RN, CCNS, CCRN

20. RECOMBINANT FACTOR VIIA IN THE COAGULOPATHIC PATIENT - FACT OR FANCY?Juan Carlos Puyana, MD, FACS

24. THE INITIAL MANAGEMENT OF OPEN FRACTURESGary L. Schmidt, MD; Gregory T. Altman, MD; Daniel T. Altman, MD

29. ROLE OF THE GUT IN SIRSErnest E. Moore, MD; Jeffrey L. Johnson, MD; David J. Ciesla, MD; Aaron M. Cheng, MD; Eric L. Sarin, MD

36. HYPERTONIC SALINE - CONFLICTING DATA David B. Hoyt, MD, FACS

39. LIVER WRAPPING PACKING & HEMOSTATICSKimball I. Maull, MD, FACS

41. SYSTEMIC INFLAMATORY RESPONSE SYNDROME AND POSTERIOS ISCHEMIC OPTIC NEUROPATHY AFTER BLUNT TRAUMAAlfredo A Santillan, MD, MPH; Francisco J Agullo, MD; Carlos Vazquez, MD; Alan H Tyroch, MD, FACS

46. MANAGEMENT OF RENAL TRAUMAEddy H. Carrillo, MD

48. THE MODERN APPROACH TO PENETRATING NECK TRAUMAStephen C. Gale, MD; Vicente H. Gracias, MD, FACS

51. OPTIMIZING TRAUMA CARE IN ESPECIAL POPULATIONS: PREGNANT PATIENTGrace S. Rozycki, MD; RDMS, FACS

57. SIMULATION IN TRAINING AND TESTING OF PREHOSPITAL EMERGENCY RESPONDERSJoseph A. Scott MD; S. Barry Issenberg MD

7

BLOOD SUBSTITUTES IN TRAUMA CARE

Ernest E. Moore, MD; Jeffrey L. Johnson, MD; Aaron M. Cheng, MD; Forrest R. Sheppard, MD

Department of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, Denver, CO

Panamerican Journal of Trauma Vol. 13 No. 1 2006 Pages 7-14

The development of blood substitutes spans the past 75 years, but progress in the last decade has been meteoric. The current generation of blood substitutes employed in clinical trials are fundamentally red blood cell (RBC) substitutes; i.e., they are designed primarily to transport oxygen. The products that are now being tested in advanced phase clinical trials are derived from hemoglobin and thus often referred to as hemoglobin based oxygen carriers (HBOCs). The potential clinical benefits of HBOCs are well known (Table 1). The objectives of this brief overview are to out-line potential clinical applications and review the results of HBOCs in recent patient trials.

HEMOGLOBIN TRANSPORT OF OXYGEN AND NITRIC OXIDE

Hemoglobin is recognized as essential for the transport of oxygen (O2) (1). Adult human Hb consists of two α and two β polypeptide chains, each bound to a heme group capable of binding one molecule of O2 (1 g of Hb binds 1.39 mL of O2). The molecular weight of the Hb tetramer is 64,500. The globin subunits of deoxyhemoglobin are held by elec-trostatic forces in a tense conformation with a relatively low affinity for O2.When O2 binds to a heme group, mechano-chemical stresses weaken the electrostatic forces, resulting

in a relaxed conformation; this exposes remaining binding sites and increases O2 affinity 500-fold. The Hill coefficient reflects the cooperative effect of multiple O2 binding sites on Hb, responsible for the sigmoid shape of the oxyhemoglobin dissociation curve. The Hill coefficient of the adult RBC is 2.7 (range 2.4 to 2.9). Factors that modify O2-binding affinity include RBC 2,3-diphosphoglycerate (2,3-DPG) content, the concentration of carbon dioxide and hydrogen ion in blood, and body temperature. Binding of 2,3-DPG between the β chains of Hb stabilizes the tense conforma-tion and thereby reduces affinity for O2. Conversely, loss of 2,3-DPG increases O2 affinity; i.e., it shifts the oxyhemo-globin dissociation curve to the left as defined by a reduced P50. P50 is the O2 tension when the Hb binding sites are 50% saturated; the normal P50 in adults at sea level is 26.3 mmHg. The addition of hydrogen ion or carbon dioxide to blood also reduces the O2-binding affinity of Hb, known as the Bohr effect; oxygenation of Hb reduces its affinity for carbon dioxide—the Haldane effect. Only 10% of carbon dioxide is exported from tissue as carbaminohemoglobin; 80% is transported as bicarbonate, and 10% in physical solution. Finally, decreased core temperature increases the affinity of Hb for O2; i.e., it reduces the P50.

The interaction of Hb with nitric oxide (NO) is conspicu-ously relevant to the efficacy and safety of HBOC use in trauma care (2). Hb can to bind NO through high-affinity ferrous (Fe++) sites on heme nitrosylation (Hb Fe++ NO). Alternatively when NO binds to the heme iron, it can engage in redox reactions with the metal ion, leading to the produc-tion of methemoglobin (Fe++), and the formation of nitrate (NO3). Recently, a second binding site of NO to Hb has been described at the β 93 cysteine residue on the globin chain. Stamler and colleagues (3-5) propose this S-nitrosylation reaction is a key physiologic process designed to transport this vasoactive agent cooperatively with O2. At high O2 satu-ration, Hb assumes the relaxed conformation in which thiol affinity for NO increases, so both O2 and NO are loaded onto Hb. At low O2 levels, NO is unloaded along with O2 from the allosterically modified tense Hb form, which exposes the β

Availability Abundant supplyUniversally compatibleProlonged shelf-life Storage at room temperature

Safety No disease transmissionsNo antigenic reactionsNo immunologic effects

Efficacy Enhanced oxygen deliveryImproved rheologic properties

Table 1. Potential Clinical Benefits of Hemoglobin-Based Oxygen Carriers

Panamerican Journal of Trauma

8 Vol. 13 Number 1 July 2006

93 cysteine site. Gladwin and associates (6) argue that heme nitrosylation (Hb Fe++ NO) is the predominant NO transport mechanism for Hb in the human circulation, and addition-ally this complex facilitates O2 delivery by an enhanced Bohr effect. Whether carried on heme Fe++ or β chains, it is now clear that human Hb can traffic NO, not just consume it.

POTENTIAL ROLE OF HEMOGLOBIN-BASED OXYGEN CARRIERS IN TRAUMA CARE (TABLE 2)

Application LocationI. Perioperative applications

A. Reduce allogeneic RBC transfusions

ED, angiography, OR, ICU

B. Attenuate transfusion immunodulation

OR, SICU

II. Acute hemorrhagic shockA. When stored RBCs unavailable

Field, ED, OR, ICU, remote hospital, civilian disaster, military conflict

B. More efficient resuscitation Field, ED, OR, ICUC. Low volume resuscitation Remote hospital, civilian

disaster, military conflictIII. Regional perfusion

A. Enhance O2 delivery 1)Ischemic reperfused tissue/organ

OR, ICU

2)Inflamed tissue OR, ICU 3)Tumor radiosensitivity HospitalB. Ex vivo organ perfusion Hospital, OR

Table 2. Potential Role of Hemoglobin-Based Oxygen Carriers in Trauma Care

ries. Direct measures of clinical benefit included improved patient survival and reduced complications; an example of a surrogate endpoint was a laboratory measurement expected to correlate meaningfully with clinical benefit. Documenting a direct clinical endpoint for HBOCs was viewed as challenging because this endpoint had never been established for RBCs. Specific recommendations for clinical studies were in three areas: perioperative applications, acute hemorrhagic shock, and regional perfusion. Field trials for severe trauma, where RBCs are not available, were warned as difficult because of safety and ethical issues. Decreased perioperative allogeneic RBC transfusion was regarded as a clinical benefit, but the potential risks of HBOCs would have to be defined and evalu-ated as well. Examples for regional perfusion studies included enhanced tumor radiosensitivity and an adjunct during coro-nary angioplasty (the FDA had approved Fluosol DA in 1989 as an O2 -carrying drug for this setting).

CLINICAL EVALUATION OF MODIFIED TETRAMERIC HEMOGLOBIN IN TRAUMA CARE

Of the modified Hb tetrameric solutions that looked promising in the late 1980s, only one formulation was authorized by the FDA for a phase III study in trauma. HemAssist (Baxter Healthcare, Boulder, CO) consisted of Hb tetramers crossed linked between alpha subunits with bis 3,5 diabromosalicyl fumarate to prevent dissociation into dimers and reduce oxygen affinity. Unfortunately this product failed (13). Regarded by some as a major setback for the clinical implementation of HBOCs, it is important to emphasize that this US multicenter trial of diaspirin cross-linked Hb (DCLHb) for the treatment of severe traumatic hemorrhagic shock was based on the explicit proposal that “DCLHb was tested not as a substitute for blood but rather as an adjunct to the currently used therapies for enhancing oxygen delivery: fluids, blood, and operative intervention.” Although an unexpected outcome raises the issue of com-parable study groups, the difference in the primary study endpoint was concerning: the 28-day mortality for the DCLHb group was 46% (24 of 52), compared with 17% for the the control (normal saline) group (8 of 46).

The authors rationalized this study design because in pre-clinical trials “DCLHb has been shown to be effective in enhancing perfusion in small volumes, suggesting a phar-macologic effect that is independent of hemoglobin.” But the pharmacologic effect was not always reported as ben-eficial. In 1993, Hess and coauthors (14), at the Letterman

Army Institute of Research, reported that in a swine model of hemorrhagic shock DCLHb infusion doubled systemic and pulmonary vascular resistance, and these responses

FDA approval of a new product proceeds through phase I, II, and III studies designed to establish safety and efficacy. FDA regulation defines efficacy as follows: “Effectiveness means a reasonable expectation that. . . pharmacologic or other effects of the biologic product. . . will serve a chemically signifi-cant function in the diagnosis, cure, mitigation, treatment or prevention of disease in man” (7). The Center for Biologics Evaluation and Research (CBER) is the review body for the FDA in the arena of biologies and has published a compre-hensive listing of “points to consider in the safety evaluation of HBOCs” (8). These points encompass characterization of the product, animal safety testing, and human studies; and address the theoretic concerns of Hb solutions raised previ-ously (9-11), including pulmonary and systemic hyperten-sion, organ dysfunction, oxidative tissue injury, synergy with bacterial pathogens, and immunomodulation. In 1994 CBER convened a workshop with the National Heart, Lung and Blood Institute and the Department of the Army to develop “points to consider in the efficacy evaluation of HBOCs” (12). Clinical trial endpoints were divided into two catego-

Blood substitutes in trauma care

9

were associated with a fall in cardiac output. In fact, these changes were equivalent to resuscitation with unmodified tetrameric Hb. The authors concluded, “The decrease in car-diac output associated with the vasoconstriction in the Hb-treated animals was equal to the increase in oxygen-carrying capacity—crystalloid or colloid solutions provided equally rapid correction of the elevated whole blood lactate.” In a followup study (14), the infusion of low-dose (4 mL/kg =14 g Hb) DCLHb into swine subjected to hemorrhagic shock prompted the authors to further warn “pulmonary hyperten-sion and low peripheral perfusion may offset benefits for trauma patients.” Although the authors of the DCLHb trial cited several animal models that appeared to support their study hypothesis, none of these models replicated their study design—a lesson for future conduct of clinical trials with HBOCs. The mechanisms responsible for the vasoconstric-tion resulting from DCLHb administration were proposed before the trauma clinical trial. The increased vascular resis-tance was shown to be predominantly mediated by the scav-enging of NO with an additional component of enhanced endothelin release (16-18). Production of DCLHb has been terminated, but the relevance of these basic mechanisms to future trauma care with HBOCs is clear.

CLINICAL SAFETY OF POLYMERIZED HEMOGLOBIN IN TRAUMA CARE

At this moment, the most promising HBOCs clinically are polymerized Hb solutions (Table 3). Perhaps a coincidence but, as discussed earlier, polymerization addresses several of the problems inherent in tetrameric Hb; ie, enhanced intravascular retention and reduced colloid osmotic activity. Polymerization also appears to attenuate vasoconstriction associated with the infusion of Hb solutions. A proposed explanation is that tetrameric Hb (65 KDa) extravasates

through the endothelium to bind abluminal NO, leading to unopposed vasoconstriction; but polymerized Hb (>130 KDa) remains in the vasculature to bind only luminal NO. Of interest, Hb of the common earthworm, Lumbricus ter-restric, is a polymer with a molecular weight of 400 KDa that circulates extracellularly19. Mice and rats undergoing exchange transfusion with this naturally occurring poly-meric Hb showed no changes in behavior, and nuclear magnetic resonance spectroscopy of the heart confirmed normal O2-carrying capacity (20).

Polymerized HBOCs have undergone extensive preclinical and clinical testing for safety.

Hemopure (Biopure Corp, Cambridge, MA), a polymer of bovine Hb, has been used successfully to reduce alloge-neic RBC transfusion in elective cardiac (21), aortic (22), and hepatic (23) surgery. One study with abdominal aortic reconstruction raised concern about increased systemic vascular resistance (24), an effect identified in normal volunteers (25). Animal studies designed to replicate pre-hospital hypotensive resuscitation for hemorrhagic shock have also been encouraging (26, 27), although the issue of compromised tissue perfusion because of vasoconstric-tion has surfaced (28). Hemopure has been approved for replacement of acute blood loss in South Africa, but there are no published results to date. Clinical testing of Hemolink (Hemosol, Inc, Mississauga, Ontario, Canada), o-raffinose polymerized Hb, has targeted conservation of allogeneic RBC transfusion through enhanced intraoperative autolo-gous donation during coronary artery bypass grafting (29, 30). The pulmonary and systemic vasoconstriction associ-ated with Hemolink infusion (30) is attenuated by general anesthesia (31). Assessment of Hemolink for hemorrhagic shock (32) and regional reperfusion (33) has been limited.

Characteristic Hemopure Hemolink PolyHeme RBCsHemoglobin (g%) 13 g% 10 g% 10 g% 13 g%Unit equivalent (g) 30 g 25 g 50 g 50 gMolecular weight (> 64 KDa) ≥ 95% ≥ 65% ≥ 99% 100%P50 (mmHg) 38 34 29 26Hill coefficient 1.4 1.0 1.7 2.7Oncotic pressure (mmHg) 25 24 23 25Viscosity 1.3 cp 1.1 cp 2.1 cp (whole blood = 5-10 cp)Methemoglobin (%) <10 <7 <8 <1Half-life 19 h 18 h 24 h 31 dShelf-life @ 4° C ≥3 y ≥1 y ≥1.5 y 42 dShelf Life @ 21° C ≥2 y _ ≥6 wk <6 h

Table 3. Characteristics of Hemoglobin Based Oxygen Carriers Versus Stored Red Blood Cells.

Cp = centipoises; P50 = tension when hemoglobin-binding sites are 50% saturated



The mechanism(s) responsible for vasoconstuction has not been established but has been speculated to be largely due to residual tetrameric Hb binding to NO. But alterna-tive mechanisms have been proposed, including increased endothelin, release-enhanced adrenergic receptor sensi-tivity, and reduced arterial wall shear stress (34).

PolyHeme (Northfield lab, Evanston, IL) has been the only product to be evaluated in trauma patients. Under FDA guidance, we initiated clinical trials in trauma to confirm safety with escalating doses of PolyHeme. In the first clinical trial (35). 39 patients received 1 (n = 14), 2 (n =2), 3 (n = 15), or 6 (n = 8) units of PolyHeme instead of stored RBCs as part of their initial resuscitation after acute blood loss. Infusion rates ranged from 1 unit in 175 minutes to 6 units (300 g) in 20 minutes. Although the RBC Hb fell to 2.9 + 0.2 g%, total Hb was maintained at 7.5 + 0.2 g% with PolyHeme. With respect to safety, the patient’s temperature, mean arterial pressure, heart rate, and creatinine clearance did not change during the 72-hour study period. Liver function tests and amylase varied substantially because of patient injuries. Cognizant of the vasoconstriction associ-ated with the DCLHb clinical trial, we designed a study to specifically evaluate the vascular response to PolyHeme infusion in acutely injured patients (36). Patients requiring urgent transfusion were randomized to either PolyHeme (up to 6 units) or stored RBCs during their initial resuscitation. Systemic arterial pressure, pulmonary arterial pressure, car-diac index, and pulmonary capillary wedge pressure were measured every four hours postinfusion. There were no sig-nificant differences between the groups for these indices or the calculated systemic or pulmonary vascular resistance.

Additional issues reported with the clinical use of polymer-ized Hb solutions include interference of laboratory tests that are based on colorimetric changes from dissolved plasma Hb, inaccuracy of O2 saturation monitoring because of met-hemoglobin, mild elevations of serum amylase (but without evidence of pancreatitis), and skin rashes. None of these have been considered clinically important adverse events to date.

CLINICAL EFFICACY OF POLYMERIZED HEMOGLOBIN IN TRAUMA CARE

Perioperative Applications: Reduce Allogeneic RBC Transfusions in Trauma Care

Prompted by the FDA guidelines to demonstrate efficacy, all HBOC companies have pursued what appear to be the simplest clinically; ie, to reduce the need for allogeneic RBC transfusions. In collaboration with David B Hoyt, MD, and the University of California at San Diego, we

conducted a randomized trial in patients requiring urgent transfusion (37). The 44 trauma patients (Injury Severity Score [ISS]=21 + 1.3) were allocated to receive stored RBCs or up to 6 units of PolyHeme as their initial blood replacement. The RBC Hb was equivalent preinfusion (10.4 + 0.4 g% versus 9.4 + 0.3 g%); at end infusion, the RBC Hb of the PolyHeme patients fell to 5.8 + 0.5 g% versus 10.6 + 0.3 g% in the control. The PolyHeme group received 4.4 + 0.3 units, resulting in a plasma Hb of 3.9 + 0.2 g%. The total number of allogeneic RBC transfusions for the control versus PolyHeme was 10.4 + 0.9 units versus 6.8 + 0.9 units (p < 0.05), respectively, through day 1, and 11.3 + 0.9 units versus 7.8 + 0.9 units (p = 0.06), respectively, through day 3. After the initial phase, infusion of 4.6 units of stored RBCs in the control group was equivalent to the 5.2 units in the PolyHeme group. Both volumes presum-ably represent the infused RBCs or PolyHeme lost during the acute hemorrhage. Subsequent replacement volumes were the same, ultimately sparing the PolyHeme group approximately four units of allogeneic RBC transfusion.

With our long-term interest in the pathogenesis of postin-jury MOF (38-41), we then pursued the hypothesis that PolyHeme, in lieu of stored RBCs during initial resuscita-tion, would attenuate the adverse immunoinflammatory effects of allogeneic RBC transfusion. In preparation for these clinical trials, we conducted in vitro studies to test our hypothesis that PolyHeme— free of inflammatory cytokines and lipids—would eliminate the PMN priming previously documented with stored RBCs. Human PMNs were isolated from healthy volunteers and the plasma fraction was sepa-rated from packed RBCs at 42 days of storage in our blood bank (the last day stored RBCs can be transfused clinically, but often the first RBCs infused into trauma patients) (42). The isolated PMNs were incubated with either RBC plasma or PolyHeme at concentrations calculated to be equivalent to 8 units of transfusion. The plasma fraction from three or more units of stored RBCs primed the human PMNs for enhanced superoxide production and elastase release (Figure 1). In our subsequent clinical trial, injured patients requiring urgent transfusion were administered either PolyHeme (up to 20 units = 1,000 g) or stored RBCs for their initial resus-citation (43). PMN priming was determined by the surface expression of CD11b/CD18 in whole blood and superoxide production in isolated PMNs. The study groups (stored RBC [n = 10] versus PolyHeme [n = 9]) were comparable with respect to injury severity (ISS = 27.9 + 4.5 versus 21.9 + 2.7), physiologic compromise (emergency department pH = 7.22 + 0.04 versus 7.19 + 0.08), and Hb transfusion in the first 24 hours (units = 14.1 + 2.0 versus 14.5 + 1). Circulating PMNs from patients resuscitated with stored RBCs mani-fested evidence of priming through increased CD11b/CD18


11

Figure 1. Isolated human neutrophils (PMNs) were incubated with either the plasma fraction from stored RBCs or PolyHeme at concen-trations equivalent to one through eight units of acute transfusion. (A) PMN superoxide production; (b) PMN elastase release. FMLP, formyl-methionyl-leucyl-phenylalanine; PAF, platelet activating factor. * = p<.05

Figure 2. Circulating neutrophils (PMNs) from injured patients who underwent initial resuscitation with either stored RBCs or PolyHeme. (A) PMN CD11/CD18 receptor expression in whole blood; (B) PMN superoxide production in isolated cells. * = p<.05

sE-selectin levels. We have not enrolled a sufficient number of injured patients to definitively address the ultimate study objective—reduction of postinjury MOF. But the incidence of MOF in the acutely injured patients given PolyHeme during their initial resuscitation for whom we had com-plete data (n = 20) was 15%, contrasted with a predicted incidence of 37% (p < 0.05) based on our MOF predic-tion model (age X 33.25, ISS X 27.25, units X 18.05, base deficit X 8.94, lactate X 4.30) (45). In sum, these clinical trials in trauma patients suggest that PolyHeme, used in the early resuscitation of patients with hemorrhagic shock, will attenuate the immunodysfunction associated with stored RBC transfusion and reduce the risk of postinjury MOF.

ACUTE HEMORRHAGIC SHOCK: WHEN STORED RBCS ARE UNAVAILABLE IN TRAUMA CARE

The most compelling indication for an HBOC is the sce-nario in which stored RBCs are unavailable. This potential

expression and enhanced superoxide production (Figure 2). All patients in the PolyHeme group survived; three (30%) in the stored RBC group died of MOF.

To further investigate the impact of early resuscitation with PolyHeme in lieu of stored RBCs, we extended our clinical trial to evaluate the systemic levels of proinflammatory cytokines (IL6, IL8), counterregulatory cytokines (IL10, IL11), and markers of endothelial activation (sICAM, sE-selectin) (44). The study groups (stored RBC [n = 7] versus PolyHeme [n = 18]) were comparable with respect to injury severity. Patients resuscitated with stored RBCs had higher levels of the proinflammatory cytokines IL6 and IL8, and higher levels of the counterregulatory cytokine IL10 (Figure 3), with a trend toward higher sICAM, and



benefit for military use has largely driven the development of HBOCs, but there are also a number of key applications in civilian trauma care. Most conspicuous is the role in prehospital care, particularly for extended transport times. But there are also remote hospitals throughout the country in which stored blood is simply not available or is rapidly depleted when multiple casualties are encountered. There have been well-designed animal models that strongly sug-

Figure 3. Systemic interleukin IL6, IL8, and IL10 from injured patients who underwent initial resuscitation with either stored RBCs or PolyHeme. (A) IL6; (B) IL8; and (C) L10. * = p<.05

gest prehospital low-volume resuscitation with HBOCs can save lives. Despite the appeal, the scientific design and ethical conduct of clinical trials to establish efficacy of HBOCs when RBCs are unavailable remain a challenge (46, 47). To best approximate this scenario, we compared the 30-day mortality in 171 trauma patients given up to 20 units (1,000 g) of PolyHeme, compared with a historic con-trol of 300 surgical patients who refused stored RBCs on religious grounds (48). The trauma patients received rapid infusion of 1 to 2 units (n = 45), 3 to 4 units (n = 4.5), 5 to 9 units (n = 47), or 10 to 20 units (n = 34) of PolyHeme; 40 patients had a nadir RBC Hb < 3 g% (mean =1.5 + 0.7 g%). Total Hb was adequately maintained (mean = 6.8 + 1.2 g%) via plasma Hb added by PolyHeme. The 30-day mortality was 25.0% (10 of 40 patients), compared with 64.5% (20 of 31 patients) in the control patients (Figure 4).

Figure 4. The 30-day motality (M) is compared in patients who refused stored RBC transfusion versus injured patients who were initially resuscitated with PolyHeme. Mortality was significantly less in the PolyHeme group when RBCHb ≤ 5.3 g%.

A personal experience with PolyHeme has convinced me the time has arrived for the FDA approval of an HBOC for trauma care (45). An 18-year-old man arrived by ground ambulance at our emergency department in extremis after a gunshot wound to the abdomen with a high-velocity elk-hunting rifle (30.06, hollow soft point 220 gr, muzzle energy 2,840 ft/lb). Because of immediate availability, 10 units of PolyHeme were administered during the first 14 minutes of in-hospital resuscitation, representing greater than 91% of total circulating Hb at end infusion (RBC Hb = 0.7 g%). The missile entered the left midabdomen and exited directly posteriorly. At laparotomy, we encountered an avulsed shattered left kidney with secondary aortic and vena caval perforations, a partially transected superior mes-enteric vein, and destructive injuries to his distal duodenum, proximal jejunum, midileum, and descending and sigmoid colon. In addition, he had massive soft tissue loss in the ret-roperitoneum, including the psoas and paraspinous muscles,


13

and suffered a concussive spinal cord lesion with resultant paraplegia. The patient received an additional 40 units of packed RBCs during initial laparotomy but ultimately this gentleman survived to discharge without organ failure. We believe the immediate infusion of this HBOC was pivotal in maintaining sufficient O2 delivery during the critical period of massive blood loss to save this man’s life.

With this background, a large multicenter prehospital trail was initiated in the U. S. in January 2007. Severely injured patients, blunt or penetrating, with a SBP < 90 mm Hg due to acute blood loss are randomized at the scene to receive either the standard crystalloid resuscitation or PolyHeme. The study is conducted, by necessity, with exception to informed consent (49). In the hospital, the control group receives stored RBCs as needed while the study group is administered PolyHeme up to six units and then stored RBCs as needed. The primary study endpoint is 30 day mortality; the secondary endpoints include incidence of ARDS and MOF as well as amount of stored RBC transfusion.

THE NEXT GENERATION OF HBOC FOR TRAUMA CARE

The potential efficacy of HBOCs expands well beyond the temporary replacement for stored RBCs. Hemoglobin solu-tions might ultimately prove superior in delivering O2 to ischemic or injured tissue (50). An undisputable byproduct of the intense competition to license HBOCs for clinical use is the enhanced knowledge of the fundamental physiology of hemoglobin. The current generation of HBOCs can save lives today; the next generation may be biochemically tai-lored for specific clinical indications (51, 52).

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3. Gow AJ, Luchsinger BP, Pawloski JR et al: The oxyhe-moglobin reaction of nitric oxide. Proc Natl Aca Sci 1999; 96:9027-9032.

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5. Stamler JS, Jia L, Eu JP et al: Blood flow regulation by S-nitrosohemoglobin in the physiologic oxygen gradient. Science 1997; 276:2034-20.

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7. Department of Health and Human Services: 21CFR601: 25 (d) (2).

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9. Alayash AI: Oxygen therapeutics – Can we tame hemo-globin? Nat Rev Drug Discov 2004;3:152-159.

10. Creteur J, Sibbald W, and Vincent JL: Hemoglobin solutions-Not just red blood cell substitutes. Crit Care Med 2000; 28:3025-3034.

11. McFaul SJ, Bowman PD and Villa VM: Hemoglobin stimu-lates the release of proinflammatory cytokines from leuko-cytes in whole blood. J Lab Clin Med 2000; 135:263-269.

12. Center for Biologics Evaluation and Research: Points to consider on efficacy evaluation of Hemoglobin and perfluoro-carbon based oxygen carriers. Transfusion 1994; 34:712-713.

13. Sloan EP, Koenigsberg M, Gens D et al: Diaspirin cross – linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock – A randomized controlled efficacy trial. JAMA 1999; 282: 1857-1864.

14. Hess JR, Macdonald VW, and Brinkley WW: Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin. J Appl Physiol 1993; 74: 1769 - 1778.

15. Poli de Figueiredo LF, Mathree M, Solanki D et al: Pulmonary hypertension and systemic vasoconstiction may offset the benefits of acellular hemoglobin blood substitutes. J Trauma 1997;42: 847-856.

16. Gulati A, Sen AP, Sharma Ac et al: Role of ET and NO in resuscitative effect of diaspirin cross-linked hemoglobin after hemorrhage in rat. Am J Physiol 1997; 273: H827 - 836.

17. Katsuyama SS, Cole DJ, Drummond JC et al: Nitric oxide mediates the hypertensive response to a modified hemoglobin solution (DCLHb) in rats. Artif Cells Blood Substit Immobil Biotechnol 1994; 22: 1-7.

18. Schultz SC, Grody B, Cole F et al: A role for endothelin and nitric oxide in the pressor response to diaspirin cross-linked hemoglobin. J Lab Clin Med 1993;122:301-308.

19. Fushitan K, Imai K, and Riggs AF: Oxygen properties of hemoglobin from the earthworm lumbricus terrestric. J Biol Chem 1986; 261: 8414-8423.

20. Hirsch RE, Jelicks LA, Wittenberg BA et al: A first evaluation of the natural high molecular weight polymeric lumbricus terrestric hemoglobin as an oxygen carrier. Art Cells Blood Subs Immob Biotech 1997; 25: 429-444.

21. Levy JH, Goodnough LT, Greilich P et al: Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: Results of a randomized, double-blind trial. J Thorac Cardiovasc Surg. 2002;124:35-42.



22. LaMuraglia GM, O’Hara PJ, Baker WH et al: The reduction of the allogenic transfusion requirement in aortic surgery with hemoglobin-based solution. J Vasc Surg. 2000;31:299-308.

23. Standl T, Burmeister MA, Horn EP et al: Bovine haemoglobin-based oxygen carrier for patients undergoing haemodilution before liver resection. Br J Anaesth. 1998;80 (2):189-194.

24. Kasper SM, Walter M, Grune F, et al: Effects of a hemo-globin-based oxygen carrier (HBOC-201 on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery). Anesth Analg. 1996;83:921-927.

25. Hughes GS, Antal EJ, Locker PK, et al: Physiology and phar-macokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med. 1996;24:756-764.

26. Manning JE, Katz LM, Brownstein MR et al: Bovine hemo-globin-based oxygen carrier (HBOC-201) for resuscitation of uncontrolled, exsanguinating liver injury in swine. Shock. 2000; 13:152-159.

27. McNeil JD, Smith DL, Jenkins DH et al: Hypotensive resus-citation using an polymerized bovine-based oxygen carrying solution leads to reversal of anaerobic metabolism. J Trauma 2001;50: 1063-1075.

28. Lee R, Neya K, Svizzero TA, and Vlahakes GJ: Limitations of the efficacy of hemoglobin-based oxygen-carrying solu-tions. J Appl Physiol. 1995;79: 236-242.

29. Carmichael FJ, Biro GP, Agensky L et al: The safety and efficacy of the red substitute Hemolink in patients undergoing elective coronary artery bypass surgery Blood 1999; 94: 1166.

30. Greenburg AG and Mazer CD: The use of an oxygen thera-peutic as an adjunct to intraoperative autologous donation to reduce transfusion requirements in patients undergoing CABG surgery. J AM Coll Surg. 2004;198:373-383.

31. Ning J, Wong LT, Christoff B et al: Hemodynamic response following a 10% top load infusion of Hemolink in conscious, anesthetized and treated spontaneously hypertensive rats. Transfus Med 200; 10: 13-22.

32. Kerger H, Tsai AG, Saltzman DJ et al: Fluid resuscitation with 02 vs non 02 carriers after 2 h of hemorrhagic shock in conscious hamsters. Am J Physiol 1997; 272:H525-H537.

33. Whitley D, Patterson R, Greenburg AG, et al: Cell-free Hemoglobin preserves renal function during normothermic ischemia. J Surg Res 1998;77:187-191.

34. Rohifs RJ, Bruner E, Chiu A et al: Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide. J Biol Chem 1998; 273:12128-12134.

35. Gould SA, Moore EE, Moore FA, et al. Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery, J Trauma 1997;43:325-332.

36. Johnson JL, Moore EE, Offner PJ et al: Resuscitation of the injured patient with polymerized stroma-free hemoglobin

does not produce systemic or pulmonary hypertension. Am J Surg 1998; 176: 612-617.

37. Gould SA, Moore EE, Hoyt DB, et al. The first randomized trial of human polymerized hemoglobin as a blood substi-tute in acute trauma and emergent surgery. J Am Coll Surg 1998;187:113-122.

38. Aiboshi J, Moore EE, Ciesla, DJ, et al. Blood transfusion and the two-insult model of postinjury multiple organ failure. Shock 2001;15:302-306.

39. Botha AJ, Moore FA, Moore EE, et al. Postinjury neutro-phil priming and activation – An early vulnerable window. Surgery 1995;118:35-365.

40. Moore FA, Moore EE< and Sauaia A. Blood transfusion – An independent risk factor for postinjury multiple organ failure. Arch Surg 1997;132:620-625.

41. Silliman CC, Clay KL, Thurman GW, et al. Partial charac-terization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med 1994;124:684-694.

42. Partrick DA, Moore EE, Barnett CC et al: Human polymer-ized hemoglobin as a blood substitute avoids transfusion-induced PMN priming for superoxide and elastase release. Shock 7; 24, 1997.

43. Johnson JL, Moore EE, Offner PJ, et al. Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. J Trauma 2001;50:449-456

44. Johnson JL, Moore EE, Gonzales RJ, et al. Alteration of the postinjury hyperinflammatory response via resuscitation with a red cell substitute. J Trauma In press.

45. Moore EE. Blood substitutes – The future is now. J AM Coll Surg 2003;196:1-17.

46. Huston P, Peterson R. Withholding proven treatment in clinical research. N Engl J Med 2001;345:912-913.

47. McRae AD, Weijer C. Lessons from everyday lives-a moral justification for acute care research. Crit Care Med 2002;30:1146-1151.

48. Gould SA, Moore EE, Hoyt DB, et al. The life-sustaining capacity of human polymerized hemoglobin when red cells may be available. J Am Coll Surg.

49. Department of Health and Human Services. 21 CFR 50.24 and 45 CFR 46.408.

50. Chang TM. Oxygen carriers. Curr Opin Invest Drugs 2002;3:1187-1190.

51. Kavdio M, Pittman RN, Popel AS. Theoretical analysis of effects of blood substitute affininity and cooperatively on organ transplant. J Appl Physiol 2002;93:2122-2128.

52. Winslow RM. Blood substitutes – A moving target. Nat Med 1995;1:1212-1215.

15

PROTOCOL DRIVEN MEASURES TO REDUCENOSOCOMIAL PNEUMONIAVicente Gracias, MD, FACS; John J. Gallagher, MSN, RN, CCNS, CCRN

Director, Surgical Critical CareTrauma Center at PENNPhiladelphia, Pennsylvania


Nosocomial infections add morbidity, mortality and increase costs to patients in the surgical intensive care unit. Pneumonia is the second most common nosocomial infection, second only to urinary tract infections in the hospitalized patient. Nosocomial pneumonia defined as pneumonia occurring greater than 48 hours after hospital admission occurs in 10% to 15% of all trauma patients. Ventilator associated pneu-monia (VAP), a subset of nosocomial pneumonia, occurs in 8% to 24% of all patients receiving mechanical ventilation but at higher rates of 40% to 45% in trauma patients who are mechanically ventilated. VAP can be further categorized as early onset (< 4 days mechanical ventilation) and late onset (> 4days of mechanical ventilation). Early onset pneumonias are generally secondary to antibiotic susceptible community acquired organisms, staph. and strep. species, H.Flu etc. Late onset VAP organisms are commonly resistant noso-comial pathogens, gram-negative rods and pseudomonas species. There is opportunity for significant reduction in the mortality associated with nosocomial pneumonia in the dis-covery and implementation of evidence-based interventions to prevent and reduce the occurrence of this devastating complication in the critically ill patient. Various preventive strategies have be touted to be highly effective at reducing the incidence and thus sequelae associated with VAP.

The development of systems to reduce the occurrence of healthcare associated morbidity and mortality and opportunities to benchmark protocols have been encour-aged through the efforts of industry based organizations such as the Leapfrog Group and the development of new outcome sensitive JCAHO quality core measures focused on critical care. The development and implementation of evidence based practice guidelines is one way to reduce variability in care practices, and improve quality of care. The development of such guidelines relies however, on the presence of useful scientific data that has been generated

in clinical research trials. Limitations in the availability of strong scientific evidence in the form of class I and class II data may be the biggest barrier to developing evidence-based guidelines. Despite this challenge, many professional organizations have developed useful guidelines based on available research. Extensive review by multiple organi-zations such as the Agency for Healthcare Research and Quality (AHRQ) has led to growing scientific evidence of treatment modalities that actually have proven therapeutic benefit. This manuscript will explore current strategies employed in clinical practice aimed at preventing the occurrence of nosocomial pneumonia, the current evidence available to support the use of these strategies and clinical considerations in the implementation of these strategies.

Efforts to prevent nosocomial pneumonia can be classified broadly as those aimed at controlling the transmission of infection from the environment to the patient and those aimed at preventing gastric and oral colonization as well as aspiration.

LIMITING ENDOTRACHEAL INTUBATION AND MECHANICAL VENTILATION

The development of pneumonia as a result of aspiration is related to several factors including host defenses, the quantity of material aspirated and the virulent nature of the organism. Therapeutic interventions such as endotracheal intubation bypass the defenses of the upper airway placing the patient at risk for nosocomial and ventilator associated pneumonia. Therefore, any effort that limits the need for endotracheal intubation and mechanical ventilation or limits the duration of these interventions is desirable. The use of noninvasive ventilation should be employed when possible to limit the need for intubation. This noninvasive ventilation strategy uses a nasal mask or facemask to deliver ventilation and if effective may prevent or delay the need for endotra-cheal intubation. Additional efforts to limit the duration of mechanical ventilation include the application of ventilator liberation protocols and sedation guidelines. Ventilation lib-eration protocols decrease the duration of mechanical ven-


16 Vol. 13 Number 1 October 2006

tilation through application of a standardized approach to the weaning process. The elimination of practice variability streamlines the process reducing the duration of mechanical ventilation. Limiting the duration of mechanical ventilation may also be facilitated through the use of daily sedation holidays or wake up periods. This practice along with daily drug dose tapering can prevent over sedation and extended duration of mechanical ventilation.

ASPIRATION OF SUBGLOTTIC SECRETIONS

The collection of colonized oral secretions in the subglottic region above the endotracheal balloon place the patient at significant risk for aspiration of these secretions and the development of pneumonia. The removal of these secretions can reduce this risk. Proposed methods to remove secre-tions include continuous aspiration of secretions through the use of specialized endotracheal tubes and intermittent scheduled aspiration of secretions using a suction catheter. Endotrachal tubes designed for aspirating subglottic secre-tions have a lumen on the dorsal aspect of the tube above the tracheal balloon connecting to a suction port through which continuous suction may be applied. Secretions are continually removed through this port from the subglottic region. Effectiveness of the device may be limited by the thickness of the secretions. Clinicians must decide which patients would most benefit from this specialized device at the time of intubation or reintubation would be required. While these specialized tubes do cost more than conven-tional endotracheal tubes, the cost may be justified if the incidence of pneumonia is reduced. The second method of secretion removal relies on the scheduled aspiration of secretions as part of oral care. This may be accomplished using either a standard suction catheter or commercial system designed for this purpose. The catheter is placed into the oropharynx to aspirate the secretions.

The scientific support of subglottic secretion aspiration is based on evidence that the practice delays the onset of VAP and may also prevent its incidence. There is no clear reduction in mortality based on this intervention alone. There have been no adverse effects from this practice. The cost of implementing this practice is dependent on the equipment/devices used and the time required by physi-cians and nurses to insert and operate the selected systems. Because of the low risk and potential benefits, aspiration of subglottic secretion had been suggested by the Center for Disease Control (category II) as an intervention that may be helpful in preventing nosocomial pneumonia.

Other efforts that may be helpful include limiting manipu-lation of the endotracheal tube, not deflating the balloon

without first aspirating secretions above the tracheal bal-loon, and preventing unplanned extubation. All these instances may allow for aspiration of orophayngeal secre-tions into the trachea.

USE OF SEMI-RECUMBENT PATIENT POSITIONING

The reflux and aspiration of colonized gastric secretion is a significant risk factor in the development of VAP. Supine positioning has been shown to increase the risk of VAP and has been demonstrated to be independently associated with the development of VAP. Placing the patient in a semi-recum-bent position with the head of bed at 45 degrees may reduce the incidence of reflux and resultant aspiration. Multiple trials have attempted to show reduction in aspiration events and reduced rates of VAP with semi-recumbent positioning. All have demonstrated reduction in risk occurrence however no difference in overall mortality has yet been demonstrated. This intervention is easy to perform, has low cost and small risk but may be limited by patient conditions that preclude head of bed elevation, such as hemodynamic instability and presence of spine injuries. Head of bed elevation may still be achieved in the latter by using the reverse-trendelenberg feature available on most beds. Key to the successful implementation of this intervention is an understanding of its importance by the critical care team and a process for surveillance to determine compliance with head of bed elevation. Education regarding the importance of this intervention in reducing VAP as well as the proper way to measure head of bed elevation is important. Ongoing evaluation of compliance may be accomplished by random audits of the head of bed position at various times of the day in the unit. The American Association of Critical Care Nurses (AACN) has developed a VAP toolbox available at www.aacn.org. Resources that may be downloaded include an audit tool to track compliance with HOB elevation. Caution must be exercised however in maintaining HOB positions of greater than 45 degrees for extended periods of time due to the risk of pressure ulcer development. Efforts such as patient repositioning and implementation of pres-sure relief surfaces may reduce this risk. In the absence of clinical contraindications, HOB elevation is a low risk pro-cedure that is suggested by the CDC as potentially helpful in reducing the incidence of nosocomial pneumonia.

ROTATIONAL AND OSCILLATING SLEEP SURFACES

The utilization of rotational and oscillating bed in patients at risk for pneumonia is based on the premise that such devices

Protocol driven measures to reduce nosocomial pneumonia

17

may prevent atelectasis, improve expansion of collapsed alveoli and mobilize bronchopulmonary secretions. Collard et al described the summary of current favorable evidence supporting the use of oscillating beds as limited to use in the surgical population. There is clearly a need for additional research to determine application in other populations as well as the effectiveness of different degrees of rotation.

The implementation of rotational/oscillation therapy may be limited by certain patient conditions such as agitation, hypotension, arrythmias, and positional oxygen desatura-tion. When possible, the correction of the underlying causes of these conditions may allow therapy to continue. In the case of patient agitation, the benefit of rotational therapy must be weighed against the risks associated with the level of sedation required to continue therapy. Additional care must be taken to avoid the inadvertent removal of invasive lines and tubes during patient rotation.

Although relatively low risk, the implementation of rotational/oscillating sleep surfaces have the potential to be costly. Cost of implementation depends on several factors including the type of bed chosen and the duration of therapy. Guidelines with clear indications for therapy implementation and discontinuance are essential to prevent inappropriate use and associated costs.

Meta analysis of various controlled trial found benefit of oscillating therapy in reducing VAP in surgical patients. Other prospective randomized trials have not demonstrated a benefit. While some research does exist to support the benefits of rotational/oscillating beds there does not appear to be substantial evidence to support the general use of this therapy to prevent nosocomial pneumonia, careful patient selection is warranted.

STRESS ULCER PROPHYLAXIS

The critically ill patient is at significant risk for the devel-opment of gastrointestinal bleeding. In an effort to reduce this risk, pharmacological agents aimed at reducing gastric acidity are used. With the exception of local mucosal pro-tectants such as sucralfate, other agents such as H2 blockers and proton pump inhibitors raise the gastric pH supporting the growth of pathologic bacteria. This colonization of the stomach combined with the presence of gastric intubation, places the patient at risk for reflux of pathologic bacteria into the orophyarynx resulting in colonization of this area and potential aspiration of this hazardous inoculums.

Several meta-analyses have compared the use of sucralfate and H2 antagonists in relation to the development of VAP. There appears to be a lower incidence of VAP associated

with the use of sucralfate over H2 antagonist. However this advantage must be weighed against the risk of GI bleeding since sucralfate does not provide the same level of protec-tion as H2 antagonists in patients at high risk for gastroin-testinal bleeding.

The CDC guidelines consider this issue unresolved based on the current data available and therefore do not make any recommendations as to the superiority of one therapy over another. Low risk patients likely handles well with sucralfate therapy and high risk patients must be monitored closely if sucralfate is used as default prophylaxis agent.

SELECTIVE DIGESTIVE TRACT DECONTAMINATION

Selective use of antimicrobial agents to sterilize the oral cavity and stomach have been proposed as method to eradi-cate pathologic bacteria in the upper GI tract and prevent subsequent aspiration into the lungs. Colonization of the oral cavity with pathologic bacteria was found to occur in up to 100% of critically ill patients after 15 days in the ICU. Oral colonization is usually preceded by gastric colonization with the same organisms. Two general approaches include topical application of antibiotics to the oral cavity to reduce coloni-zation or administration of a short course of IV antibiotics.

Gut Decontamination

Review of the literature reveals a significant reduction in VAP and in some cases a reduction in associated mortality with selective digestive tract decontamination using com-bination of topical and systemic antibiotics. The benefit in reduced mortality was not appreciated with topical agents alone. While this is promising information, there is the risk of developing antibiotic resistance from prophylactic use of antibiotics. No formal cost benefit analysis has been produced. For these reasons, evidence based guidelines developed thus far do not recommend the use of selective gut decontamination.

Oral Decontamination

Selective measures to reduce the presence of pathologic bacteria from the oral cavity include mechanical removal of bacteria from the teeth and oral mucosa through use of a toothbrush or similar device. This process of mechanical cleansing may be combined with topical bacteriocidal agents to produce selective oral decontamination. While topical antibiotics have the potential to cause resistance, other agents such as 1.5% peroxide solution and chlorhexi-dine gluconate 0.12% have not been found to have this drawback. Oral decontamination has been shown to reduce


18 Vol. 13 Number 1 October 2006

the incidence of VAP without effective the colonization rates of the stomach and intestine. Chlohexidine gluconate was shown in one trial to reduce the occurrence of VAP in the cardiac surgery population when employed in protocol that included preoperative use by the patient as a swish and spit prior to intubation.

Oral care protocols designed to provide regular cleansing of the teeth and oral mucosa with selective oral decontamination have been proposed and are currently under study. Individual institutional protocols generally dictate the frequency of cleansing process as well as when or if topical agents such as 1.5% peroxide or chlorhexidine gluconate are used The additional expense of such kits must be weighed against the potential reductions in VAP appreciated over time and addi-tional nursing time available for other patient care needs.

There is currently no adverse effect appreciated in performing oral care with or without the above noted agents. However, there is not currently enough evidence to recommend the use of topical bacteriocidal agents such ad 1.5% peroxide and chlorhexidine gluconate in all patients. The CDC therefore considers this an unresolved issue requiring further study.

ENTERAL FEEDING ROUTE AND METHODS

The use of enteral feeding in the critically ill posses a potential for aspiration through gastroesophageal reflux of stomach contents. Efforts to reduce this occurrence through HOB positioning have already been described. Efforts to further reduce the chance of reflux include the placement of small bore feeding tubes to reduce the opening of the gastro-esophageal sphincter decreasing the opportunity of reflux and post-pyloric feeding tube placement. Enteral feeding has been demonstrated to reduce overall infection rates in various SICU populations. VAP rates have been shown to be positively effected by early directed enteral feeding. Additional efforts to determine the superiority of continuous versus intermittent bolus feeding have also undertaken, as well as the usefulness of motility agents in facilitating gastric emptying. At present, clinical studies do not show a clear benefit for use of small bore feeding tubes, postpyloric placement or method of feeding such as intermittent versus continuous. One potential hazard of intermittent feeding may be high residual volumes leading to reflux. This how-ever may be dependent on the volume of feeding provided. Further research in these areas is warranted.

PREVENTION OF MICROORGANISM TRANSMISSION

Key to the prevention of nosocomial pneumonia is the prevention of transmission of microorgnisms to the patient

from care providers and medical equipment. Intervention such as handwashing as well as evidence based practices for changing and cleaning of equipment are essential.

Hand Washing and Use of Protective Equipment

Handwashing is the easiest way to prevent the transmission of bacteria. Recommendations by the CDC include the use of soap and water if hands are visibly dirty or an alcohol based handwash between patients. Personal protective equipment must be used when the risk of coming in contact with infected secretions exists.

Cleaning and Changing of Respiratory Equipment

Equipment should be sterilized/decontaminated between patient use. Rinsing of equipment during episodes of same patient use should be done with sterile water rather that distilled or tap water. The routine changing of respira-tory equipment such as nebulizers, humidifiers, oxygen delivery devices, ventilator circuits and heat moisture exchangers is not recommended unless visibly contami-nated. Manipulation of these devices unnecessarily risks inadvertent contamination of the system.

SUCTION EQUIPMENT AND PROCEDURES

There is insufficient data to recommend the use of closed suction systems over open systems in preventing VAP. It is recommended that suction systems be changed when vis-ibly soiled as previously noted. There is no clear benefit to the instillation of saline into the trachea during suctioning however; only sterile solution should be used to clear the suction catheter system.

Due to the possibility of cross contamination between suc-tion equipment used for the oral cavity and trachea it is recommended that separate suction lines be used for oral suction devices and tracheal suction devices. Sole and colleagues noted that 94% of oral suction equipment was colonized within 24 hours. The potential to cross-contami-nate the tracheal suction catheter clearly exists if the same tubing is used between the two devices.

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10. Kerver, AJH, Rommes, J.H., Mevissen-Verhage, EAE et al, (1987) Colonization and infection in surgical intensive care patients. Intensive Care Medicine, 13: 347-351.

11. Fourrier, F, Duvivier, B., Boutigny, H., Roussel-Delvallez, M. et al. (1998) Colonization of dental plaque: A source of nosocomial infections in intensive care unit patients. Critical Care Medicine, 26(2), 301-308.

12. Houston, S., Hougland, P., Anderson, J.J., et al. (2002). Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery. American Journal of Critical Care, 11(6), 567-570.

13. Sole, M.L., Poalillo, F. E., Byers, J.F., Ludy, J.E. (2002). Bacterial growth in secretions and on orally intubated patients: a pilot study. American Journal of Critical Care, 11 (2), 141-149.

20

RECOMBINANT FACTOR VIIA IN THE COAGULOPATHICPATIENT – FACT OR FANCY?Juan Carlos Puyana, MD, FACS

Director Trauma/Surgical Critical CareUniversity of PittsburghPittsburgh, Pennsylvania


Severe and uncontrolled hemorrhage is a major cause of death in trauma victims, accounting for close to 40% of mortality in both military and civilian trauma (1, 2). Severe bleeding, surgery and massive resuscitation all interact syn-ergistically in generating the classical lethal triad character-ized by hypothermia acidosis and coagulopathy.

Failure of coagulation in trauma is multifactorial and has been characterized by the combined presence of

1. Coagulation abnormalities resembling disseminated intravascular coagulation (DIC), caused by systemic activation of coagulation and fibrinolysis (3).

2. Excessive fibrinolysis (most probably caused by release of tissue plasminogen activator [TPA] from damaged tissues) (3-5).

3. Dilutional coagulopathy caused by excessive fluid treatment (6).

4. Massive transfusion syndrome resulting in dilution of coagulation factors and impairment of platelet number and function (7).

The repetitive cycle of added hypothermia, mainly related to bleeding and hypotension (8), causes slowing of enzy-matic activities of the coagulation cascade (9) and dysfunc-tion of platelets (10).

Ideally, the introduction of an effective hemostatic agent that could act ONLY at the site of injury, without induc-tion of systemic activation of coagulation, could improve hemorrhage control and reduce hemorrhage-related mor-tality and morbidity in both military and civilian trauma victims (11). A number of agents are being used to achieve hemostasis. Such agents may be used topically or systemi-cally. Topical haemostatic agents include vaso-constrictive agents such as epinephrine and procoagulant agents such

as thrombin, ‘haemostatic fibrin’, gelatin, and cellulose material for example spongostan. Systemically adminis-tered haemostatic agents include coagulation factors in the form of cryoprecipitate and fresh frozen plasma. A general haemostatic agent may be one that enhances full thrombin generation and thereby the formation of a stable, tight fibrin haemostatic plug resistant to premature fibrinolysis.

Patients with profuse bleeding due to extensive surgery or trauma often develop a complex coagulation pattern that includes reduced plasma levels of fibrinogen, FVIII and FV, and decreased platelet counts. These patients may well have an impaired capacity to generate thrombin. Such patients often have lowered plasma levels of a number of various coagulation proteins such as fibrinogen, FVIII, FV etc. In addition, thrombocytopenia is common as well as increased fibrinolysis as a result of massive tissue damage. Several of these factors are important for an adequate thrombin formation as well as for the formation of a tight fibrin plug. Thus, low levels of fibrinogen result in the formation of a loose fibrin structure and to a decreased activation of FXIII, the fibrin-stabilizing factor (12).

Trauma patients with massive bleeding thus may benefit from intravenous rFVIIa in order to help to generate a thrombin peak, which may be enough to form a firm, stable fibrin haemostatic plug and thereby decrease the bleeding (13). Since thrombin has such a crucial role in providing hemostasis, any agent that enhances thrombin generation in situations with impaired thrombin formation may be characterized as a ‘general haemostatic agent’.

MECHANISM OF ACTION

Hemostasis is initiated by the formation of a complex between tissue factor (TF), exposed as a result of a vessel wall injury, and activated FVII (FVIIa) that is normally present in circulating blood. The TF-FVIIa complexes con-vert FX into FXa on the TF-bearing cell. FXa then activates prothrombin into thrombin. This limited amount of thrombin

Recombinant factor VIIA in the coagulopathic patient – Fact or fancy?

21

activates FVIII, FV, FXI and platelets. Thrombin-activated platelets change shape, resulting in exposure of negatively charged phospholipids, which form the perfect template for full thrombin generation involving FVIII and FIX. Full thrombin generation is necessary for complete activation of FXIII and thrombin activatable fibrinolytic inhibitor TAFI to occur. Furthermore, full thrombin generation is important for the fibrin structure of the haemostatic plug (14). From Martinowitz, J Trauma Sept 2001

The addition of rFVIIa to F VIII- or FIX-deficient plasma has been shown to increase thrombin generation in a cell-based in vitro model. Furthermore, extra rFVIIa was found to normalize fibrin clot permeability in vitro and to tighten the fibrin structure as studied by three-dimensional confocal microscopy. These findings indicate that administration of rFVIIa is capable of compensating for the lack of FVIII and FIX. Accordingly, the administration of exogenous rFVIIa has been found to stop bleeding in hemophilia patients and, provided it is given in doses high enough, to allow major surgery to be performed in severe hemophiliacs with inhibi-tors. As rFVIIa enhances thrombin generation on already activated platelets, it has been suggested that rFVIIa may also help to improve hemostasis in other situations involving impaired thrombin generation, such as platelet disorders (thrombocytopenia and functional platelet defects).

High doses of rFVIIa (90-120µg/kg) massively increased the level of FVIIa above the physiological normal state. The immediate result is increase in the generation thrombin. Furthermore exogenous rFVIIa induces hemostasis inde-pendently of tissue factor and factors VIII and IX by binding directly to activated platelets surface with low affinity to generate thrombin in a dose dependant manner (15).

In summary, the use of rFVIIa enhances the normal TF- rFVIIa assembly at the site of injury that in combination with activated platelets form a pivotal complex in the initia-tion of the coagulation cascade. There is a burst of localized thrombin generation on the activated platelet surface leading to site-specific hemostasis. High doses of rFVIIa causes activation of the extrinsic pathway via activated platelets in an manner independent of TF, FVIII, IX and X (14).

PHARMACOLOGY

Recombinant Factor VIIa is manufactured using DNA bio-technology in cultured cells and purified using monoclonal antibodies. There is no risk of transmission of human pathogens during this process. The hemostatic effect only occurs after rFVIIa has made contact with tissue factor at the sites of injury. In most cases there needs to be disruption

of the vascular endothelium for TF to be exposed to circu-lating rFVIIa. In fact intravenous administration of rFVIIa does not induce a systemic activation of coagulation. TF however has been described in atherosclerotic plaques, tumor cells and monocytes. Especially under cytokine or endotoxin activation.

Administration of rFVIIa shortens the PT and PTT but does not affect levels of thrombin, fibrinogen or platelet count. The half-life of rFVIIa is 2.7 hours and 1.3 hours for children less than 15 years however there is consider-able variation between individuals. Initial work in humans indicates that a dose of 90 to 110 µg/kg of rFVIIa given as a bolus should be repeated every 2 hours over a 24-hour period. Intervals may be increased thereafter according to the response and severity of bleed (16).

SAFETY

Since tissue factor may be expressed under pathological conditions such as atherosclerosis, sepsis, or cancer then a theoretical risk of thrombo embolic complications such as stroke or myocardial infarction may be associated wit the use of rFVIIa in these specific circumstances. Furthermore, conditions in which there is an increased thrombo embolic risk, such as disseminated intravascular coagulation (DIC) may also lead to complications. In theory, there would be a similar risks in any condition with injured or apoptotic cells, such as in crush injury, blast injury, sever blunt trauma and in patients with tissue necrosis.

According to the manufacturer’s information (14) between 1996 and 2000, more than a million mg of rFVIIa had been administered which is equivalent to close to 160,000 stan-dard human doses of 90 µg/kg in more than 7000 patients. So far there have been 7 events of CVA (4 fatal), 8 myocar-dial infarctions (1 fatal) and 1 patient with myocardial isch-emia. Other reported and possible adverse events include DIC, acute renal failure, and DVT.

STUDIES ON RFVIIA IN TRAUMA AND SURGERY

A swine model of severe liver injury has been described to establish whether rFVIIa could be used as an adjunct for liver packing in a damage control setting. In this setting, the animal model attempt to mimic the bloody vicious cycle of hypothermia, acidosis and coagulopathy after inducing a grade V liver injury. Here the administration of rFVIIa reduced the volume of blood loss and restore normal coagu-lation in conjunction with surgical packing (17). A similar study was performed by a different group also in swine, however these animals were not hypothermic and had an



avulsion of the median lobe of the liver performed to induce uncontrolled intra abdominal bleeding. These animals were treated with rFVIIa after a 10% in base line blood pressure occurred. In this second study there was no difference in total blood volume lost, however the rFVIIa group had improve PT and improved blood pressure response (18). In neither study was survival statistically different between groups.

Two other studies have shown promising results in animals using very high doses (720 µg/kg) of rFVIIa (19, 20). More recently, Sapsford et al demonstrated improved survival in a pig model of uncontrolled hemorrhage using 180 µg/kg of rFVIIa. They studied 27 animals and observe them for 6 hours after injury. They created a 4mm slit in the infra renal aorta. The authors concluded that there is a potential indica-tion for prehospital (battlefield) administration of rFVIIa specifically in a model of non compressible hemorrhage (21). An in vitro study reported by Meng et al indicated that rFVIIa may not be efficient in acidosis but hypothermia has little effect on rFVIIa efficacy. These authors recom-mended that clinicians who may contemplate using FVIIa in trauma patients take note of the level of acidosis present and consider biochemical correction of acidosis before administration of FVIIa. Because of the profound effect of pH on the prothrombinase (FXa/FVa) complex, correction of acidosis may by itself improve hemostasis (22).

Martinowitz published a preliminary study on seven severe trauma patients in September 2001. Three patients had severe high velocity penetrating trauma, and four suffered blunt trauma. They had all received multiple transfu-sions and conventional interventions without achieving hemostasis. In all cases the administration rFVIIa caused a cessation of the diffuse bleeding and their coagulation parameters normalized (23).

Both animal and human data indicated that there is a need for more research in the field using greater number of indi-viduals both in human and animal research as well long term follow up observations to understand the issues regarding possible complications related to increased thrombosis.

Although definitive studies remain to be performed, advo-cates for the use of rFVIIa in trauma patients suggest that there may be two conceptually different indications for rFVIIa. A prehospital or battlefield indication in which rFVIIa could be given in the ambulance before arriving to the trauma center. This approach could have an even higher impact in military trauma. In battlefield conditions, the incidence of severe penetrating injuries combined with scenarios with multiple casualties, limited resources and prolonged evacuation times would indicate that rFVIIa

could be administered in a much earlier fashion perhaps before hypothermia and acidosis occurred with the objec-tive of enhancing the therapeutic window for intervention. The second indication would be at the trauma center as an adjuvant of damage control management.

REFERENCES

1. Gofrit ON, Leibovici D, Shapira SC, et al. The trimodal death distribution of trauma victims: military experience from the Lebanon War. Mil Med 1997; 162(1):24-6.

2. Sauaia A, Moore FA, Moore EE, et al. Epidemiology of trauma deaths: a reassessment. J Trauma 1995; 38(2):185-93.

3. Gando S, Tedo I, Kubota M. Posttrauma coagulation and fibrinolysis. Crit Care Med 1992; 20(5):594-600.

4. Kapsch DN, Metzler M, Harrington M, et al. Fibrinolytic response to trauma. Surgery 1984; 95(4):473-8.

5. Risberg B, Medegard A, Heideman M, et al. Early activa-tion of humoral proteolytic systems in patients with multiple trauma. Crit Care Med 1986; 14(11):917-25.

6. Gubler KD, Gentilello LM, Hassantash SA, Maier RV. The impact of hypothermia on dilutional coagulopathy. J Trauma 1994; 36(6):847-51.

7. Reiss RF. Hemostatic defects in massive transfusion: rapid diagnosis and management. Am J Crit Care 2000; 9(3):158-65; quiz 166-7.

8. Bergstein JM, Slakey DP, Wallace JR, Gottlieb M. Traumatic hypothermia is related to hypotension, not resuscitation. Ann Emerg Med 1996; 27(1):39-42.

9. Krause KR, Howells GA, Buhs CL, et al. Hypothermia-induced coagulopathy during hemorrhagic shock. Am Surg 2000; 66(4):348-54.

10. Valeri CR, Feingold H, Cassidy G, et al. Hypothermia-induced reversible platelet dysfunction. Ann Surg 1987; 205(2):175-81.

11. Hedner U. General haemostatic agents--fact or fiction? Pathophysiol Haemost Thromb 2002; 32 Suppl 1:33-6.

12. McDonagh J, Fukue H. Determinants of substrate specificity for factor XIII. Semin Thromb Hemost 1996; 22(5):369-76.

13. Hedner U. NovoSeven as a universal haemostatic agent. Blood Coagul Fibrinolysis 2000; 11 Suppl 1:S107-11.

14. Sapsford W. The potential use of recombinant activated factor VII in trauma and surgery. Scand J Surg 2004; 93(1):17-23.

15. Monroe DM, Hoffman M, Oliver JA, Roberts HR. A possible mechanism of action of activated factor VII independent of tissue factor. Blood Coagul Fibrinolysis 1998; 9 Suppl 1:S15-20.

16. Erhardtsen E. Pharmacokinetics of recombinant activated factor VII (rFVIIa). Semin Thromb Hemost 2000; 26(4):385-91.

Recombinant factor VIIA in the coagulopathic patient – Fact or fancy?

23

17. Martinowitz U, Holcomb JB, Pusateri AE, et al. Intravenous rFVIIa administered for hemorrhage control in hypothermic coagulopathic swine with grade V liver injuries. J Trauma 2001; 50(4):721-9.

18. Lynn M, Jerokhimov I, Jewelewicz D, et al. Early use of recombinant factor VIIa improves mean arterial pressure and may potentially decrease mortality in experimental hemor-rhagic shock: a pilot study. J Trauma 2002; 52(4):703-7.

19. Jeroukhimov I, Jewelewicz D, Zaias J, et al. Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury. J Trauma 2002; 53(6):1053-7.

20. Schreiber MA, Holcomb JB, Hedner U, et al. The effect of recombinant factor VIIa on coagulopathic pigs with grade V liver injuries. J Trauma 2002; 53(2):252-7; discussion 257-9.

21. Sapsford W KE, Watts S, Kenward C, Cooper GJ,. Intravenous Recombinant Activated Factor VII Improves Survival in a Pig Model of Uncontrolled Hemorrhage From an Aortotomy. Advanced Technology Applications in Combat Casulaty Care (ATACC). St Pete Beach, Fl USA, 2003.

22. Meng ZH, Wolberg AS, Monroe DM, 3rd, Hoffman M. The effect of temperature and pH on the activity of factor VIIa: implications for the efficacy of high-dose factor VIIa in hypo-thermic and acidotic patients. J Trauma 2003; 55(5):886-91.

23. Martinowitz U, Kenet G, Segal E, et al. Recombinant acti-vated factor VII for adjunctive hemorrhage control in trauma. J Trauma 2001; 51(3):431-8; discussion 438-9.

24

THE INITIAL MANAGEMENT OF OPEN FRACTURES

Gary L. Schmidt, MD; Gregory T. Altman, MD; Daniel T. Altman, MD

Department of Orthopaedic SurgeryDivision of Orthopaedic TraumaAllegheny General HospitalPittsburgh, Pennsylvania


ASSESSMENT

An open fracture is usually the result of a high energy injury. Therefore evaluation of the patient with an open fracture must always begin according to the Advanced Trauma Life Support (ATLS) protocol. Often this is performed by a general surgeon with specialty training in trauma/critical care. Once the airway and circulation have been stabilized, attention can be turned to other injuries, including those of the musculoskeletal system.

In the emergency room, orthopaedic evaluation of the trauma patient must include a neurovascular examination of all extremities, inspection and palpation of the long bones and spine, manual compression of the pelvis and brief range of motion testing of all major joints. Particular attention must be paid to the condition of the integument, as soft tissue injury is often less obvious than bony fractures but may ultimately determine the extent of disability. Soft tissue injury associ-ated with closed fractures may be classified according to the system of Tscherne (1). For open injuries, the Gustilo clas-sification (2,3) has been shown to provide prognostic signifi-cance (4). Even with this system, there has been shown to be significant interobserver disagreement when classifying injuries (5). In the event an open fracture is found, immediate intravenous antibiotics should be administered. In this situ-ation Zalavras and Patzakis (6) have conjectured that these drugs be considered therapeutic rather than prophylactic.

In the case of vascular compromise, immediate reduction of obvious deformity is warranted in an attempt to return circulation to the ischemic limb. If restoration of limb align-ment fails to provide return of blood flow, further emergent work-up is indicated. While direct exploration may be indi-cated in some circumstances, typically angiography will serve as the best tool in evaluation of the entire circulatory network of the affected extremity. This may be done in a

dedicated angiography suite or perhaps more expediently performed in the operating room.

If all extremities appear adequately perfused following initial evaluation in the emergency room, the orthopaedic manage-ment of open fractures should proceed with the application of sterile dressings and appropriate temporary immobiliza-tion. In our institution this typically means saline-soaked gauze is placed directly over the open wound and a plaster splint is fashioned to provide temporary stabilization. In the event that other surgeons are simultaneously performing diagnostic and/or therapeutic interventions, pre-fabricated splints can be applied rapidly to facilitate patient transport.

Adequate radiographic visualization of all musculoskeletal injuries is required so that pre-operative planning can be done appropriately. Orthogonal radiographs of one joint above and one joint below each area of suspected injury are mandatory to insure that surgical planning is feasible and to rule out other injuries. Often distracting injuries can result in other more subtle injuries being overlooked. In cases such as vascular injury, where adequate pre-operative radio-graphs may not be available, the orthopaedic surgeon must have a high index of suspicion for other occult fractures. High resolution intra-operative fluoroscopy can be used to investigate for other potentially significant fractures.

OPERATIVE MANAGEMENT

Irrigation and Debridement

Open fractures should be treated in the operating room as quickly as is possible. While some (7, 8) have challenged this view, it is widely held that early intervention offers the greatest chance at prevention of infection. As splints are removed, gross external contamination may be removed via surgical scrub brushes, alcohol-soaked gauze or other sim-ilar cleaning agents. Pneumatic tourniquets may be placed on the affected limb but should only be inflated in the case of significant intra-operative bleeding. Any further ischemia to the injured extremity should be avoided. In addition any

The initial management of open fractures

25

further soft tissue damage should be minimized by avoiding excessive tissue manipulation or exposure (such as repeated examination of the wound in the emergency department). The affected extremity is then prepped and draped in the usual fashion with betadine scrub followed by betadine paint. Pure iodine should be avoided as it is caustic to exposed soft tissue at the open fracture site (9, 10). Operative treatment should begin with thorough irrigation of the contaminated wound. The best manner to accomplish this remains an area of debate. High pressure pulsatile lavage has been shown in vivo to be superior to bulb syringe irrigation in removing debris from wounds (11, 12). However, in tenuous wounds we recommend low pressure or bulb syringe irriga-tion in order to minimize trauma to the tissues. Also, there is some evidence to suggest that the use of high pressure pulsatile lavage may exert negative biomechanical effects on fracture healing in animals (13). The routine addition of anti-biotics to irrigation was not recommended by Anglen (14) given the limited clinical efficacy, significant cost, potential for allergic reaction, and the promotion of bacterial resis-tance. The addition of detergent solutions to irrigation fluids has shown improved efficacy in removing bacteria from bone in the laboratory and may become more commonly utilized in the future (15). The volume of irrigation to be used is not well established in the literature (14). Hence our treatment is individualized based on the severity of the injury and the level of contamination present. A recommended volume of 3 liters per fracture grade serves as a rough guideline. During irrigation of an open fracture it is essential to recreate the initial deformity and/or dislocation in order to facilitate a thorough cleansing of the entire injured area.

Debridement of open fractures should be systematic and meticulous. It will almost always be necessary to extend the margins of the traumatic wound in order to adequately assess the extent of deep soft tissue disruption. Beginning superficially, skin edges should be trimmed to healthy tissue. Subcutaneous fat which has been traumatized likewise must be excised. A thorough examination of muscle bellies in the affected compartment is undertaken to ensure their vitality. The so called “4 C’s” of contractility, color, consistency, and capacity to bleed have been previously described to determine which muscle remains viable (16). The nature of the injury itself should determine the extent to which soft tissues must be excised. While reconstruction always remains in the mind of the orthopaedic surgeon, the pre-vention of infection should be the primary goal during the early phases of treatment of any open fracture. Throughout debridement particular consideration must be given to the handling of the soft tissues. Untraumatized, full thickness flaps of healthy, well-vascularized tissue will heal best.

In order to prevent infection, devitalized fragments of bone should be removed from the wound. Those without remaining soft tissue attachments have little chance of healing but do serve as possible future sequestra. One exception to this rule may be in the case of articular fragments. Here the loss of a single bony fragment may render a joint useless and painful.

Following the conclusion of irrigation and debridement of a highly contaminated wound, it is our routine to com-pletely re-prep, re-drape the extremity and use a clean set of instruments for the remainder of surgery. Some authors (17) have recommended against this practice given its lack of proven efficacy. Having completed a wide and thorough debridement of the wound, surgery can now proceed with skeletal stabilization.

Skeletal Stabilization

Osseous stability can be provided in multiple ways and will vary based on the nature and location of the fracture. External fixators, intramedullary nails, and plates are the most commonly used hardware for internal fixation of open fractures. While upper extremity long bone fractures are most frequently fixed with plate osteosynthesis, lower extremity trauma has been treated with intramedullary nailing with good results (18-20).

Today external fixators are most frequently used as tempo-rary measures to provide stability during the initial stages of treatment of an open fracture. External fixators may be applied quickly and far removed from the zone of injury. Hence they provide rapid stabilization and facilitate safe transport in the unstable patient while simultaneously beginning to provide a stable environment in which soft tissues can begin to heal. While external fixators may be used for definitive treatment, they have been found to have a significant rate of complications (including pin tract infections and increased malalignment) (21).

Intramedullary nailing of open lower extremity fractures has become the gold standard for most diaphyseal fractures. While previously there had been controversy regarding the reamed vs. unreamed nail, it has now been shown that reamed nails can safely be used in the treatment of open femur and tibia fractures (18, 19). It is our preference to “sound” the canal in open fractures. By just reaming to the initial point of cortical chatter, it is our intent to place a large enough nail to provide stability (and prevent cross-lock breakage) without vastly disrupting the endosteal vascular supply of the affected long bone.

Plating is primarily used in the treatment of open fractures of the long bones of the upper extremity. While the rich



blood supply of the upper extremity makes the development of osteomyelitis less common than in the lower extremity, the surgeon still must be cognizant of exposed hardware in cases where soft tissue defects will result in the plate remaining uncovered at the conclusion of the case. In these cases, external fixation is used initially, and staged delayed definitive fixation can be simultaneously combined with soft tissue coverage. Plating for open fractures in the lower extremity has been found to have unacceptably high rates of fixation failure and infection and hence is not routinely utilized or recommended (22, 23). Newer locked plating technology is being studied to assess its biomechanical advantages in comparison to traditional plating (24). This may provide the surgeon with a new option for the treatment of difficult peri-articular fractures. However, clinical studies in the setting of open fractures remain yet unpublished.

Wound Closure

The manner of wound closure is dictated by the soft tissue debridement. In some instances, adequate debridement will result in flap coverage being needed for ultimate wound clo-sure. In any case, wound closure cannot be completed until adequate debridement has thoroughly been established. This may or may not require more than one debridement. DeLong et al. showed that primary closure of open frac-ture wounds is possible in some circumstances (25). Other authors (6) advocate leaving all wounds open for a time to protect against the development of significant anaerobic infection. By returning to the operating several days later for delayed primary closure, Zalavras and Patzakis felt that tissues could again be inspected and debrided while avoiding potential Clostridial infection. Experience with open fracture management may ultimately be the best determinant in decisions regarding wound closure.

In cases where the wound is not closed after primary debridement, the antibiotic bead pouch has been shown to reduce the rate of infection in compound fractures (26, 27). By mixing antibiotic (typically an aminoglycoside) with polymethylmethacrylate and forming small spherical beads on a wire (usually 24 or 26 gauge), the local delivery of antibiotics can be enhanced. After placing the beads at the fracture site, a sterile adherent self-sealing dressing is applied. The beads then elute significant concentrations of the antibiotic directly at the contaminated wound site.

As an alternative (particularly when wounds appear clean), vacuum-assisted closure (VAC) may be utilized at the ini-tial surgical procedure (28). By applying a VAC dressing, sterile conditions at the wound site can be maintained and the accumulation of local fluid collections can often be

avoided. In some cases, the resultant proliferative granu-lation tissue may transform a wound (which previously would have required a flap) into one which can be managed with skin grafting or healing by secondary intention.

In cases where tissue transfer will be necessary in order to facilitate wound closure, the literature has shown it to be beneficial to flap wounds acutely. Godina (29) found better results in 532 patients with open fractures amongst those who received their free flap within 72 hours of presenta-tion. Similarly, Gopal et al. (30) found a five-fold reduction in infection in those patients who had their open fractures fixed and flapped within the same 72 hour window. Clearly once a clean wound is established via adequate debride-ment, timely closure is important to prevent the develop-ment of nosocomial infection.

The Mangled Extremity

Perhaps the most difficult decision facing the orthopaedic trauma surgeon can be the decision to amputate a mangled extremity acutely. In cases of life threatening hemody-namic instability, an abrupt amputation may be required to preserve vitality. However, in many cases the overall situ-ation is less serious. Multiple scoring systems have been developed in an attempt to aid the treating surgeon with the decision-making process (31-35). The Mangled Extremity Severity Score (MESS) is the most commonly used aid in today’s clinical practice. These scores should function only as rough guides to help assist with this difficult decision. In a prospective study by Bosse et al. (36), the clinical utility of all lower extremity injury severity scores studied were not validated. In fact, particularly above the amputation threshold, the indices had low sensitivity. In many cases, with appropriate time and counseling, patients themselves will come to understand that amputation will return them to the highest level of function possible.

ANTIBIOTICS

The initial goal in the treatment of an open fracture is the prevention of infection. Antibiotics have been shown to markedly decrease infection rates in open fractures (37). As such, all open fractures should be treated with systemic antibiotics as early as possible. As stated previously, the use of antibiotics for open fractures should be conceptualized as therapeutic not prophylactic. There is no role for wound cul-tures in the initial management of open fractures (38). Instead antibiotics are chosen based on the nature of the wound. Adequate coverage of both gram positive and gram negative organisms is required, particularly in larger wounds. In the case of barnyard injuries or those grossly contaminated with

The initial management of open fractures

27

soil, anaerobic coverage must be provided as well. Because of the devastating consequences of the tetanus neurotoxin, all patients presenting with open fractures must be certain to have their tetanus status updated.

Although more recently newer antibiotics such as the flouroquinolones have been investigated in the use of open fractures (39), traditionally a first generation cephalosporin would be given to all patients based on the work of Patzakis et al. (37). In larger wounds, including some grade II and all Grade III fractures this would be supplemented with gram negative coverage, usually an aminoglycoside. Most recently single daily dosing of gentamicin was shown to be as effective as divided dosing in the treatment of open fractures (40). Lastly, in cases where anaerobic infection is a significant concern, penicillin can be administered to provide appropriate coverage.

As previously discussed, systemic antibiotic coverage may be supplemented with the use of local antibiotic administra-tion as well. Antibiotic bead pouches have been demonstrated to be efficacious in the clinical setting (26, 27). In the future, newer antibiotic impregnated implants and antibiotic-laden bone grafting materials may provide additional assistance in the prevention of infection in open fractures.

SUMMARY

The initial assessment of the patient with an open fracture begins with standard ATLS protocol. Once other life-threat-ening injuries have been appropriately addressed, focused management of the fracture itself should be centered on the prevention of infection and soft tissue management. This may best be accomplished by the expedient administration of properly chosen systemic antibiotics combined with emer-gent irrigation, liberal debridement and adequate skeletal stabilization. Bead pouches can provide another source of antibiotic administration, while VAC dressings may maintain sterility while definitive reconstruction is planned. Finally, timely soft tissue coverage of adequately debrided wounds will optimize functional outcomes following open fractures.

KEY WORDS

Open fracture, infection, timing, management, compound fracture, antibiotic, irrigation, debridement

REFERENCES

1. Tscherne H, and Oestern HJ. Die Klassifizierung des Weichteilschadens bei offenen und geschlossen Frakturen. Unfallheilkunde 1982;85:111-115.

Figure 1. Clinical examples of the types of open fractures according to the Gustilo classification. This is the most widely utilized system today and has been shown to provide prognostic significance

Type I Distal Tibia Fracture

Type II Open Tibial Plateau Fracture -s/p spanning external fixation

Type III Tibial Pilon Fracture

2. Gustilo RB, and Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: Retrospective and prospective analyses. J Bone Joint Surg 1976;58:453-458.

3. Gustilo RB, Mendoza RM, and Williams DN. Problems in the management of type III (severe) open fractures: A new classi-fication of type III open fractures. J Trauma 1984;24:742-746.



4. Caudle RJ, and Stern PJ. Severe open fractures of the tibia. J Bone Joint Surg 1987;69-A:801-807.

5. Brumback RJ, Jones AL. Interobserver agreement in the classification of open fractures of the tibia. The results of a survey of two hundred and forty-five orthopaedic surgeons. J Bone Joint Surg 1994;76(8):1162-1166.

6. Zalavras CG, and Patzakis MJ. Open Fractures: Evaluation and Management. J Am Acad Orthop Surg 2003;11:212-219.

7. Bednar DA, Parikh J. Effect of time delay from injury to primary management on the incidence of deep infection after open fractures of the lower extremities caused by blunt trauma in adults. J Orthop Trauma 1993;7(6):532-535.

8. Harley BJ, Beaupre LA, Jones CA, et al. The effect of time to definitive treatment on the rate of nonunion and infection in open fractures. J Orthop Trauma 2002;16(7):484-490.

9. Lineaweaver W, McMorris S, Soucy D, et al. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg 1985;75(3):394-396.

10. Kaysinger KK, Nicholson NC, Ramp WK, et al. Toxic effects of wound irrigation solutions on cultured tibiae and osteo-blasts. J Orthop Trauma 1995;9(4):303-311.

11. Gross A, Cutright DE, and Bhaskar SN. Effectiveness of pul-sating water jet lavage in treatment of contaminated crushed wounds. Am J Surg 1972;124:373-377.

12. Brown LL, Shelton HT , Bornside GH, et al. Evaluation of wound irrigation by pulsatile jet and conventional methods. Ann Surg 1978;187:170-173.

13. Adili A, Bhandari M, and Schemitsch EH. The biomechan-ical effect of high-pressure irrigation on diaphyseal fracture healing in vivo. J Orthop Trauma 2002;16(6):413-417.

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29

ROLE OF THE GUT IN SIRS

Ernest E. Moore, MD; Jeffrey L. Johnson, MD; David J. Ciesla, MD; Aaron M. Cheng, MD; and Eric L. Sarin, MD

Department of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, Denver, CO


POSTINJURY SHOCK INDUCES DISPROPORTIONATE SPLANCHNIC HYPOPERFUSION

Mechanical injury and associated hemorrhagic shock trigger a cascade of proinflammatory reactions, manifesting clini-cally as the systemic inflammatory response (SIRS), that primes the innate immune system such that a secondary insult during this vulnerable window provokes an unbridled inflammatory response culminating in multiple organ failure (MOF) (1-3). Simultaneously, the injury initiates events resulting in a depressed adaptive immune response, com-pensatory antinflammatory response (CARS), that renders the patient at risk for overwhelming infection, which can result in delayed MOF (4). While previously thought that the defective adaptive immune response in CARS was a reaction to the hyperactive innate immune response, Mannick et al. (5) have recently shown convincing proof that both derange-ments stem from the initial injury. Our interests have focused on defining which components of the initial insult (shock, tissue disruption, blood transfusion, and genetic predisposi-tion) are responsible for the dysfunctional innate immune response that sets the stage for MOF (Figure 1). Specifically, we have investigated the mechanisms critical for early priming of the innate immune system and have employed the circulating PMN as a surrogate for this response (6, 7). Our previous work has documented that injured patients at risk for MOF have a remarkably consistent pattern of postin-jury PMN priming; beginning within 2 hr. of injury, peaking at 6-12 hr., and resolving by 24 hr (8, 9).

POSTINJURY SHOCK INDUCES DISPROPORTIONATE SPLANCHNIC HYPOPERFUSION

Circulatory shock has been consistently identified as a major risk factor for postinjury MOF (10). The gut has been invoked as the mechanistic link between shock and MOF; i.e., the “motor of MOF” (11). The gastrointestinal

Figure 1. The two-event construct of early postinjury MOF is based on priming of the innate immune system.

(GI) mucosa provides a remarkably effective barrier to the potentially toxic contents of the GI tract, including a myriad of digestive enzymes and bacteria as well as their byproducts. This protection is accomplished via complex interactions between nonimmunologic and immunologic systems within the gut (12). The splanchnic organs rep-resent only 5% of the total body mass, but receive up to 30% of the cardiac output under normal conditions. The mucosal –submucosal region of the villus, the primary site for absorption, is the target for 70% of this blood flow (13). The gut barrier, however, is exquisitely vulnerable to postinjury shock because of adaptive prioritization of the systemic over mesenteric needs, i.e., blood flow is diverted from the gut to the brain, heart, kidneys, and skeletal muscle in response to circulatory shock architecture of the intestinal villus is uniquely precarious because it is sup-plied by a single arterial vessel that arborizes at the villus tip into a network of surfaces capillaries emptying into a central venule. This arrangement permits villous counter-current exchange; i.e., shunting of oxygen from the nutrient arteriole to the draining venule (14).

Following hemorrhagic shock, there is selective vaso-constriction of the intestinal inflow arterioles mediated



predominantly via the renin-angiotension system (15). But despite restoration of central hemodynamics, there is generalized persistent vasoconstriction at all levels of the intestinal microvasculature due to the net effect of multiple agents, including endothelial derived factors and circu-lating vasoactive substances (16, 17). Xanthine oxidase is generated during ischemia from its precursor xanthine dehydrogenase which is expressed constitutionally. With mesenteric reperfusion and the availability of oxygen, xan-thine oxidase rapidly produces superoxide and secondary oxygen free radicals, which can promote inflammation directly through calcium ions, or indirectly via upregulation of endothelial surface adhesion molecules and subsequent interaction with blood cell elements (18, 19). Moreover, ischemia/reperfusion upregulates a number of potentially cytotoxic intracellular pathways such as oxidant and nitro-active stresses, poly (ADP-ribose synthetase (PARS) (20). A gradient of injury evolves from the most superficial layer of the bowel wall (mucosa) to the deeper layers (muscularis propria) depending on the magnitude and duration of shock. The villus is particularly susceptible to mucosal injury due to the countercurrent diffusion of oxygen at the base and higher concentrations of xanthine oxidase in the villus tip (16). The villus is a repository of immunologically active cells, including macrophages, T lymphocytes, B lympho-cytes, mast cells, and eosinophils as well as Paneth and intestinal epithelial cells (12).

POSTSHOCK MESENTERIC LYMPH IS THE CONDUCT FOR GUT-DERIVED MEDIATORS OF SIRS

Recognition of the vulnerability of the gut due to splanchnic hypoperfusion following hemorrhage shock stimulated investigators to originally focus on gut bacterial transloca-tion as the link between postshock mesenteric I/R and distant organ injury (Figure 2). While this was an enticing concept based on severe injury models in rodents, failure to document bacteria or endotoxin in the portal circulation of critically injured patients at risk for MOF prompted us to challenge barrier failure as the unifying concept (21). In 1998, Deitch et al. (22) reported the profound observation that ligation of the mesenteric duct in rodents prevented acute lung injury following trauma/hemorrhagic shock (trauma/HS). Subsequent studies by the New Jersey group (23-27) and our group (28-35) have confirmed that post shock mesenteric lymph (PSML) can prime neutrophils (PMN) and activate endothelium in vitro. But identification of the culprit toxic factors in postshock mesenteric lymph remains a critical step for translation of these new concepts to the bedside.

Mesenteric lymph represents a delta collecting diverse byproducts from the gut and, thus, provides an opportune

site to interrogate the mechanisms linking post-ischemia gut inflammation and remote organ injury. The intestinal lymph circulation consists of two compartments, the mucosal-submucosal lymph system and the muscular lymph system, which join together near the mesenteric vascular arcade. The mucosal-submucosal lymph system drains the absorbed nutrients and metabolic by-products from the intestinal villi (36). While the villus lymph channels do not have smooth muscle cells, the intestinal muscular mucosa lines the villi beneath the epithelium and contracts in syn-chrony with relaxation of the muscular layers of the gut to propel lymph from the villi (37). The collecting outflow lymph vessels are lined with endothelial cells and smooth muscle cells and have rhythmic contractions with undirec-tional values to prevent retrograde lymp flow. The enteric nervous system also plays an important role in coordinating villus contractions and, thus, regulating lymph flow (38).

The proinflammatory response induced by mesenteric I/R is complex, and the process whereby local gut events translate into distant organ injury remains unclear. Tissue ischemia, and subsequent oxidant stress with reperfusion, activates families of protein kinases; e.g., mitogen – acti-vated protein kinases that converge on transcription factors, e.g., NF-kB, C/EBPβ and AP-1 that regulate the expres-sion of inflammatory genes (39, 40). Recent work suggests hypoxic – inducible factor – 1 (HIF-1α) may play an impor-tant role (41). The resultant proinflammatory gene products include cytokines (TNFα, IL-1β, IL-6), chemokines (IL-8), adhesion molecules (ICAM-1), and enzymes (inducible nitric oxide synthase, phospholipase A2). These agents ini-

Figure 2. The role of the gut in the pathophysiology of postinjury MOF is complex, but there is growing evidence that mesenteric lymph conveys the culprit inflammatory mediators.

Role of the gut in sirs

31

tiate local inflammation which is further amplified by the recruitment and activation of PMNs. Mesenteric I/R also induces anti-inflammatory genes for cytokines (IL-10) and protective enzymes (hemeoxygenase -1, cyclooxygenase-2) to presumably control local injury (42-44). Deitch et al (45) have suggested the gut is a “cytokine-generating organ” based on their hemorrhagic shock experiments in rodents. Elevated circulating levels of TNFα, IL-1β, and IL-6 have been documented in several animal studies, (46-48) and TNFα and IL-1B are generated from ischemic human small bowel (49). In case reports of patients with MOF, thoracic duct sampling has shown increased lymph: plasma levels of IL-1β, IL-6 and IL-10 (50-52).

We have had a long-term interest in lipid mediators as the mechanistic link between splanchnic ischemia and remote organ injury (53, 54) Phospholipase A2 (PLA2) is a well-described proximal enzyme in the generation of proinflam-matory lipids invoked in the pathogenesis of a number of hyperinflammatory processes (55, 56). Circulating PLA2 levels have correlated with the incidence of MOF in clinical studies of injured patients as well as sepsis. Further, PLA2 is highly concentrated in the gut and its calcium activation domain is believed sensitive to oxidant stress. We were one of the first groups to demonstrate that mesenteric I/R activates gut PLA2 (Figure 3) and ultimately showed that a PLA2 inhibitor decouples gut I/R from producing acute lung injury (54). Remarkably even initiating treatment after reperfusion proved effective, suggesting that the combina-tion of activated PLA2 isoforms with substrate availability and the restoration of lymph flow are pivotal in the patho-genesis of remote organ. Consequently, we hypothesize

that the predominant proinflammatory agents in postshock mesenteric lymph are lipid molecules, generated by initial PLA2 activity. Diverse isoforms of PLA2 are clinically rel-evant to the injured patient (Figure 4). PLA2 catalyzes the hydrolysis of the sn-2 position of phospholipids to generate arachidonic acid (AA) and lysophospholipids. The three major classes of PLA2 are cytosolic (cPLA2), calcium inde-pendent (iPLA2), and secretory (sPLA2); there are at least 19 mammalian isozymes of PLA2. Proinflammatory eico-sanoid generation by sPLA2 may be modulated by cPLA2. Secretory PLA2s hydrolyze the sn-2 position of phospho-lipids in the presence of nM of calcium with no strict fatty acid specificity. We and others have documented elevated circulating levels of sPLA2 in severely injured patients at risk for MOF (57). We have also recently documented the M type sPLA2 receptor on human PMNs (58). There are several isozyme candidates from the sPLA2 family that may be involved in the generation of proinflammatory agents in mesenteric lymph. sPLA2 – IB is synthesized in the pan-creatic acinar cells and excreted into the pancreatic juice; it also has high affinity for the M type sPLA2 receptor. Thus, the pancreas, which is exquisitely sensitive to splanchnic hypoperfusion, may be a significant contributor to PSML cytotoxicity. sPLA2 – IIA is well recognized in exudative fluids associated with inflammatory processes. sPLA–IIA is induced readily by a number of proinflammatory stimuli, and the promoter region of the sPLA–IIA gene contains binding sites for several transcription factors including NF-kB, C/EBPβ, and AP-1. sPLA–IIA binds weakly to the sur-face of resting cells but, in activated cells, it is shuttled via a caveolin-rich vesicular system (HSPG-shuttling pathway) to a perinuclear compartment where there are arachidonic acid (AA) metabolizing enzymes including 5 lipoxygenase. Koike et al. (59) reported that a sPLA–IIA inhibitor (S5920/

Figure 3. The reperfused mesenteric circulation serves as a priming bed for circulating PMNs that provoke distant organ injury following secondary activation. Gut PLA2 activation is a key proximal step, occurring during ischemia, and PMN CD11b/CD18 dependent interaction with pulmonary endothelium is a critical distal event.

Figure 4. Lipids can provoke PMN priming via a number of metabolic byproducts.



LY315920Na) prevented acute lung injury following gut I/R in the rat. sPLA–IID, structurally similar to sPLA2–IIA, is expressed constitutively in digestive organs, upregulated by proinflammatory stimuli, and augments cellular AA via a caveolin–rich system. sPLA2–IIE is another sPLA2-IIA related enzyme and share several of the features outlined for sPLA2-IID. In contrast to the heparin-binding group II sPLA2 enzymes, sPLA2-V and sPLA2-X can act on the PC-rich outer plasma membrane to release AA which may be transported subsequently across the cytosol to perinuclear 5-LO and COX. Finally, sPLA2-XII (19kDA) has been identified in human pancreas. Presuming that PLA2 may become activated too early postinjury to access therapeuti-cally, the next level of enzyme activity to consider includes cyclooxygenases (COX) and lipoxygenases (LO) that cata-lyze the insertion of molecular oxygen into various posi-tions in AA. COX1 is constitutively expressed throughout the gastrointestinal tract and has been suggested to maintain mucosal integrity, while COX2 is induced predominantly during inflammation (60-62). Although COX2 inhibitory agents have been used to treat inflammatory bowel disease, recent evidence suggests that COX2 induction protects ischemic gut via the release of prostaglandins (PGE2 and PGI2). The proinflammatory lipids in PSML could be lipoxygenase derived. The lipoxygenase (LO) system con-sists of three primary pathways: 5-LO, 12–LO, and 15-LO (63, 64). 5-LO metabolizes AA to 5-hydroperoxyeicosatet-raenoic acid (5-HPETE) which is dehydrated into LTA4. LTA4 is a highly unstable epoxide which is enzymatically hydrolyzed (LTA4 hydrolase) into LTB4 or conjugated with reduced glutathione (LTC4 synthase) to form LTC4. LTB4 is one of the most effective chemotactic agents produced by leukocytes and LTC4 is a potent constrictor of arterioles and increases permeability of the postcapillary venules (65-68). 5-LO activating protein (FLAP) is a membrane associated protein critical in leukotriene metabolism. 5-LO and FLAP are highly expressed in PMNs, monocytes, and macrophages. The actions of LTB4 are mediated via at least two distinct G protein –coupled receptors, referred to as BLT1 and BLT2 (69, 70). BLT2 is expressed ubiquitously, while BLT1 is expressed primarily on leukocytes. The liver serves as the principal site for LTB4 clearance from the systemic circulation, where the hepatic P450 enzyme (CYP4F2) metabolizes LTB4 to its omega – hydroxylated metabolite 20 hydroxylleukotriene B4 (20-OH LTB4), which is subsequently carboxylated (20-C00H LTB4) (71).

More than 30 years ago Tilney et al. (72) recognized sequen-tial organ failure after rupture of abdominal aortic aneu-rysms, and identified the pancreas as the most susceptible organ. Subsequently, the ischemic pancreas was incrimi-nated as the source for a circulating myocardial depressant

factor following hemorrhagic shock (73, 74). There has been renewed interest in the pathophysiologic role of the pancreas in postinjury MOF (75, 76). Specifically there is emerging evidence that the release of pancreatic enzymes into the intestinal lumen is important in the genesis of post-shock gut proinflammatory agents (77). Two independent groups of investigators (78, 79) have recently demonstrated that inhibiting pancreatic enzymes within the intestinal lumen prevents hemorrhagic shock induced MOF in vivo. Thus, the ischemic pancreas may function cooperatively with the ischemic intestine by providing a source of acti-vated enzymes that interact with substrate in the intestine to generate bioactive lipids in the mesenteric lymph.

While the transcellular pancreatic intestinal PLA2 enzyme cascade hypothesis for the generation of bioactive lipids is an enticing unifying concept, it may be incorrect. There has been recent interest in the role bioactive phospholipids oxidation products in promoting inflammation particularly in the pathogenesis of atherosclerotic lesions (80, 81). Of interest, oxidatively fragmented phospholipids have been shown to bind and active the human PAF receptor (82). Further, these bioactive phospholipids are less susceptible to hydrolysis. These recent observations may explain our earlier bench and clinical studies that invoked PAF as a key gut-derived mediator of postshock MOF (84). Finally, it is conceivable that both intestinal/pancreatic enzymes and oxidation of gut phospholipids are critical in the genesis of bioactive PSML. For example, sPLA2 is suggested to promote atherosclerosis via liberating the substrate for pathologic oxidized phospholipids (85).

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71. Jin R, Koop, D Raucy J et al. Role of Human CYP4F2 in Hepatic catabolism of the proinflammatory agent leukotriene B4. Arch Biochem Biophys, 1998; 359: 89.


35

72. Tilney, NL, Gailey, GL, and Morgan, AP: Sequential system failure after rupture of abdominal aortic aneu-rysms: An unsolved problem in postoperative care: Ann Surg 1973; 178:2.

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76. Schmid-Schonbein, GW, Hugli, TE, Kistler, EB et al: Pancreatic enzymes and microvascular cell activation in multiorgan failure. Microcirculation 2001;8:5.

77. Deitch, EA, Shi, HP, Lu, Q et al: Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury. Shock 2003; 19:452.

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36

HYPERTONIC SALINE – CONFLICTING DATA

David B. Hoyt, MD, FACS

University of San Diego, Medical CenterSan Diego, California


In designing a resuscitation strategy that is beneficial it is important to recognize that certain lethal injuries can be defined. These include severe head injuries, life threatening airway injuries, significant chest injuries to the heart and great vessels with exsanguination, massively disruptive abdominal visceral injuries with exsanguination and injuries with signifi-cant exsanguinating retroperitoneal bleeding such as massive pelvic fractures. Resuscitation aimed at these patients will unlikely be associated with improved outcomes.

When one reviews the development of trauma systems and the effects of fluid resuscitation, it is difficult to evaluate the data. Reports vary by where death occurs (in the field, in the hospital, or in the operating room) and it is also difficult to sort out the effects of transport times, the presence of airway control and ventilation, the type and degree of fluid resusci-tation or use of MAST suits, and the impact of surgery.

The first true useful study that identified the timeliness of care relative to bleeding came from the Birmingham Accident Hospital in 1968 (1). Sevitt demonstrated in review of 250 patients over 5 years that 28% of patients died in less than 6 hours and this was the first indication of patients who were bleeding to death rapidly. This suggested that early fluid resuscitation for bleeding has to be focused on the earliest outcomes, and that when you bleed enough to die you do so in less than 6 hours.

An epidemiologic evaluation of traumatic deaths following trauma system implementation in San Diego reveals the majority of patients die within 6 hours from exsanguination (2). An almost identical study from Denver identified the critical time of 6 hours for death from exsanguination (3).

SHOULD WE RESUSCITATE

Canon pointed out the disadvantage fluid resuscitation in 1910 and emphasized that increases in blood pressure prior

to surgical hemostasis would “pop the clot” and increase bleeding with potential exsanguination. This has led to much controversy over fluid resuscitation in injured patients (4).

WHAT WE HAVE LEARNED

• There are certain injuries that will be deadly and refrac-tory to fluid therapy care.

• Excessive fluid resuscitation prior to surgical hemo-stasis will be accompanied by increased bleeding

• Patients who are bleeding will exsanguinate immedi-ately or stop bleeding spontaneously at approximately 6 hours.

WHICH FLUID?

Resuscitation strategies recently have focused on concerns regarding the use of Ringer’s lactate, the reemergence of the evaluation of hypertonic saline, the use of colloids, the use of alternative crystalloids, and the use of oxygen car-rying solutions or hemoglobin solutions.

A recent report of the Institute of Medicine raised concerns with crystalloid resuscitation using Ringer’s lactate and con-cerns have been raised regarding colloid resuscitation (5).

Increasingly, hypertonic saline has been attractive and is able to achieve higher pressure resuscitation for equiva-lent volumes and may have an immuno-modulatory role. Hypertonic saline (7.5%) is currently not FDA approved.

The advantages of hypertonic saline resuscitation include its hemodynamic effects, its effects on lowering ICP in brain injured patients, and most recently multiple studies which have suggested benefits in modulating the inflammatory response. Concerns have been raised about the effects of enhanced blood pressure restoration using hypertonic saline and the effect on primary hemostasis (6). Recent data sug-gests in a well designed animal model that retroperitoneal bleeding is less following HTS resuscitation with less per-

Hypertonic saline – Conflicting data

37

cent bleeding. Although concern has been raised regarding aggravation of bleeding, this recent study suggests this is not a significant problem. As such, hypertonic saline should be evaluated (7).

The advantages of hypertonic saline in head injury have been recently reviewed (8). It is clear that in animal models HTS decreases intracranial pressure, and prevents the intracranial pressure increases that follow shock. These changes occur primarily in areas of the brain that maintain intact blood brain barriers. Human studies have been few in number in head injury and a uniform concentration has not been studied. It does appear, however, that the use of hypertonic saline is accompanied by a reduction in intracranial pressure and that this is particularly beneficial in children (9).

HTS IMMUNOLOGIC CHANGES

The discovery of the immunologic properties of hypertonic saline occurred following observations of immunosuppres-sion in in vitro T-cell blastogenesis by high extracellular salt concentrations (10). Subsequent analysis revealed that lower concentrations achievable clinically, were immuno stimulatory.

Much work by many groups has evaluated the mechanisms in a variety of cells. Significant observations include the ability to reduce organ dysfunction and improve survival in animal models including hemorrhage and subsequent infec-tion following hypertonic saline resuscitation (11, 12). The mechanisms by which this occurs have been explored in great detail. There appears to be a membrane associated effect of hypertonic saline leading to activation of protein tyrosine kinases (essential intracellular second messengers) which lead to nuclear activation protein synthesis, and proliferation (13-15). The timing of HTS is important.

The mechanism of hypertonic saline on polymorphonuclear leukocyte function appears to be multifactorial but impor-tantly adhesion to the microcirculation is significantly different between hypertonic saline and Ringer’s lactate and this is accompanied by decreased adhesion molecule expression and reduced organ failure in animal models. It appears that the restoration of adhesion molecule regula-tion can occur if the osmotic environment is normalized and be reestablished by giving a second dose or recreating the hypertonic environment (16, 17). This suggests that the manipulation of resuscitation fluids may, in fact, be much like dosing a drug and establishes the research need for further exploration in the future. Recent data suggests that direct involvement of hypertonic environments with the cytoskeleton and the induction of cytoskeletal polymeriza-

tion is a fundamental mechanism by which adhesion mol-ecule expression and oxidative injury are affected (18, 19).

Human studies have shown preliminary evidence that immune variables demonstrated in animals can be dem-onstrated following infusion to human volunteers (20). Previous multicenter trials, however, comparing Ringer’s lactate and hypertonic saline with Dextran were unable to show overall differences in survival. Of interest, however, there was a survival advantage in patients who required surgery and it would appear that the hypertonic saline Dextran group had fewer complications (21). A multicenter trial looking at patients transported by helicopter suggested a mortality advantage in head injured patients.

One can conclude from the data to date that from basic research data there appears to be improved microvascular flow, less organ dysfunction, and in some uncontrolled bleeding models there is no exaggeration of bleeding. That hypertonic saline controls intracranial pressure and brain edema and has immunomodulatory value is also clear. When one looks at clinical applicability, there are currently no good studies of the infectious or inflammatory compli-cations that might be affected by hypertonic resuscitation. The only demonstrated mortality advantage has been in head injured patients. Given the important new information that has occurred in the last 10 years, it is critically impor-tant that these fluids be reevaluated in clinical trials.

REFERENCES

1. Sevitt S: Fatal road accidents. Brit J Surg 55(7):481-505, 1968.

2. Shackford SR, Mackersie RC, Holbrook TL, et al: The epide-miology of traumatic death. Arch Surg 128:571-575, 1993.

3. Sauaia A, Moore FA, Moore EE, et al: Epidemiology of trauma deaths: a reassessment. J Trauma 38(2):185-193, 1995.

4. Bickell WH, Wall Jr. MJ, Pepe PE, et al: Immediate versus delayed fluid resuscitation for hypotensive patients with pen-etrating torso injuries. N Engl J Med 331:1105, 1994.

5. Pope A, French G, Longnecker DE (Eds): Fluid Resuscitation. State of the Science for Treating Combat Casualties and Civilian Injuries. National Academy Press, Washington, D.C., 1999.

6. Matsuoka T, Hildreth J, Wisner DH: Uncontrolled hemor-rhage from parenchymal injury: Is resuscitation helpful? J Trauma 40(6):915-921, 1996.

7. Cruz RJ, Perin D, Silva LE, et al: Radioisotope blood volume measurement in uncontrolled retroperitoneal haemorrhage induced by a transfemoral iliac artery puncture. Injury 32(1):17-21, 2001.



8. Doyle JA, Davis DP, Hoyt DB: The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma 50(2):367-383, 2001.

9. Pfenninger J, Wagner BP: Hypertonic saline in severe pedi-atric head injury. Crit Care Med 29(7):1489, 2001.

10. Junger WG, Liu FC, Loomis WH, Hoyt DB: Hypertonic saline enhances cellular immune function. Circ Shock 42:190-196, 1994.

11. Coimbra R, Hoyt DB, Junger WG, et al: Hypertonic saline resuscitation decreases susceptibility to sepsis following hemorrhagic shock. J Trauma 42(4):602-607, 1997.

12. Rizoli SB, Kapus A, Parodo J, et al: Immunomodulation is reversible and accompanied by changes in CD11b expres-sion. J Surg Res 83(2):130-135, 1999

13. Junger WG, Herdon-Remelius C, Junger H, et al: Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and acti-vating mitogen-activated protein kinase p38. J Clin Invest 101(12);2768-2779, 1998.

14. Rizoli SB, Kapus A, Parodo J, Rotstein OD: Hypertonicity prevents lipopolysaccharide-stimulated CD11b/CD18 expres-sion in human neutrophils in vitro: role for p38 inhibition. J Trauma 46 (5):794-798, 1999.

15. Ciesla DJ, Moore EE, Biffl WL, et al: Hypertonic saline activation of p38 MAPK primes the PMN respiratory burst. Shock 16(4):285-289, 2001.

16. Ciesla DJ, Moore EE, Biffl WL, et al: Attenuation of the neutrophil cytotoxic response is reversed upon restoration of normotonicity and reestablished by repeated hypertonic challenge. Surgery 129(5):567-575, 2001.

17. Ciesla DJ, Moore EE, Zallen G, et al: Hypertonic saline attenuation of polymorphonuclear neutrophil cytotoxicity: time is everything. J Trauma 48(3):388-395, 2000.

18. Rizoli SB, Rotstein OD, Parodo J, et al: Hypertonic inhibi-tion of exocytosis in neutrophils: central role of osmotic actin skeleton remodeling. Am J Physiol Cell Physiol, 279(3):C619-C633, 2000.

19. Ciesla DJ, Moore EE, Musters RJ, et al: Hypertonic saline alteration of th PMN cytoskeleton: Implications for signal transduction and the cytotoxic response. J Trauma 50(2):206-212, 2001.

20. Angle N, Cabello-Pasini R, Hoyt DB, et al: Hypertonic saline infusion: Can it regulate human neutrophil function? Shock 14(5):503-508, 2000.

21. Mattox KL, Maningas PA, Moore EE, et al: Prehospital hypertonic saline/dextran infusion for post-traumatic hypo-tension. A U.S.A. Multicenter Trial. Ann Surg 213(5):482-491, 1991.

39

LIVER WRAPPING, PACKING & HEMOSTATICS

Kimball I. Maull, MD, FACS

Carraway Medical CenterBirmingham, Alabama


INTRODUCTION

With advances in technology, diagnostic interventions and intensive care, management of most patients with liver injuries is now non-operative. Many Grade 4 liver injuries are successfully managed without operation and the fig-ures quoted in the recent literature confirm that >90% of patients with injuries to the liver can be approached without operation (1). The early use of angiographic embolization may further enhance these statistics in favor of avoiding operation (2). Critical and supportive care remain essential to enable a successful outcome.

The trend toward non-operative management has led to the recognition that, when operation is required for liver injury, it is often an exsanguinating injury challenging the tech-nical abilities of the operating surgeon. Mortality exceeds 50% for patients managed by hepatic lobectomy for acute parenchymal injury, and survivors are few among those requiring the placement of atriocaval shunts for retrohe-patic injuries. This report will describe both the laboratory and the clinical experience with external liver wrapping and internal liver packing as adjuncts in the control life-threat-ening liver hemorrhage. Recent advances in hemostatics, used in combination with intrahepatic liver packing, show great promise in further reducing mortality.

EXPERIMENTAL AND CLINICAL STUDIES

Tamponade of liver bleeding may be classified as external or internal. The simplest form of external tamponade is that provided at operation by manual compression as one seeks to control the hemorrhage prior to determining actual sites of bleeding. If bleeding persists despite traditional tech-niques of hemostasis (suture, debridement, cautery, etc), it is common practice to place packs around the liver to compress bleeding sites. This technique of external hepatic

tamponade, when applied correctly, is often effective in controlling bleeding, but requires a second operation for pack removal and is associated with an increased incidence of peri-hepatic sepsis.

In 1992, Stevens et al described a technique for totally encompassing the liver in an absorbable mesh wrap, thereby providing a form of external hepatic tamponade which avoids the need for a second operation (3). Described first in the porcine model and used in a limited number of exsan-guinating patients, the method proved both feasible and life saving (4). A subsequent report from France confirmed the efficacy of the technique and broadened the indications for its use (5). However, the technique has not been widely adopted due a learning curve and concerns about rapidity of application.

Using the same porcine controls, Schmidt et al proved the hemostatic value of direct intrahepatic packing with absorb-able mesh (6). Further, by studying the animals sequentially, the fate and safety of the intrahepatic mesh was determined over time. The study showed that a fibrous capsule is laid down around the mesh and absorption is near complete at 6 months post packing. This form of intrahepatic tamponade has the advantage of immediate availability and sizing. Following this favorable experience in the lab, Frame et al in 1995 reported a clinical series from the same institution (7). Twelve patients with severe liver injuries were packed with absorbable mesh and ten survived. Both deaths were in patients with Grade 5 injuries involving the retrohepatic vena cava. Long term follow-up of the survivors confirmed the safety and efficacy of the technique.

More recently, Holcomb et al have combined intrahepatic mesh packing with the use of fibrin sealant (8). By impreg-nating the mesh with lypholized thrombin, calcium and fibrinogen, the tamponade effect is enhanced by an acceler-ated coagulation reaction which is activated by moisture from the wound. This dry fibrin dressing has been studied in a standardized porcine model in which reproducible severe



injuries were created. More recently, the technique has proven successful in a “damage control” model, using the same anatomic injury but allowing the animal to become hypothermic and coagulopathic prior to placing the intrahe-patic packs (9). A comparison study with other varieties of hemostatics confirmed the benefit of this dressing (10). It is currently being used clinically in the military.

CONCLUSIONS

Most injuries to the liver can be successfully managed non-operatively. For those requiring operative control of liver bleeding, the placement of intrahepatic absorbable mesh packing impregnated with dry fibrin sealant shows great promise for controlling hemorrhage even in severe parenchymal liver trauma.

REFERENCES

1. Maull, K. I.: Current status of non-operative management of liver injuries. World Journal of Surgery 25:1403-1404, 2001.

2. Wahl, W.L., Ahrns, K.S., Brandt, M.M. et al: Need for early angiographic embolization in blunt liver injuries. Journal of Trauma 52:1097-1101, 2002.

3. Stevens, S.L., Maull, K.I. & Enderson, B.L.: Total hepatic mesh wrap for hemostasis. Surgery, Gynecology & Obstetrics. 175: 181 - 82, 1992.

4. Stevens, S.L., Maull, K.I., Enderson, B.L., et al.: Total mesh wrapping for parenchymal hepatic injuries -- a com-bined experimental and clinical study. Journal of Trauma 31(8):1103-1109, 1991.

5. Brunet, C., Sielezneff, I., Thomas, P. et al: Treatment of hepatic trauma with perihepatic mesh: 35 cases. Journal of Trauma 37:200-204, 1994.

6. Schmidt, U., Maull, K.I., Enderson, B.L., et al. Intrahepatic absorbable packing for exsanguinating liver injuries. Panamerican Journal of Trauma 3:106-109, 1992.

7. Frame, S.B., Enderson, B.L., Schmidt, U., and Maull, K.I.: Intrahepatic absorbable fine mesh packing of hepatic inju-ries: a preliminary clinical report. World Journal of Surgery 19:575-580, 1995.

8. Holcomb, J.B., Pusateri, A.E., Harris, R.A. et al: Effect of dry fibrin sealant dressings vs gauze packing on blood loss in grade V liver injuries in resuscitated swine. Journal of Trauma 46:49-57, 1999.

9. Holcomb, J.B., Pusateri, A.E., Harris, R.A. et al: Dry fibrin sealant dressings reduce blood loss, resuscitation volume and improve survival in hypothermic coagulopathic swine with grade V liver injuries. Journal of Trauma 47:233-242, 1999.

10. Pusateri, A.E., Modrow, H.E., Harris R.A., et al: Advanced hemostatic dressing development program: animal model selection criteria and results of a study of nine hemostatic dressings in a model of severe large venous hemorrhage and hepatic injury in swine. Journal of Trauma 55:518-526, 2003.

41

SYSTEMIC INFLAMMATORY RESPONSE SYNDROME AND POSTERIOR ISCHEMIC OPTIC NEUROPATHY AFTER BLUNT TRAUMAAlfredo A Santillan, MD, MPH;1 Francisco J Agullo, MD;1 Carlos Vazquez, MD,2 Alan H Tyroch, MD, FACS1

1 Department of Surgery, Texas Tech University Health Sciences Center, El Paso, Texas.

2 Department of Ophthalmology, Texas Tech University Health Sciences Center, El Paso, Texas.


SUMMARY

We report the first case of Posterior Ischemic Optic Neuropathy (PION) in a 38-year-old Hispanic man who sustained a high-speed motorcycle crash that resulted in an open femur fracture. The patient had an estimated blood loss of 8 liters and required fluid replacement of 68 liters that resulted in abdominal compartment syndrome. On postoperative day 12, the patient was believed to have PION secondary to perioperative hypotension, systemic inflamma-tory response syndrome, microcapillary leak syndrome, and massive fluid resuscitation (>20 liters in the first 24 hours) which resulted in abdominal compartment syndrome. The precise mechanisms involved in the development of PION in trauma patients are unknown. Avoiding hypotension and anemia seem to be the optimal protection against loss of vision. Treatments focusing on increasing oxygen delivery to the optic nerve and decreasing elevated intraocular pres-sure should be evaluated in trauma patients.

Key words

Abdominal compartment syndrome, systemic inflammatory response syndrome, posterior ischemic optic neuropathy

RESUMEN

Este es el primer reporte de neuropatía óptica isquémica posterior (NOIP) en un paciente hispano de 38 años que tuvo un accidente de motocicleta resultando en fractura abi-erta de fémur. El paciente tuvo una perdida sanguínea de 8 litros y requirió 68 litros de fluído intravenoso resultando en el síndrome de compartimiento abdominal. En el día post-operativo 12, se encontró al paciente con ceguera secundaria a hipotensión peri-operatoria, al síndrome de respuesta inflamatoria sistémica, y una resucitación masiva (> 20 litros en 24 horas) ocasionando el síndrome de compartimiento abdominal. Los mecanismos que resultan NOIP en pacientes con trauma no se conocen y no se han estudiado. El evitar hipotensión y anemia son la forma ideal de proteger contra la ceguera. Tratamientos que se enfoquen al incremento de oxígeno en el nervio óptico y al disminuir la presión intra-ocular deben de ser evaluadas en pacientes de trauma con resucitación masiva en las primeras 24 horas.

Palabras clave

Síndrome de compartimiento abdominal, síndrome de respuesta inflamatoria sistémica, neuropatía óptica isquémica posterior

INTRODUCTION

Ischemic optic neuropathy (ION) is an uncommon cause of blindness most frequently seen in the elderly and is associated with diabetes, hypertension, chronic renal failure, coronary artery disease, collagen-vascular disease and infectious pro-cesses (1). The disease entity of ION involves an imbalance of oxygen supply and demand in the optic nerve that then causes damage to the nerve fibers, with consequent visual field defects that could result in blindness. This occurs in

either of two parts of the optic nerve, where the optic nerve enters the globe of the eye (anterior), or where the optic nerve lies in the orbit behind the globe (posterior) (2).

Most of what is known about anterior ischemic optic neu-ropathy (AION) is derived from studying patients who have not experienced surgery or trauma. AION has been recently recognized as an uncommon complication of hemorrhagic shock (3) and systemic inflammatory response syndrome (SIRS) in trauma patients (1). However, no association has yet been reported between posterior ischemic optic neu-ropathy (PION) and blunt trauma.

We report a patient who developed PION with bilateral blind-ness secondary to perioperative massive fluid resuscitation



after sustaining a large degloving avulsion laceration involving the soft tissues of the right anterior thigh with an open femur fracture and subsequent abdominal compartment syndrome.

CASE REPORT

A 38-year-old Hispanic man arrived as a trauma transfer after a high-speed motorcycle crash that resulted in multiple lower extremities fractures, including a large degloving avulsion laceration involving the soft tissues of the right anterior thigh and an open segmental type 3A femoral shaft fracture. In the field the patient denied loss of conscious-ness, a helmet was present, his vital signs were stable, and his Glasgow Coma Scale (GCS) score was 15. Advanced trauma life support resuscitation protocols were initiated. Given the extent of his fractures the patient was intubated prior to his transport to the trauma center. The patient was transported by helicopter, and fluid resuscitation and trans-fusion of three units of packed red blood cells were initiated en route since the patient had an episode of hypotension. Mechanical ventilation, sedation, analgesia, and traction to bilateral lower extremities were administered prior to his transport. The patient arrived to the trauma center with a heart rate of 105 bpm, blood pressure of 112/60 mm Hg, arterial oxygen saturation of 99%, a GCS score of 3 and temperature of 35.6 °C. An initial arterial blood gas showed hemoglobin of 12.7 g/dl, with a base deficit of 8.

Physical examination revealed a large degloving avulsion laceration involving the soft tissues of the right ante-rior thigh with an open segmental type 3A femoral shaft fracture, segmental closed right tibia fracture, minimally displaced right lateral tibial plateau fracture, and a right type 1 open olecranon fracture. No pulses were palpated in the right foot. Also, a left thigh contaminated laceration extending to the left femur was found in conjunction with an open type 3A comminuted left tibia fracture. A right fifth open distal phalanx fracture was also observed. The remainder of the physical examination was unremarkable. Patient injury severity score was 13. Initial laboratory data in the trauma bay showed a hematocrit of 36.4% and no evidence of coagulopathy.

Computed tomography (CT) of his head, cervical spine, abdomen and pelvis were normal. An angiogram of his lower extremities demonstrated intact femoral arteries and diminished bilateral flow to both lower extremities possibly secondary to compartment syndrome. A repeat arterial blood gas revealed a hemoglobin of 9.1 g/dl and a base deficit of 11, therefore, two units of packed red blood cells were trans-fused en route to the operating room. The patient maintained a normal blood pressure prior to his operative procedure.

Multiple procedures were performed in the operating room, including irrigation and debridement of all open fractures and lacerations, open reduction and retrograde intramed-ullary nail fixation of the open femur fracture, right thigh and leg fasciotomies, and external fixation of the right tibia fracture. Approximately 5 hours after starting these proce-dures, the patient developed anasarca, a distended and rigid abdomen, decreased urine output, and high peak airway pressures. The decision was made to stop the orthopaedic management of the lower extremities and to emergently decompress the abdominal compartment syndrome. Two liters of serous fluid were drained from the abdomen and a “Bogota bag” was placed for closure of the abdomen. The patient’s condition improved after the laparotomy and was transferred to the surgical intensive care unit.

During his intraoperative course, the patient required a total of 53 liters of crystalloids, 43 units of packed red blood cells, 2 units of fresh frozen plasma, 10 units of cryoprecipitate, 2 units of platelets, and 3 liters of colloids. Total fluid replace-ment was estimated at 68 liters, while the estimated blood loss was 8 liters, and a urine output was 3.3 liters. The lowest recorded blood pressure and temperature were 90/40 mm Hg and 35.0 °C, respectively. The most abnormal arterial blood gas values included a base deficit of 19.5 and pH of 6.97. The patient was coagulopathic and anemic with a prothrombin time of 23.4 seconds, activated partial thromboplastin time of 89.3 seconds, and a hemoglobin of 7.0 g/dl.

During the first postoperative day in the surgical intensive care unit, the patient required resuscitation with a total of 2 liters of crystalloids, 9 units of packed red blood cells, and 4 units of fresh frozen plasma to correct the anemia and coagulopathy due to a severe inflammatory syndrome associated with anasarca. During this interval increased airway pressures and a severe respiratory distress syndrome were noted, requiring high levels of inspired oxygen (FIO2 100%), and bilateral chest tubes.

During the first postoperative week, the patient under-went staged orthopaedic management of his wounds and extremity fractures while under mechanical ventilation, sedation and analgesia. On postoperative day 12, after 24 hours of being without sedation or mechanical ventilation, the patient complained of bilateral blindness. Neurology and ophthalmology consultations were obtained. Physical exam showed an absent optokinetic response, afferent pupillary defect, good extraocular muscle movements, normal corneal reflex, and blindness in both eyes. Fundoscopic examination was initially normal, however, mild disc edema occurred a few days later. CT and magnetic resonance imaging (MRI) of the head were performed and showed no evidence of

Systemic inflammatory response syndrome and posterior ischemic optic neuropathy after blunt trauma

43

brain infarction. The patient was believed to have PION secondary to perioperative hypotension that required mas-sive fluid resuscitation caused by hemorrhage and a SIRS with microcapillary leak syndrome accompanied with an abdominal compartment syndrome. The patient was dis-charged to the ward, where he continued to recover from his injuries, and few weeks later, discharged from the hospital on post-injury day 30 with complete blindness. DISCUSSION

There have been very few reports on the association between trauma and blindness (4, 5). Blindness may be caused by injury anywhere along the visual tract from the cornea to the occipital cortex. Aside from direct trauma to the visual system, loss of vision can occur after severe hypotension with ischemic damage to the parietal and occipital lobes of the brain. Nevertheless, hypotension rarely causes isch-emic damage to the optic nerves, as in ION (6, 7). Anterior ischemic optic neuropathy has been reported as a rare cause of blindness in trauma patients (1, 3, 8-14). There has only been one reported case of PION related to trauma, occurring in a patient with massive hemorrhage and severe hypoten-sion after penetrating thoracoabdominal injury (15). To our knowledge, no association has been reported between blunt trauma and PION. We report the first case of PION in a patient with bilateral blindness secondary to perioperative massive fluid resuscitation after sustaining severe blunt trauma with subsequent abdominal compartment syndrome.

ION is a rare cause of blindness that is usually associated with such entities as giant cell arteritis, systemic hyperten-sion, diabetes mellitus, chronic renal failure, advanced age, hyperlipidemia, systemic lupus erythematosus, and herpes zoster ophthalmicus (16-19). None of these risk factors were present in our patient. ION can be classified into anterior and posterior, the latter being the rarer of the two. PION consists of an infarct centered within the intraorbital portion of the optic nerve, where the nerve is more vulner-able to ischemia than are the anterior, intracanalicular, and intracranial portions (16, 20-24).

The precise mechanisms involved in the development of ION in trauma patients are unknown. The common denom-inator after trauma seems to be SIRS after profound hemor-rhagic shock and massive fluid resuscitation (>20 liters in the first 24 hours), with subsequent abdominal compartment syndrome (1). Both AION and PION can be triggered by hypotension. In AION, however, such factors as age, long-standing diabetes, and hypertension with an anatomic pre-disposition (“disk at risk”) are important (25). In contrast, a recent experimental study showed that hypotension was

the most important risk factor associated with PION (26). Despite autoregulation in the retinal arteries, blood supply in choroidal or optic nerve circulation is directly related to the arterial pressure, and less well-protected by autoregula-tion (27, 28). The posterior optic nerve is most vulnerable to ischemia between the optic foramen at the orbital apex and the point of entry of the central retinal artery (8).

Several risk factors for SIRS besides shock per se could aggravate ischemia to the optic nerve. For instance, abdominal compartment syndrome occurs frequently in patients who develop SIRS after massive fluid resuscita-tion1. The increase in intra-abdominal pressure is known to be associated with intracranial hypertension (29). Although speculative, this may compromise the optic compartment by decreasing perfusion. Furthermore, SIRS after shock and massive fluid resuscitation could also result in an ocular compartment syndrome similar to the abdominal compart-ment, which has not been described in trauma patients. The low incidence of blindness after SIRS and massive fluid resuscitation could be explained by anatomic variations that puts this population of patients at risk for ocular compart-ment syndrome. Also, hypothermia commonly develops in patients with severe trauma, shock and SIRS.1 Hypothermia affects red blood cell rheology and increases serum viscosity (30), factors that may contribute to optic nerve ischemia. Finally, Dunker et al. reported anemia and facial swelling as risk factors for developing PION from hypotension in postoperative patients (31). Anemia is known to be an etio-logic factor of ION by reducing the oxygen delivery to the optic nerve (32). Such risk factors are commonly present in patients with severe trauma who are in shock, receive massive fluid resuscitation, develop SIRS and anasarca. All of these factors were present in our patient.

The typical presentation of PION consists of acute visual loss, afferent pupillary defect, and the absence of ocular pain or headache. The majority of patients with PION have immediate onset of visual loss, although a minority can have their presentation delayed from several hours to 10 days (17-19). This delay may be due to swelling of the isch-emic neurons within the confines of the scleral canal. This swelling eventually impinges on the vascular supply and converts a reversible ischemic insult into irreversible axonal necrosis (33). The severity of visual deficit is bilateral, and can range from small field defects and diminished acuity to complete loss of light perception, whereas in AION loss of vision is almost always unilateral (4). The afferent pupillary response corresponds to the degree of visual loss, with loss of pupillary response in severe injuries, as in our patient.

Ophthalmoscopic examination in PION does not reveal any initial changes, but mild disk edema can be seen within a



few days. Over a period of 2 to 3 weeks, the swelling dis-sipates and is replaced by an atrophic optic disk (34). In contrast, AION, generally demonstrates sectoral optic nerve edema, and manifests peripapillary hemorrhages with the edema (4). Also, computed tomography of the orbit may show enlargement of the intraorbital portion of the optic nerve (33). Furthermore, fluorescent angiography reveals a delay in the onset of perfusion of the choroidal circulation in comparison with the retinal circulation (35).

ION is a diagnosis of exclusion. Causes such as inflamma-tion, extrinsic compression, or demyelinating disease need to be excluded. In particular, vascular causes of loss of vision need to be excluded in patients with extensive trauma. Retinal artery occlusion due to emboli usually resolves within a few hours, but may persist. Hypotensive retinopathy or venous stasis retinopathy, involves poor arterial perfusion pressure with chronic tissue ischemia, often from carotid occlusive disease (36). Cortical blindness also must be excluded, since hypotension may cause infarction or embolism of watershed areas in parietal or occipital lobes. Cortical blindness can be differentiated from PION by a normal pupillary response to light and normal ophthalmoscopic findings. CT or MRI of the brain can also make this distinction (37).

Suspicion of ION in a trauma patient must prompt an urgent multidisciplinary approach, including ophthalmologic con-sultation. The treatment of PION remains unclear. Connolly et al. reported three patients whose vision improved due to early diagnosis and treatment by reversing the systemic hypotension and increasing the level of the hematocrit (38). Systemic high-dose steroid therapy initiated within the first 48 hours, has been used successfully in the management of nontrauma patients (35). However, other authors report no salvage of vision after steroid therapy (17-19). Wilson et al. state the importance of lowering the intraocular pressure by using mannitol, acetazolamide, and topical timolol, in addition to the correction of hypotension and anemia (39). Vasoconstrictors should be used sparingly, because they may decrease perfusion to the optic nerve (2). The benefit of these therapeutic measures is not well known since they have not been evaluated in trauma patients with ION. We believe that unlike abdominal and peripheral compartment syndromes, ocular compartment syndrome is not easily accessible for decompression at time of presentation, making ION a disease with poor prognosis.

The trauma and critical care team should be aware of the possibility of visual loss in patients with shock, massive fluid resuscitation, abdominal compartment syndrome, and concomitant SIRS. The incidence of ION could increase with time since improvement in trauma care is allowing

trauma patients with shock and massive fluid resuscita-tion to survive injuries that were heretofore fatal. Avoiding hypotension and anemia may be likely preventable mea-sures. Nevertheless, measures for prevention of PION will be limited in patients requiring massive fluid resuscitation for survival in the first 24 hours of injury. We propose that measurements of intraocular pressure during the resuscita-tion phase should be evaluated in trauma patients since it could be an indicator of decreased blood flow to the optic nerve. Treatments focusing on increasing oxygen delivery to the optic nerve and at the same time decreasing elevated intraocular pressure should be assessed in trauma patients. REFERENCES

1. Cullinane DC, Jenkins JM, Reddy S, et al. Anterior ischemic optic neuropathy: a complication after systemic inflamma-tory response syndrome. J Trauma. 2000;48:381-386.

2. Williams EL. Postoperative blindness. Anesthesiol Clin North America. 2002;20:605-622.

3. Shaked G, Gavriel A, Roy-Shapira A. Anterior ischemic optic neuropathy after hemorrhagic shock. J Trauma. 1998;44:923-925.

4. Pincus F. Uber sehstorungen nach blutverlust. Arch Clin Exp Ophthalmol. 1919;98:152–155.

5. Locket S. Blindness associated with hemorrhage. Br J Ophthalmol. 1949;33:543–545.

6. Hoyt WF, Walsh FB. Cortical blindness with partial recovery following acute cerebral anoxia from cardiac arrest. Arch Ophthalmol. 1958;60:1061-1069.

7. Romanul FCA, Abramowicz A. Changes in brain and pial vessels in arterial border zones: a study of 13 cases. Arch Neurol. 1964;11:40-65.

8. Williams EL, Hart WM, Tempelhoff R. Postoperative isch-emic optic neuropathy. Anesth Analg. 1995;80:1018-1029.

9. Hollenborst RW, Wagener HP. Loss of vision after distant hemorrhage. Prog Med Sci. 1950;219:209.

10. Dranie SM, Morgan RW, Sweeney WP. Shock induced optic neuropathy. N Engl J Med. 1973;288:392.

11. Johnson MV, Kincaid MC, Trobe JD. Bilateral retrobulbar optic nerve infarctions after blood loss and hypoten-sion: a clinicopathological case study. Ophthalmology. 1987;94:1577-1584.

12. Goodwin JA. Acute ischemic optic neuropathy. JAMA. 1985;254:951-952.

13. Bouzaienne M, Deboise A, Kheyar A. Cecite bilaterale irreversible apres curage cervical fonctional bilateral: a propos d’un cas et revue de la literature. Rev Stomatol Chir Maxillofac. 1994;95:226-232.

Systemic inflammatory response syndrome and posterior ischemic optic neuropathy after blunt trauma

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14. Vallejo A, Lorente JA, Bas ML, Gonzalez Y. Blindness due to anterior ischemic optic neuropathy in a burn patient. J Trauma. 2002;53:139-141.

15. Asensio JA, Forno W, Roldan GA, Gambaro E, Petrone P. Posterior ischemic optic neuropathy related to profound shock after penetrating thoracoabdominal trauma. South Med J. 2002;95:1053-1057.

16. Hayreh SS: Posterior ischemic optic neuropathy. Ophthalmologica. 1981;182:29-41.

17. Isayama Y, Takashi T, Inove M. Posterior ischemic optic neuropathy. Ophthalmologica. 1983;187:141-147.

18. Isayama Y, Takashi T. Posterior ischemic optic neuropathy. histopathology of the idiopathic form. Ophthalmologica. 1983;187:8-18.

19. Shimo-Oku M, Miyakazi S. Acute anterior and posterior isch-emic optic neuropathy. Jpn J Ophthalmol. 1984;28:159-170.

20. Quigley HA, Miller NR, Green WR. The pattern of optic nerve fiber loss in anterior optic neuropathy. Am J Ophthalmol. 1985;100:769-776.

21. Perkins SA, Margarall LE, Maizel LA. Resolved incomplete central artery obstruction simulating ischemic optic neu-ropathy. Ann Ophthalmol. 1988;20:61-67.

22. Hayreh SS. Anterior ischemic optic neuropathy. Arch Ophthalmol. 1981;99:1030-1040.

23. Hayreh SS. Anterior ischemic optic neuropathy. Terminology and pathogenesis. Br J Ophthalmol. 1974;58:955-963.

24. Boghen DR, Glaser JS. Ischemic optic neuropathy: the clinical profile and history. Brain. 1975;98:689-708.

25. Doro S, Lessel S. Cup-disk ratio and ischemic optic neu-ropathy. Arch Ophthalmol. 1985;103:1143-1144.

26. Haciyakupoglu G, Isiguzel I, Zorludemir S, et al. Early ultrastructural findings and superoxide dismutase levels in experimental ischemic optic neuropathy-effect of hyperten-sion and hypotension. Ophthalmologica. 2001;215:55-60.

27. Marks SC, Jaques DA, Hirata RM, Saunders JR Jr. Blindness following bilateral radical neck dissection. Head Neck. 1990;12:342-345.

28. Ellemberger, C. Ischemic optic neuropathy as a possible early complication of vascular hypertension. Am J Ophthalmol. 1979;88:1405.

29. Bloomfield GL, Ridings PC, Blocher CR, Maramou A, Sugerman HJ. Effects of increased intra-abdominal pres-sure upon intracranial and cerebral perfusion pressure after volume expansion. J Trauma. 1996;40:936–943.

30. Chihara H, Blood AB, Hunter CJ, Power GG. Effect of mild hypothermia and hypoxia on blood flow and oxygen consumption of the fetal sheep brain. Pediatric Research. 2003;54:665-671.

31. Dunker S, Hsu HY, Sebag J, Sadun AA. Perioperative risk factors for posterior ischemic optic neuropathy. J Am Coll Surg. 2002;194:705-710.

32. Brown RH, Schauble JF, Miller NR. Anemia and hypotension as contributors to perioperative loss of vision. Anesthesiology. 1994;80:222–226.

33. Wemsterm IM, Duckrow RB, Beard D. Regional optic nerve flow and its regulation. Invest Ophthalmol Vis Sci. 1983;24:1559-1565.

34. Bill A. Blood circulation and fluid dynamics in the eye. Physiol Rev. 1975;22:384-317.

35. Lee AG. Reversible loss of vision due to posterior ischemic optic neuropathy. Can J Ophthalmol. 1995;30:327-329.

36. Dugan JD, Gree WR. Ophthalmologic manifestations of carotid occlusive disease. Eye. 1991;5:226-238.

37. Alfano JE, Fabritius RE, Garland MA. Visual loss following mitral commissurotomy for mitral stenosis. Am J Ophthalmol. 1957;44:213-216.

38. Connolly SE, Gordon KB, Horton JC. Salvage of vision after hypotension-induced ischemic optic neuropathy. Am J Ophthalmol. 1994;117:235-242.

39. Wilson JF, Freeman SB, Breene DP. Anterior ischemic optic neuropathy causing blindness in the head and neck surgery patient. Arch Otolaryngol Head Neck Surg. 1991;117:1304-1306.

46

MANAGEMENT OF RENAL TRAUMA

Eddy H. Carrillo, MD

Memorial Regional HospitalHollywood, Florida


Injuries to the kidney occasionally represent a diagnostic and therapeutic problem for the trauma surgeon. Many are minor injuries that escape diagnosis; some are very simply managed; a few constitute ultimate challenges to surgical judgement and surgical skills. Appropriate balances between informed conservatism and definitive surgical treatment is regularly required. Renal related mortality is very low, and usually is the result of associated injuries, usually to major abdominal vascular structures, liver, pancreas, or central nervous system (1).

Currently, most institutions classify renal injuries fol-lowing the definitions put forth by the Organ Injury Scaling Committee (OIS) of the American Association for the Surgery of Trauma (Table 1) (2). Since the manage-ment of blunt and penetrating renal injuries is somehow different, it is important to separate both conditions for a better understanding.

and contact trauma from athletic activities or assaults. Approximately one half of patients with blunt renal injuries will have other associated injuries. In general, blunt renal injuries can be classified as follows:

Contusions and Minor Lacerations: These types of injuries account for 80%-85% of all renal injuries. There is hem-orrhage in the renal parenchyma, but the capsule remains intact. Minor cortical lacerations can be present. Hematuria and occasionally flank pain are usually associated with this type of injuries.

Major Lacerations: Only 10% of renal trauma consists of deep lacerations, with extravasation of urine due to involve-ment of the collecting system.

Pedicle Injuries: Renal pedicle injuries are usually asso-ciated with severe renal lacerations. Occasionally there is involvement of the renal artery or vein. Accidents in which there is sudden deceleration can cause intimal tears of renal artery, producing thrombosis and ischemia.

Diagnosis

Gross hematuria is usually seen in patients with significant renal injuries. However, up to 25% o patients can present without gross hematuria. Microsocopic hematuria is contro-versial as a sentinel for significant renal injuries. However, in our unit, we believe that any patient with > 25 red blood cells/hpf in a urinary analysis deserve diagnostic work-up.

Currently, the diagnostic test of choice is an enhanced abdominal computed tomography (CT) scan. The greatest advantage of CT scan compared to intravenous pyelography (IVP) is its ability to better delineate the renal parenchyma as well as to reveal the integrity of the collecting system. Based upon the findings of a well-done CT scan, most deci-sion can be made in a very expeditious manner.

Probably the most controversial area in blunt renal injuries is the subject of acute thrombosis of the renal artery following

Grade I Contusions and subcapsular hematomas

Grade II Cortical lacerations. Non-expandable peri-nephric hematoma

Grade III Deep parenchymal lacerations with medular extension. Segmental infarcts

Grade IV Lesions to the renal hilum with active bleeding. Involvement of the collecting system or seg-mental devascularization

Grade V Shattering of the kidney. Avulsion of the renal ves-sels at the hilum. Thrombosis of the renal artery

Table 1. Classification of Renal Injuries

BLUNT RENAL INJURIES

The most common cause of renal injuries is blunt trauma from motor vehicle crashes (MVC), falls from heights,

Management of renal trauma

47

blunt abdominal injuries. These injuries usually occur 2 cm from the origin of the renal artery, most commonly the left side. It has been suggested that the right kidney is better fixed in position by the overlying liver, duodenum and vena cava, and therefore, less susceptible to rapid deceleration than the left kidney, which may be more mobile. In addition, the right renal artery, which is longer than the one in the left side, may be able to distribute stretching along its length owing to deceleration (3, 4). The diagnosis is difficult, and is usually made with an abdominal CT scan. Selective renal arteriography is the most sensitive test, but routine use of angiography is not indicated if the abdominal CT scan documents absence of renal enhancement and excretion and the presence of a cortical rim sign (5).

Treatment

Most renal lesions resulting from blunt abdominal injuries can be managed non-operatively. However, up to 10% of patients will eventually need an operation due to associ-ated vascular injuries, deep lacerations associated with urinary extravasation, or persistent hemorrhage from the renal parenchyma. Surgery usually is indicated for ongoing hemorrhage or urinary extravasation to minimize the risks of infection and delayed loss of the kidney.

Management of blunt renal artery injuries has remained very controversial, because the most critical factor in pre-serving renal function is to reestablish blood flow in less than 6 to 12 hours; otherwise, the renal loss rate is 50% and one-third of the patients will require delayed nephrectomy after the initial repair. Repair is usually undertaken with an interposition vein graft. We caution against early nephrec-tomy because there is evidence of delayed reconstitution, either spontaneously or after failed surgical reconstruction (6). Delayed hypertension can be seen in up to two-thirds of these patients and may require delayed nephrectomy (7).

PENETRATING RENAL INJURIES

Penetrating renal injuries are less common than blunt inju-ries. Because of the proximity of major vascular structures, mortality due to associated injuries is common.

Treatment

The usual surgical indications are ongoing hemorrhage from lesion to the renal hilum, deep lacerations with persistent and severe hematuria or urine extravasation. In general, the goal of surgery in these patients is to control hemorrhage, minimize urinary contamination and preserve renal func-tion. There is a close relationship between nephrectomies and delayed in surgical intervention, therefore, surgical intervention if indicated, should never be delayed.

Initial vascular control of the renal vessels is very contro-versial. If preliminary vascular control is achieved before opening Gerota’s fascia and entering the hematoma, the left renal vein is isolated and retracted up or down, depending on the origin of the renal arteries. For patients with large peri-renal hematomas dissecting toward the midline, it is difficult to identify the renal pedicle near the aorta without a signifi-cant blood loss. The is data that shows that the performance of nephrectomy was influenced by the severity of the renal injury and not by obtaining preliminary vascular control (8).

REFERENCES

1. Carrillo EH, Bergamini TB, Miller FB, Richardson JD. Abdominal vascular injuries. J trauma. 1997; 43:164.

2. Moore EE, Shackford SR, Pachter HL, et al. Organ injury scaling: spleen, liver, and kidney. J Trauma. 1989; 29:1664.

3. Barlow B, Gandi R. Renal artery thrombosis following blunt trauma. J Trauma. 1980; 20: 614.

4. Carrol PR, McAninch JW, Klosterman P, et al. Renovascular trauma: risk assessment, surgical management, and outcome. J Trauma. 1990; 30:547.

5. Sclafani SJ. The diagnosis of bilateral renal artery injury by computed tomography. J Trauma. 1986; 26:295.

6. Greenholz SK, Moore EE, Peterson NE, et al. Traumatic bilateral renal artery occlusion: successful outcome without surgical intervention. J Trauma. 1986; 26:941.

7. Dinchman KH, Spirnak JP. Traumatic renal artery throm-bosis: evaluation and treatment. Semin Urol. 1995; 13:90.

8. Atala a, Miller FB, Richardson JD, et al. Preliminary vascular control for renal trauma. Surg Gynecol Obstet. 1991; 172:386.

48

THE MODERN APPROACH TO PENETRATINGNECK TRAUMA

Stephen C. Gale, MD; Vicente H. Gracias, MD, FACS1

1 Assistant Professor of Surgery, Department of Surgery Division of Traumatology and Surgical Critical Care University of Pennsylvania School of Medicine


INTRODUCTION

The neck is a highly complex anatomic region with critical aerodigestive, vascular, and neurologic structures concen-trated in a very small area and volume. The evaluation and management of penetrating injury to this region is chal-lenging to trauma surgeons and continues to evolve. The key to evaluating any gunshot or stab victim is reliably tracking the tissues penetrated by the missile or blade. The inability to determine “trajectory” by examination alone leads to clinical uncertainty and is the crux of controversies surrounding the evaluation and treatment of patients with these complex wounds. Because missed injuries or delays in diagnosis lead to increased morbidity and mortality with penetrating neck trauma (1), surgeons do agree on the importance of rapid and confident injury identification and exclusion of life threatening cervical injuries.

INITIAL ASSESSMENT

The initial evaluation of patients with penetrating neck trauma is largely dependent on the physical examination and physiologic status of the patient. Hemodynamic instability or hard signs of injury to vital structures mandate immediate operative exploration and repair. Signs of vascular injury include pulsatile bleeding, expanding hematoma, bruit, or unilateral upper extremity pulse deficit. Aerodigestive injury is suggested by subcutaneous emphysema, wound bubbling, hoarseness, stridor, or airway compromise. Secondary testing early in the evaluation of these patients is limited and usually mandates urgent operative exploration and stabilization.

HEMODYNAMICALLY NORMAL PATIENTS

Classical Approach

The traditional approach to managing hemodynamically normal patients with penetrating anterior neck trauma uti-

lizes the classical neck “zones” as described by Roon and Christensen in 1979 (2). Based largely on the experience of Fogelman and Stewart in 1956 (3), sub-platysmal penetra-tions to Zone II (between the cricoid and the angle of the mandible) have classically mandated complete operative exploration to evaluate the vasculature, trachea, and esoph-agus in all patients. With Zone I injuries (below the cricoid) and Zone III injuries (above the angle of the mandible), due to the complexity of operative exposure, traditional evalua-tion relies upon angiography to interrogate the vasculature as well as endoscopy and contrast radiography to evaluate the aerodigestive tract.

Selective Approach

While there has been little controversy surrounding the management of Zone I or Zone III injuries, which are not amenable to accurate physical examination, the manage-ment of Zone II penetrations has continued to evolve. In 1994, Atteberry (4) and others described 53 patients with penetrating injury to Zone II. Of these patients, 19 under-went immediate operation based on physical signs. The remaining 34 were managed selectively based on physical exam: 6 patients had angiograms, 18 had carotid duplex, and the others were observed. There were no missed vascular injuries. This report was followed in 1997 by Demetriades (5) and others who prospectively evaluated 223 patients with penetrating neck trauma and included injury to any zone. They compared physical examination findings with the results of angiography, duplex exam, and esophagram and concluded that physical examination could be used to triage patients for further vascular or esophageal studies. They also noted that duplex was a reliable alternative to angiography. In 2003, Azuaje (6) and others reinforced the sensitivity of physical exam to identify vascular injuries requiring repair. They retrospectively reviewed 152 stable patients underwent four-vessel angiogram after penetrating neck injury. Of the 89 patients who had no physical examination findings suggesting vascular injury, only 3 had positive angiograms none of whom required operative

The modern approach to penetrating neck trauma

49

intervention. They reported a sensitivity of 93% and nega-tive predictive value of 97% of physical exam to identify and exclude vascular injury after penetrating neck trauma and recommended a selective approach based on physical examination findings. While certainly well-described iso-lated physical exam has not received wide acceptance and a more commonly accepted “selective management” strategy has emerged. This approach involves the employing on secondary diagnostic testing for all 3 cervical zones based on penetration of the platysma, normal hemodynamics, and the absence of “hard” signs of injury. In this scheme, all patients who do not require immediate operation undergo vascular and aerodigestive interrogation with angiography, bronchoscopy, and esophagoscopy and/or esophagography to exclude injury (7-12). Operative strategies are then directed at specific identified injuries.

This non-specific algorithm is certainly accurate and reli-able to identify and exclude injury. However, this approach does have disadvantages. First, this strategy is labor and resource intensive often requiring input from multiple spe-cialties. And, as many authors have indicated, the overall diagnostic yield is low with only 10% of patients who undergo selective management having findings on angiog-raphy or endoscopy that will require operative intervention (5). Next, this approach is expensive with costs in excess of $2000 per patient (5). Finally, these diagnostic procedures are invasive and carry a small but real risk of complications (13). Interestingly, Meyer (14) and others prospectively evaluated the “selective approach” versus mandatory exploration. In 113 stable patients with Zone II penetrations arteriography, panendoscopy, and esophagography were performed in all patients followed by mandatory explora-tion. They identified 6 major vascular or visceral injuries that were missed using the selective approach.

In the search for less invasive diagnostic techniques, Montalvo et al. (15) and Demetriades et al. (5) found color duplex ultrasonography to be an accurate alternative to angiogram for arterial evaluation in Zone II or Zone III pen-etrations. However, this modality is of limited availability, is operator dependent, and requires specialist expertise for interpretation. Ultrasound is further inhibited by patient body habitus, its inability to image the skull base, and does not offer aerodigestive tract evaluation.

Modern Approach

With these different issues above in mind, surgeons continue to question whether rigid algorithmic protocols involving multiple invasive studies should apply to the evaluation of all stable patients who sustain penetrating neck injuries.

Coupled with the increasing incidence of multi-zone pen-etrations, the profession-wide trend toward less invasive diagnostic approaches, and the ever-increasing speed and improving resolution of multi-detector computed tomog-raphy (CT) scanners, newer algorithms are beginning to CTcscan in their diagnostic approach.

In addition to being entirely non-invasive, helical/multide-tector CT with timed contrast injection has the advantage of providing information on all vital neck structures. Not only are the arterial and aerodigestive structures imaged, but major venous, nervous, and bony injuries can also be assessed as well. Trajectory is often demonstrated by this modality with one caveat: most clearly with ballistic trauma not stabs. When helical CT clearly visualizes trajectory and excludes important structures from the path of injury no further imaging is needed. In patients where the wounding trajectory is in proximity to a vital structure or where tra-jectory is unclear, helical CT serves as a triage tool to select those structures that require further individualized invasive diagnostic evaluation.

There is a growing body of literature to support the use CT neck/ angiography to evaluate patients after penetrating neck trauma. Ofer (16) studied 16 patients with potential carotid artery injuries and determined that CT angiography is highly accurate in diagnosing vascular injury and allowing successful non-operative management in patients with neg-ative CT scans. In 2001, Gracias et al. (18) reported a series of 23 patients and found that CT was a safe and effective modality to “to direct or eliminate further invasive studies in selected stable patients with penetrating neck injury.” In this study CT scan was shown to effectively reduce the resources needed to evaluate multi-zone gun shots to the neck and which patients could be safely observed without further evaluation. CT scan signs including skin violation, subcutaneous fat stranding, soft tissue air or hematoma, vertebral fracture, etravasation of contrast and missile loca-tion were used to determine trajectory. Multi-zone trajec-tory was identified in 43% of patients. Mazolewski (17) prospectively compared trauma-surgeon evaluated neck CT with mandatory operative exploration after zone II penetra-tion and found a sensitivity of 100% for identifying injuries that would require operative intervention. In 2002, a pro-spective study by Munera (19) evaluated 175 patients with penetrating neck injury by CT angiography. They were able to accurately characterize vascular injuries in 27 (15.6%) patients and direct them to appropriate therapy. The other 146 patients were successfully observed without further intervention and without missed injury. In 2003 Gonzalez (20) prospectively evaluated helical CT scan with oral but no IV contrast versus oral contrast esophagography to detect



esophageal injuries in stable patients after penetrating neck trauma. The study reported equivalent accuracy of these modalities in the evaluation of penetrating injury to the cer-vical esophagus and noted that the sensitivity of helical CT was similar to physical examination. Of note, 86% of the patients were stab victims. Certainly one of the recognized limitations of the use of CT in penetrating neck trauma is its difficulty in detecting trajectory of knife penetrations. In particular, small pharyngoesophageal knife injuries will be difficult to detect with CT scan.

Based on the current evidence there is a role for the use of helical CT in evaluating stable patients with penetrating trauma to the neck who do not have hard signs of vascular or aerodigestive injury. Irrespective of the zone of penetration, the use of this technology is an acceptable method to deter-mine trajectory and thereby triage patients to the operating room, to further specific invasive studies, or to observation and serial examination. If helical CT is not immediately available, if the findings on helical CT are inconclusive, or if the findings do not match the clinical picture, traditional methods of evaluating penetrating neck trauma with angiog-raphy, panendoscopy, esophagography, or operative explora-tion should be pursued. As helical CT technology continues to improve and as surgeons become more comfortable with its use, the role of CT in evaluating stable patients with pen-etrating injuries will continue to expand.

REFERENCES

1. Shama DM, Odell J. Penetrating neck trauma with tracheal and oesophageal injuries. British Journal of Surgery 1984. 71(1):534-6.

2. Roon AJ, Christensen N. Evaluation and treatment of pen-etrating cervical injuries. J Trauma. 1979;19(6):391-7.

3. Fogleman MJ, Stewart RD. Penetrating wounds of the neck. Am J Surg. 1956; 91:581-596.

4. Atteberry LR, Dennis JW, Menawat SS, Frykberg ER. Physical examination alone is safe and accurate for evalua-tion of vascular injuries in penetrating zone II neck trauma. J Am Col Surg.1994; 179:657-662.

5. Demetriades D, Theodorou D, Cornwell E, Berne TV, Asensio J, Belzberg H, Velmahos G, Weaver F, Yellin A. Evaluation of penetrating injuries of the neck: Prospective study of 223 patients. World J Surgery.1997; 21:41-48.

6. Azuaje RE, Jacobson LE, Glover J, et al. Reliability of physical examination as a predictor of vascular injury after penetrating neck trauma. Am Surg 2003; 69(9):804-7.

7. Back MR, Baumgartner FJ, Klein SR. Detection and evaluation of aerodigestive tract injuries caused by cervical and transmedi-astinal gunshot wounds. J Trauma. 1997;42(4):680-686.

8. Biffl WL, Moore EE, Rehse DH, Offner PJ, Francoise RJ, Burch JM. Selective management of penetrating neck trauma based on cervical level of injury. Am J Surg 1997; 174(6):678-82.

9. Klyachkin ML, Rohmiller M, Charash WE, Sloan DA, Kearney PA. Penetrating injuries of the neck: selective man-agement evolving. Am Surg 1997; 63(2):189-94.

10. Van As AB, van Deurzen DF, Verleisdonk EJ. Gunshots to the neck: selective angiography as part of conservative man-agement. Injury 2002; 33(5):453-6.

11. Noyes LD, McSwain NE, Markowitz IP. Panendoscopy with Arteriography versus mandatory exploration of penetrating wounds to the neck. Ann Surg 1986; 204(1):21-31.

12. Asensio JA, Valenziano CP, Falcone RE, Grosh JD. Management of penetrating neck injuries. The contro-versy surronunding Zone II injuries. Surg Clin North Am. 1991;71(2):267-298.

13. Eddy VA. Is routine Arteriography mandatory for penetrating injury to zone 1 of the neck? Zone 1 Penetrating Neck Injury Study Group. J Trauma. 2000; 48(2):208-214.

14. Meyer JP, Barrett JA, Schuler JJ, Flanigan DP. Mandatory vs. selective exploration for penetrating neck trauma. A prospec-tive assessment. Arch Surg 1987; 122(5):592-7.

15. Montalvo BM, LeBlang SD, Nunez DB, Ginzberg E, Klose KJ, Becerra JL, Kochan JP. Color Doppler sonography in penetrating injuries to the neck. Am J Neurorad. 1996;17(5):943-51.

16. Ofer A, Nitecki SS, Braun J, et al. CT angiography of the carotid arteries in trauma to the neck. Eur J Vasc Endovasc Surg 2001; 21(5):401-7.

17. Mazolewski PJ, Curry JD, Browder T, Fildes J. Computed tomographic scan can be used for surgical decision making in zone II penetrating neck injuries. J Trauma 2001; 51:315-319.

18. Gracias VH, Reilly PM, Philpott J, Klein WP, Singer M, Schwab CW. Computed tomography in the evaluation of penetrating neck trauma: a preliminary study. Arch Surg 2001; 136:1231-1235.

19. Munera F, Soto JA, Palacio D, et al. Penetrating Neck Injuries: helical CT angiography for initial evaluation. Radiology 2002; 370:366-372.

20. Gonzalez RP, Falimirski M, Holevar MR, Turk B. Penetrating zone II neck injury: Does dynamic computed tomographic scan contribute to the diagnostic sensitivity of physical examination for surgically significant injury? A prospective blinded study. J Trauma 2003; 54:61-65

51

OPTIMIZING TRAUMA CARE IN SPECIAL POPULATIONS: PREGNANT PATIENT

Grace S. Rozycki, MD, RDMS, FACS

Professor of SurgeryDirector, Trauma/Surgical Critical CareEmory University School of MedicineGrady Memorial Hospital, Atlanta, Georgia


INTRODUCTION

Although maternal mortality rates in the United States have declined markedly the number of deaths due to injury during pregnancy continues to increase, especially as victims of vio-lent crime. In one multicenter review, penetrating trauma and assaults were responsible for 20% of the injuries resulting in admission of pregnant patients to trauma centers.

It is therefore essential that all trauma surgeons, emergency physicians, and obstetricians understand the anatomic and physiologic characteristics unique to pregnancy and prin-ciples of resuscitation and treatment following trauma in order to guarantee the best possible outcome for both the injured mother and her fetus.

ANATOMIC AND PHYSIOLOGIC CHANGES UNIQUE TO PREGNANCY

Although the initial assessment and management priori-ties for resuscitation of the injured pregnant patient are the same as those for other traumatized patients, the specific anatomic and physiologic changes that occur during preg-nancy may alter injury response and hence necessitate a modified approach to the resuscitation process.

Cardiovascular System

At 10 weeks gestation plasma and blood volume begin to expand because of increases in estrogen, progesterone, plasma renin, and aldosterone. Additionally, tubular sodium resorption is increased and 6 to 8 L total body water is retained. This hypervolemic state is protective for the mother because fewer red blood cells are lost during hemorrhage and hence, oxygen-carrying capacity is minimally affected.

However, this pregnancy-induced hypervolemia may create a false sense of security for the resuscitating physician because almost 35% of maternal blood volume may be lost prior to manifestation of signs of maternal shock.

This 30%-40% increase in plasma volume is accompanied by an erythroid hyperplasia in the bone marrow, resulting in a 15% increase in red blood cell mass and a “physiologic anemia.” A hemoglobin level < 11 g/dL is considered abnormal. During the first trimester, the maternal pulse rate increases by about 10 to 15 beats per minute and remains that way until delivery. As the diaphragm becomes progres-sively more elevated secondary to the enlarging uterus, the heart is displaced to the left and upward, resulting in a lateral displacement of the cardiac apex. Often there is a benign pericardial effusion which will be seen as a positive finding on the FAST emanation and as an enlarged cardiac silhouette chest x-ray.

Maternal blood pressure decreases during the first trimester, reaches its lowest level in the second trimester, and then rises toward pre-pregnancy level during the final two months of gestation. Mean values for the first-trimester: 105/60 mmHg; second trimester: 102/55 mmHg; and third trimester: 108/67 mmHg are important to note because significant elevations may indicate pregnancy-induced hypertension.

Hemodynamics

By the end of the first trimester, cardiac output increases by 25% and near term a cardiac output of about 6.2 + 1 L/min is common. In the healthy gravida, this increased workload on the heart is well tolerated.

However, when the patient is in the supine position and the inferior vena cava is partially obstructed by the gravid uterus, there is a decrease in venous blood return to the heart, resulting in a lower cardiac output, causing the supine hypotensive syndrome. Turning the mother onto her left side restores the circulation and increases cardiac output. A point worth emphasizing is that, in the supine position,



the enlarged uterus also compresses the aorta, reducing the pressure in the uterine arteries and compromising some blood flow to the fetus.

During labor and delivery, maternal hemodynamics are fur-ther altered. For example, with each uterine contraction, 300 mL to 500 mL blood is expelled from the uterus, increasing systemic blood volume and raising central venous pres-sure. Immediately after delivery, there is a dramatic rise in cardiac output because the contracted uterus shunts about 1000 mL blood into the systemic circulation and increases venous return to the heart.

Respiratory System

Several changes in the maternal respiratory system occur during pregnancy to meet increased oxygen requirements. As the uterus enlarges, the diaphragm rises about 4 cm and the diameter of the chest enlarges by 2 cm, thereby increasing the substernal angle. These changes occur very early in pregnancy secondary to hormonal effects, and then later from mechanical pressure caused by the enlarged uterus. Care should be taken to consider these anatomic changes when thoracic procedures such as tube thoracosto-mies or thoracenteses are being performed. The most notable changes in pulmonary volumes and capacities are the pro-gressive increases in tidal volume and minute ventilation The functional residual capacity (FRC) decreases because of a decline in expiratory reserve and residual volumes. The net result is an unchanged arterial partial pressure of oxygen (PaO2), a reduction in the partial pressure of carbon dioxide (PcO2) to 30 torr, and a slight compensatory decrease in plasma bicarbonate levels. Therefore, pregnancy is a state of partially compensated respiratory alkalosis. Relative to these changes, the injured gravida tolerates apnea poorly because of the reduced FRC. Hence, supplemental oxygen is always indicated for these patients.

Gastrointestinal System

Increased levels of progesterone and estrogen inhibit gastrointestinal motility, intestinal secretion, and nutrient absorption. Additionally, the angle of the gastroesophageal junction is altered such that the lower esophageal sphincter is displaced into the thorax. This alteration, along with hormonal changes, decreases gastroesophageal sphincter competency, which increases the potential for aspiration. The hormone, gastrin, produced by the placenta, raises the acid, chloride, and enzyme contents of the stomach during pregnancy. Studies have demonstrated that parturients who have an elective cesarean section after an overnight fast have >25 mL acidic (pH <2.5) gastric contents at the time

of surgery. Therefore, a nasogastric tube should be inserted to decompress the stomach and prevent aspiration.

Renal System

To accommodate both maternal and fetal metabolic and cir-culatory requirements, renal blood flow increases between 25% and 50% during gestation. Consequently, blood urea nitrogen (BUN) and serum creatinine are reduced. However, as pregnancy progresses, the ureters and bladder are compressed by the uterus, resulting in hydronephrosis and hydroureter.

The growth hormone effect of placental lactogen, increase in blood volume, and rise in cardiac output accommodate the increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). The increase in GFR is greater than that of the RPF (95% vs. 50%). Therefore, more plasma is filtered, reducing the serum protein concentration and hence the plasma oncotic pressure.

Musculoskeletal System

The softening and relaxation of the interosseus ligaments during pregnancy cause increased mobility of the sacroiliac and sacrococcygeal joints, and widening of the symphysis pubis. These changes, coupled with an enlarged uterus, disrupt the maternal center of gravity, for which the mother compensates by assuming a lordotic posture. This resultant change in gait stability places the gravida at increased risk for trauma, especially falls.

INITIAL ASSESSMENT AND MANAGEMENT

When faced with a seriously injured pregnant patient and the associated confusing maternal and fetal needs, the clinician must clearly identify priorities. Armed with the knowledge of anatomic and physiologic changes that occur during pregnancy, the clinician is better prepared to manage the resuscitation and associated subtleties that may alter the patterns, severity, and manifestations of injury. The resuscitation and stabilization should, therefore, be modi-fied to accommodate these changes, however the treatment priorities for an injured pregnant patient remain the same as those for the non-pregnant patient.

Primary Survey

As with any other injured patient, the primary survey addresses airway, breathing, and circulation (volume replacement/hemorrhage control), with the mother receiving treatment priority. Ensuring an adequate maternal airway

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with supplemental oxygen is essential to prevent maternal and fetal hypoxia. Severe trauma stimulates the release of maternal catecholamines which causes uteroplacental vaso-constriction, and hence compromise of fetal circulation. Because the oxyhemoglobin dissociation curve for fetal blood is different from maternal blood, small increments in maternal oxygen concentration improve oxygen content and reserve for the fetus even though the maternal arterial oxygen content does not change appreciably.

In the supine position, the gravida may become hypoten-sive due to the mechanical effects of the enlarged uterus causing aortocaval compression. Prevention of the supine hypotensive syndrome is accomplished by placing the patient in the left lateral decubitus position or in the right hip-flexed position. Patients with suspected spinal injury can be secured on a backboard and then tilted to the left. As a final measure, however, the uterus can be manually displaced to the left side.

Hypovolemia should be suspected long before it becomes apparent. Because of the physiologic hypervolemia associ-ated with pregnancy, signs of shock may be delayed. Hence, vigorous crystalloid resuscitation is encouraged even for patients who appear normotensive.

The pneumatic anti-shock garment (PASG) may be used to stabilize fractures or control hemorrhage. In the pregnant patient, inflation of the abdominal compartment is contra-indicated because of the increased pressure transmitted to the fetus and the further compromise of venous return.

Secondary Survey

History and Physical ExaminationFollowing the primary survey and performance of life-saving measures, the secondary survey is initiated. This consists of obtaining a thorough history, including obstetric history; performing a physical examination; and evaluating and monitoring the fetus.

An accurate prenatal history is crucial because co-morbid factors such as pregnancy-induced hypertension, diabetes, and congenital heart disease may alter management deci-sions. Furthermore, a history of preterm labor, placental abruption, or placenta previa place the patient at increased risk for recurrence. Obstetric history includes the date of the last menstrual period, expected date of delivery, when the first perception of fetal movement occurred, and any problems or complications of the current and previous pregnancies.

Determination of uterine size approximates gestational age and fetal maturity. Fundal height measurement is a rapid

method of estimating fetal age. For example, if the most superior part of the fundus is palpated at the umbilicus, the fetal age is estimated to be 20 weeks. Determination of fetal age and hence fetal maturity is an important factor in the decision matrix regarding early delivery. For example, a 26-week-old fetus is considered viable if given neonatal intensive care support.

Pelvic and rectal examinations should be performed, with special attention to vaginal discharge that contains amniotic fluid or blood, and to effacement, dilation, and fetal station.

Assessment of the injured pregnant patient must confirm or rule out (1) vaginal bleeding, (2) ruptured membranes (amni-otic sac), (3) a bulging perineum, (4) the presence of contrac-tions, and5 abnormal fetal heart rate and rhythm. These five conditions indicate the acute status of the pregnancy.

Vaginal bleeding prior to labor is abnormal and may indicate premature cervical dilation, early labor, placental abruption, or placenta previa (placement of the placenta over a portion of the cervical os).

If the amniotic sac has ruptured, umbilical cord prolapse can occur, resulting in compression of the umbilical vein and arteries. This can be detected visually by observing cloudy white or green fluid coming from the cervical os or perineum. The presence of amniotic fluid can be confirmed when Nitrazine paper turns blue-green to deep blue when the fluid is tested. Rupture of the amniotic sac is significant because of the potential for infection and umbilical cord prolapse, the latter being an obstetrical emergency requiring immediate cesarean section.

Bloody amniotic fluid is an indication of premature sepa-ration of the placenta (placental abruption) or placenta previa. In the presence of known or continuous meconium staining (green amniotic fluid), continuous electronic fetal monitoring is necessary.

A bulging perineum is caused by pressure from a presenting part of the fetus. If this occurs during the first trimester, spontaneous abortion may be imminent.

Assessment of the uterine contraction pattern is accom-plished by resting the hand on the fundus and determining the frequency, duration, and intensity of contractions. Contractions are usually rated as mild, moderate, or strong. Strong contractions are associated with true labor and this determination is important so that appropriate preparation can be made for delivery and resuscitation of the neonate if necessary.



The Kleihauer-Betke (K-B) test is used following maternal injury to identify the presence of fetal blood in the maternal circulation, that is, fetomaternal transfusion. Adult hemo-globin (HbA) is eluted in the presence of an acidic buffer, but fetal hemoglobin (HbF) is resistant. Fetal cells containing HbF are stained with erythrosin but maternal cells containing HbA fail to stain, and hence remain as “ghost cells” in the peripheral smear. The original K-B test required cell counts from the peripheral smears and a formula to determine the amount of fetomaternal hemorrhage. Currently, however, several commercial kits are available that expedite and simplify the process. Because the K-B test can determine the risk of isosensitization in Rh-negative gravidas, it is rec-ommended for injured Rh-negative pregnant patients in the second or third trimester to detect imminent fetal exsangui-nation. If positive, the K-B test should be repeated 24 hours later to identify ongoing fetomaternal hemorrhage. The initial dose of Rh-immune globulin is 300 micrograms, with an additional 300 micrograms administered for every 30 mL of fetomaternal transfusion estimated by the K-B test.

FETAL ASSESSMENT

Fetal evaluation begins with auscultation of heart tones and recordation of heart rate. Baseline fetal heart rate is defined as the beats/minute value that the fetal heart rate oscillates around for > 10 minutes. The normal range is 120-160 beats/min. Tachycardia is defined as a heart rate >160 and bradycardia <120 beats/min. Because fetal stroke volume is fixed, the initial response to stress such as hypotension or hypoxia is tachycardia. Auscultation for one minute will demonstrate rate and regularity, however continuous fetal monitoring best predicts fetal response to stress.

The technology of continuous electronic fetal monitoring remains the most widely used modality for fetal evaluation and is an adjunct to the monitoring of the maternal condi-tion. The use of electronic fetal heart rate monitoring per-mits the clinician to promptly identify the fetus at great risk for asphyxia and fetal death and, because it is a continuous process, allows timely provision of preventive measures.

Both external and internal techniques are used to monitor the fetal heart rate. External monitoring uses Doppler ultra-sound to detect fetal heart wall motion. Advantages of the external method include noninvasiveness and wide clinical applicability. However, motion artifact alters fetal tracing, hence information may not be as reliable. The internal or direct method involves placing an electrode directly on the presenting part of the fetus to detect the QRS pulsing con-figuration as with an echocardiogram. Because access can only be obtained if membranes have ruptured, there is an

increased chance of infection and fetal injury. This method however, provides more accurate data.

The most common cause of sudden fetal heart rate brady-cardia is acute fetal hypoxia. In the critically ill obstetric patient with hypertension, preeclampsia, or trauma, a common cause of fetal hypoxia is placental abruption. Acute fetal heart rate bradycardia may be associated with amniotic fluid embolus syndrome, acute respiratory insuf-ficiency, or eclamptic seizure. Fetal tachycardia most com-monly is related to maternal pyrexia or chorioamnionitis, however, hypoxia is also in the differential diagnosis.

A normal fetal heart rate pattern has a 95% or better cor-relation with a fetus that is well perfused. The term, “fetal distress,” indicates fetal deterioration of compensatory mechanisms, eventually resulting in malperfusion and metabolic acidosis. The usual clinical management of fetal distress is delivery by the most expeditious route.

The question often arises regarding the duration of fetal monitoring in the traumatized pregnant patient. In a pro-spective, controlled study of 85 injured patients, Pearlman and colleagues noted that 4 hours of cardiotocographic monitoring (CTM) used as a screening tool was a very sen-sitive but nonspecific indicator of adverse fetal outcome. In a review article examining several recent studies relating fetal heart rate monitoring to outcome, Kaiser found a lack of scientific evidence that CTM improved delivery out-come. The applicability of these studies to trauma patients, however, may be doubtful because the patient populations in these studies included many nontrauma patients as well.

In general, the chief concern is placental abruption, which, if severe enough, usually occurs early. Most cases of placental abruption become evident within several hours after trauma. CTM should be started in the resuscitation area to detect contractions and fetal heart rate abnormalities. A minimum of 24h CTM is recommended for patients with: frequent uterine activity (> 6 contractions per hour), abdominal or uterine tenderness, vaginal bleeding, or hypotension. After that period of time, ultrasonography is used for a fetal assessment. For patients without any of the previous signs or symptoms described, and at least 4 hours of normal CTM, discharge may be considered. However, patients should be counseled to observe for decreased fetal movements, vaginal bleeding, abdominal pain, or frequent uterine contractions.

DIAGNOSTIC MODALITIES

Following maternal stabilization/assessment and fetal evalua-tion, the extent of maternal and fetal injury is determined with

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the aid of the appropriate diagnostic modalities. Although there is much concern about radiation exposure, a diagnostic modality deemed necessary for maternal evaluation should not be withheld for fear of potential hazard to the fetus.

The Roentgen (R) is the unit of radiation exposure or inten-sity, expressed as the quantity of rays and their interaction with air. The rad is the unit of absorbed radiation and is expressed in Grays (Gy) (1 Gy = 100 rad). The rem is the unit for the amount of absorbed radiation that equals absorption of 1 R; rems are expressed as Sieverts (Sv) (1 Sv = 100 rem). The effects of radiation on the developing mammal are categorized as gross congenital malforma-tions, intrauterine growth retardation, and embryonic death. Microcephaly is the most common malformation observed in humans randomly exposed to high doses of radiation during pregnancy. This is based on the fact that the cen-tral nervous system maintains its sensitivity to radiation throughout gestation and into the neonatal period, whereas the other organ systems have much narrower periods during which obvious morphologic alterations can occur.

The critical period for injuries secondary to radiation exposure occurs during the first 8 weeks of gestation: the period of organogenesis. Generally speaking, a dose of < 10 rad (<0.1 Gy) to the implanted embryo does not result in a significant increase in the incidence of congenital malfor-mations, intrauterine growth retardation, or fetal death. It is important to keep in mind that approximately 30% to 50% of human embryos abort spontaneously. Further, human infants have a 2.75% major malformation rate at term, which rises to approximately 6%-10% once all malformations and genetic diseases become manifest.34-38 In general, the maximum theoretical risk to the human embryo exposed to doses of < 5 rad (< 0.05 Gy) is extremely small. The risk from diagnostic radiation should be evaluated, then, in light of the significant risks inherent in a normal pregnancy. As a general rule, a direct beam film, (abdomen, pelvis, or lumbar spine) yields 1 rad (0.05 Gy), whereas an indirect beam film (skull, chest, or extremities) yields 0.1 rad (.001 Gy) The total exposure for a CT scan of the abdomen, for example, is estimated to be 15-20 mSv. Other variables that affect the complete dosimetric evaluation are shielding, exposure time, and tube-to-film distance. Contrast agents are considered safe for mother and fetus although attention to maternal hydration is recommended.

Necessary radiographic examination should proceed with the following guidelines:

Order the minimum number of radiographs to obtain the maximum information. Careful planning prevents duplication.

Shield the abdomen with a lead apron. This reduces fetal exposure by a factor of eight.

When many radiographs are required over a long period of time, a thermoluminescent dosimeter or “radiation badge” may be attached to the patient to serve as a guide for dosage delivered. This is particularly valuable for the critically ill patient who may have a prolonged ICU length of stay.

The term, abruptio placentae, or, placental abruption, denotes the abnormal separation of the placenta after the 20th week of gestation, hence creating a loss of area for exchange of respiratory gases and nutrients for the fetus. Perinatal death is most often due to anoxia, prematurity or exsanguination. Because of the extensive pathway of dissection, the amount of blood that appears through the cervix may be small and does not reflect the urgency of the situation. Aside from vaginal bleeding, other signs and symptoms of placental abruption include abdominal pain, uterine tenderness and contractions. One of the most serious complications is disseminated intravascular coagu-lation (DIC), the etiology of which is postulated to be entry of thromboplastins from the injured placental site into the maternal circulation. Once the diagnosis is suspected, a plan for expedient delivery is implemented.

Placenta previa is the implantation of the placenta in the lower uterine segment prior the fetal presenting part. The most common presenting sign is painless bleeding in the second or third trimester. Both transvaginal and transabdom-inal sonography are highly diagnostic because the internal cervical os is readily identified. Expectant management to maximize fetal maturity is reasonable, however in the pres-ence of significant hemorrhage, delivery is advocated.

The ruptured gravid uterus, a catastrophic event, carries a high mortality rate for both mother and fetus. The rupture commonly occurs at a uterine scar site. Primary repair or placement of a Gore-Tex patch is possible for small areas, however extensive rupture with large blood loss requires hysterectomy.

Uterine rupture may occur in situations in which the mecha-nism of injury is extremely forceful. A study of primates subjected to acute deceleration injuries showed marked increases in uterine pressure prior to rupture. Uterine rupture is commonly manifested by uterine tenderness and severe maternal shock. Plain radiographs may show fetal parts extruding beyond the confines of the normally intact uterus.

Prevention measures such as three-point automobile restraint systems have been demonstrated in animal models



to significantly increase fetal survival from 50% to 92% as reported by Crosby et al. Crosby and Costiloe, in a review of 208 pregnant victims of motor vehicle crashes, found that the most common cause of fetal death was maternal death. In these cases, ejection from the vehicle was common, so restraint devices were of proven value to decrease maternal and fetal mortality. Wolf and colleagues conducted a review of 1,243 restrained and 1,349 unrestrained pregnant patients to determine the effect of seat-belt use on pregnancy out-come. Unrestrained drivers were 1.9 times more likely to give birth to low weight infants and 2.3 times more likely to deliver within 48 hours of injury.

SUMMARY

A coordinated, team approach by the trauma, orthopedic, and gynecologic surgeons, as well as by the interventional radiologist and physical therapist, is required to optimize the outcome following these life-threatening injuries.

REFERENCES

1. Sachs BP, Brown DAJ, Driscoll SG, et al. Maternal mortality in Massachusetts. N Engl J Med. 1987;316:667.

2. Kissinger DP, Rozycki GS, Morris JA Jr., et al. Trauma in pregnancy: predicting pregnancy outcome. Arch Surg. 1991;126:1079.

3. Pearlman MD, Tintinalli JE, Lorenz RP. A prospective con-trolled study of outcome after trauma during pregnancy. Am J Obstet Gynecol. 1990;162:1502.

4. Brent RL. The effect of embryonic and fetal exposure to X-ray, microwaves, and ultrasound: counseling the pregnant and nonpregnant patient about these risks. Semin Oncol. 1989;16:347.

5. Rozycki GS, Ochsner MG, Jaffin JH, Champion HR. Prospective evaluation of surgeons’ use of ultrasound in the evaluation of trauma patients. J Trauma. 1993;34:516.

6. Esposito TJ, Gens DR, Smith LG, et al. Trauma during preg-nancy: a review of 79 cases. Arch Surg. 1991;126:1073.

7. Buchsbaum HJ. Accidental injury during pregnancy. Contemp Obstet Gynecol. 1982;20:27.

8. Crosby WM. Trauma during pregnancy: maternal and fetal injury. Obstet Gynecol Surv. 1974;29:683.

9. Crosby WM, Costiloe J. Safety of lap-belt restraint for pregnant victims of automobile collisions. N Engl J Med. 1971;284:632.

10. Curet MJ, Schermer CR, Demarest GB, Bieneik EJ, Curet LB. Predictors of outcome in trauma during pregnancy: iden-tification of patients who can be monitored for less than 6 hours. J Trauma. 2000;49:18-25.

57

SIMULATION IN TRAINING AND TESTINGOF PREHOSPITAL EMERGENCY RESPONDERS

Joseph A. Scott MD;1 S. Barry Issenberg MD2

1 Center for Research in Medical Education University of Miami School of Medicine, Miami, Florida2 Center for Research in Medical Education University of Miami School of Medicine, Miami, Florida


SUMMARY

Professional competence is a primary goal of prehospital provider education. This competency is complex and includes a wide variety of tasks including integrating theory with performance of tasks, demonstrating commu-nication skills, understanding one’s local environment and anticipating change. Simulation can facilitate traditional training and assessment methods to achieve this goal. Simulation methods provide a wide variety of conditions and experiences, a safe environment that is learner-focused and mistake forgiving and training that is reproducible, standardized and objective. Challenges with the use of simulation include financial costs, human resources and the expertise to develop a robust curriculum. Adopting a curriculum development model will help to ensure the successful integration of simulation into training programs. Training evaluation using simulation can have a very positive effect on learner self-efficacy. The University of Miami’s Emergency Response to Terrorism course is an example of how simulation can be integrated into a prehos-pital provider training curriculum.

Key wordsSimulation, Prehospital, Paramedic, EMT, Education, Emergency, Terrorism, Skills, Assessmen.

RESUMEN

La capacidad professional es el objetivo principal del entre-namiento de personal de primeros auxilios. Esta es compleja y consiste en la integración de la teoría con la práctica, buena comunicación verbal, previsión de posibles cambios y demás. En el logro de este objetivo, la simulación puede complementar los métodos de entrenamiento y evaluación tradicionales. La simulación proporciona exposición a múltiples condiciones y experiencias en un marco seguro, enfocado en el alumno, indulgente con sus errores, repro-ducible, uniforme, objetivo, con un efecto muy positivo sobre la confianza del estudiante en si mismo. El desafío al uso de la simulación incluye su costo y los recursos humanos y experiencia necesarios para desarrollar un cur-rículo robusto. La adopción de un modelo para el desarrollo del currículo ayuda a garantizar la integración exitosa de la simulación con los programas de entrenamiento. El curso de Respuesta de Emergencia al Terrorismo de la Universidad de Miami es ejemplo de la integración de la simulación con un currículo de personal de primeros auxilios.

PREHOSPITAL PROVIDER EDUCATION

In 1998, the United States National Highway Traffic Safety Administration (NHTSA) proposed that one of the primary outcomes of prehospital provider education should be professional competence (1). While traditional educational outcomes focused on a specific set knowledge and skills that prehospital providers should master, the training and assessment of professional competence is much more chal-

lenging. For example, six components have been identified that comprise professionalism (Table 1). Including these three individual and three team components in prehospital training requires educators to develop and use different resources to teach and evaluate this important competency.

Table 1. Professional CompetenceComponent Description

Individual Conceptual Understand theoretical foundationsTechnical Task performanceIntegrative Practice of theory of skills

Team Interpersonal Written & oral communicationContextual Understanding local societal

environmentAdaptive Anticipate & accommodate change



While integrating these components is a challenge in any edu-cational and clinical setting, ensuring professional competence in the setting of complex trauma is especially difficult because of the acute, uncontrolled nature of the clinical experience.

RECENT LITERATURE

Recent literature has discussed the inadequate emphasis on skill training in the prehospital environment (2) and the lack of correlation between the number of didactic training hours and paramedic certifying examination performance (3). Additionally, medical errors may result in a signifi-cant number of deaths annually in the United States (4). Simulation has been recognized for nearly 30 years in the airline industry as an effective method of training to reduce errors, and has recently gained acceptance in the healthcare professions. NHTSA now recommends that instruction of emergency medical technicians (EMTs) and paramedics utilize simulation and scenario-based skills labs in the pur-suit of professional competence (1).

BENEFITS AND DISADVANTAGES

In today’s world of five-minute office visits, reduced hospital stays, and increased litigation, healthcare is appropriately more patient focused with less time available for teaching and evaluating trainees. Moreover, prehos-pital emergency responders have fewer opportunities to develop and hone their skills in controlled environments. This is especially true with critical, life-saving skills that may be used infrequently such as those required in trauma situations. On the other hand, simulation provides a safe environment that is mistake forgiving, an opportunity for practice and feedback, and is focused on the trainee rather than a live, sick patient. Manipulation of time, either by quickening or slowing the pace of the scenario, can ben-efit the learner. Scenarios can be constructed to promote critical thinking and team building. Additionally, simula-tion provides a reproducible, standardized, and objective method for training and evaluating learners that is difficult to provide with live patients. All of these attributes enhance the process of adult learning that is essential to the success of prehospital emergency responder training.

There are several factors to keep in mind when making the decision to integrate simulation-based education and evalu-ation into an existing training program. The cost of simula-tion is not inconsequential. Equipment prices range from less than one hundred to hundreds of thousands of dollars. Faculty demands may increase in order to provide adequate instruction and feedback. Technical or software upgrade and maintenance costs must also be considered (5). While having many benefits, simulation does not replace the clinical expe-

rience. As demonstrated in a study of Advanced Trauma Life Support (ATLS) training, trauma management skills of novice surgeons do improve with the use of simulation but do not reach the level of experienced practitioners (6).

SIMULATION-BASED CURRICULUM DEVELOPMENT AND IMPLEMENTATION

Too often, a simulator purchased with the best intentions quickly collects dust because of the challenge of developing a new curriculum that includes integration of the new tool. A working understanding of curriculum development will ensure that simulation methods are implemented effectively and achieve their maximum benefit to the training program. The basic steps for curriculum development follow:

• Determine the learning outcomes you want your trainees to achieve (for example the components of professional competence listed in Table 1).

• Choose the assessment method(s) that will ensure these outcomes are achieved (multiple-choice exams for cognitive and problem-solving outcomes, simulation scenarios involving checklists and ratings for tasks and team-communication outcomes).

• Determine the most appropriate learning strategy for each outcome (lectures for theoretical outcomes; tabletop, mannequin-based simulations for tasks and integrating theory and skills)

Following the above steps will ensure that when the cur-riculum content is developed, it is fully aligned with the outcomes, assessment tools and learning strategies.

Once the curriculum is developed, incorporate proven edu-cational models to maximize the use of simulation-based training. For example, structure the training sessions to allow for deliberate practice. As defined by Ericsson, this is the most important factor separating an elite performer from a novice (7). Identify a well-defined task that is an appropriate level of difficulty for the learner. Guide the learner through the task and provide informative feedback. Now, provide time for repetition with feedback so that the learner can correct any errors made. This repetitive practice using simulation and feedback is integral to the development of competence.

SIMULATION FIDELITY

Frequently, the complexity of the simulation chosen is not important. Low-fidelity simulation models such as case-based questions on written examinations, tabletop exercises, and simple CPR manikins can be as effective as high-fidelity simulations involving standardized patients, computer-controlled manikins and virtual reality (8, 9).

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Engineering fidelity adds realism to the scene. This can be as simple as intravenous catheter (IV) arms that bleed upon venipuncture or as complex as full-body simulators that breathe and respond with appropriate changes in vital signs upon medication administration. More important, achieving psychological fidelity, the suspension of disbelief by the learner, is the ultimate goal. Ideally, a combination of multiple simulation modalities is used to maintain learner interest and foster deliberate practice.

A TRAINING EXAMPLE

Emergency Response to Terrorism (ERT) is a 16-hour, 2-day course developed by The University of Miami Center for Research in Medical Education (CRME). The goal of the curriculum is to teach emergency responders how to protect themselves in the case of a terrorist attack and, simultaneously, achieve the greatest good for the greatest number of victims. Learning objectives include learning how to initiate incident operations, implement personal and public safety protective measures, perform appropriate decontamination, initiate command with effective commu-nication, and provide needed medical care.

The curriculum was developed to support these objectives, develop mastery of needed skills, and to practice team work under difficult conditions. Skills include emergent donning of personal protective equipment (PPE), IV placement and endotracheal intubation while wearing PPE, effective command and communication, triage, decontamination of ambulatory and incapacitated victims, emergent medical treatment of victims with vesicant and blast injuries, and administration of nerve agent and cyanide antidote kits.

While some didactic lectures are necessary to build a fund of knowledge with respect to the above objectives, learners spend the majority of time rotating in small groups through interactive skill stations, scenarios, and exercises. Student-to-instructor ratios are kept low to facilitate interaction, feed-back, and evaluation. Each exercise builds on a previous one. For example, one of the first exercises is emergent donning of Level C PPE (air-purifying respirator, chemical-protec-tive suit, chemical-resistant gloves and boots) with learners working together in pairs. Throughout the remainder of the course, in skill stations and scenarios, participants are required to repetitively don PPE under the guidance of instructors and classmates, receiving feedback as needed.

Skills stations on the first day of the course, such as set-ting up decontamination equipment, using antidote kits, establishing IVs, and intubating while wearing PPE, are reinforced with scenarios on the second day that require these skills once again.

Simple IV arms and intubation heads are used in one sta-tion. Actual decontamination showers are used in another. Full-body manikins are disrobed and washed repeatedly to practice decontamination of non-ambulatory victims. A trauma manikin, complete with bleeding amputation, is used to simulate a victim of a radiation dispersal device. Another manikin is outfitted with a mask to simulate the cholinergic effects of a nerve agent. Videos of different victims are shown at 30-second intervals to practice triage skills. A standardized patient (SP) with moulage simulates a vesicant victim during a scenario. Actual radios are used to commu-nicate during a tabletop exercise. A television game show format is used to quiz participants about PPE equipment.

During all these exercises, instructors use specific check-lists, developed for each skill and scenario, to evaluate the learners and provide effective feedback. Furthermore, group members who may not be actively participating in a skill at a specific time period are asked to constructively critique their team members. Pre and postcourse, scenario-based, multiple-choice-question, written examinations evaluate cognitive learning and problem solving. In short, multiple simulation modalities are used to promote deliberate prac-tice of required skills and assess learning.

EVALUATION OF TRAINING

Testing

Simply reformatting present written examinations into case-based questions adds an element of simulation to the testing procedure. As illustrated above, developing simple checklists allows one to easily evaluate skill performance using simulation. The use of checklists and high-fidelity simulators has been shown to be effective in the individual testing of trauma management skills after an ATLS course (10). Trauma team performance has also been evaluated in a similar fashion, with success, using simulation (11).

In addition to testing the individual or team, simulation can also effectively evaluate the educational process. Quality improvement projects can be developed based on the results of pre- and postcourse simulation testing (12). The University of Miami ERT course adopts a combination of all of these modalities and always includes direct-learner feedback.

Self-Efficacy

While not always considered when discussing professional competence, self-efficacy (SE), the confidence one has to perform a given behavior, has previously been shown to be highly predictive of performance (13). The use of simula-tion in trauma scenarios produces significant improvement



in perceived preparedness and SE amongst many levels of healthcare providers (13). Additionally, simulation use can achieve equal learner satisfaction when compared with the examination of live patients (14).

CONCLUSIONS

Simulation should be incorporated into most prehospital training and testing. When used appropriately, it is learner focused, mistake forgiving, reproducible, and allows for deliberate practice. It answers the need for standardized training and evaluation of emergency providers and fosters the adult learning process. It can be easily implemented in a training program, and used to evaluate the education process as well, if the following recommendations are followed:

• Develop the outcomes, assessment tools and learning strategies

• Develop the content that will align outcomes assessment and learning strategies

• Select the most appropriate simulation modality that fulfills the curricular needs

• Incorporate deliberate practice into training sessions• Use a variety of evaluation tools such as checklists to not

only document skill performance but also evaluate the effectiveness of your training program.

Using simulation can be very rewarding for instructor and learner alike and will provide the confidence necessary to achieve professional competence.

REFERENCES

1. National Highway Traffic Safety Administration National Standard Curriculum for EMT-Paramedic, 1998.

2. Pollock MJ, Brown LH, Dunn KA. The perceived importance of paramedic skills and the emphasis they receive during EMS education programs. Prehosp Emerg Care. 1997;1(4):263-8.

3. Cannon GM Jr, Menegassi JJ, Margolis GS. A comparison of paramedic didactic training hours and NREMT-P examina-tion performance. Prehosp Emerg Care. 1998;2(2):141-144.

4. Kohn LT, Corrigan JM, Donalson, MS. To Err is Human: Building a Safer Health System. 2000; National Academies Press, Washington D.C.

5. Issenberg SB, McGaghie WC, Hart IR, et al: Simulation technology for health care professional skills training and assessment. JAMA 1999;282(9):861-6.

6. Marshall, RL, Smith JS, et al. Use of a human patient simu-lator in the development of resident trauma management skills. J. Trauma 2001;51(1):17-21.

7. Ericsson KA. Krampe RT, Tesch-Romer, C. The role of deliberate practice in the acquisition of expert performance. Psychol Rev 1993;100(3):363-406.

8. Agazio, JB, Pavlides CC et al. Evaluation of a virtual reality simulator in sustainment training. Mil Med 2002;167(11):893-7.

9. Gilbart MK, Hutchison CR et al: A computer-based trauma simulator for teaching trauma management skills. Am J Surg. 2000;179(3):223-8.

10. Ali J, Gana TJ, Howard M. Trauma Mannequin assessment of management skills of surgical residents after advanced trauma life support training. J Surg Res 2000; 93(1):197-200.

11. Holcomb JB, Dumire RD, Crommett JW, et al: Evaluation of trauma team performance using an advanced human patient simulator for resuscitation training. J. Trauma 2002; 52(6):1078-86.

12. LaCombe DM, Gordon DL, Issenberg SB, Vega AI. The Use of Standardized Simulated Patients in Teaching and Evaluating Prehospital Care Providers. Am J of Anesthesiol 2000;4:201-4.

13. Treloar D, et al: On-site and distance education of emergency medicine personnel with a human patient simulator. Mil Med 2001;166(11):1003-6.

14. Salen P, O’Connor R, et al. FAST education: A comparison of teaching models for trauma sonography. J Emerg Med 2001;20(4):421-5.

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Autores: Carlos A. Ordóñez D. MDRicardo Ferrada D. MDRicardo Buitrago B. MD

Edición: 2007Pasta: DuraFormato: 21,5 x 27,9 cm

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CUIDADO INTENSIVOY TRAUMA

Autores: Ricardo Ferrada, MDAurelio Rodríguez, MDAndrew Pietzman, MDJuan Carlos Puyana, MDRao Ivatury, MD

Edición: 2007Pasta: DuraFormato: 21,5 x 27,9 cm

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