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recovery programs has prompted a re-evaluation of surgicalfluid management. These programs employ a multimodal

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160tricted.1 In contrast, Shires et al in the 1960s2 focused oneffects of fluid redistribution, with third space losses

pleting intravascular volume. Despite conflicting studiesthe exact alterations in extracellular fluid volume in re-nse to trauma,3 this work led to the dogma that intrave-

us fluid and sodium administration in excess of normalintenance requirements were necessary in the periopera-e period to maintain tissue perfusion and oxygenation.Shoemaker et al were the first to show that critically illtients fared better when their cardiac output and oxygenlivery were increased above normal values and this works then continued to include high-risk surgical patients.4,5

approach to perioperative care aiming to modify the homeo-static response to surgical trauma, and while the beneficialeffects (wound healing and resolution of inflammation)should be preserved, the more undesirable effects are atten-uated. Hemorrhage and intravascular hypovolemia are initi-ators of the stress response by the stimulation of volume andpressure receptors, which activate the central nervous sys-tem. The response tends to be proportionate to the amount ofshock; both the degree and the duration of blood volumedeficit, therefore, are important determinants of the degree ofphysiological response to injury. Also, since hemorrhage andhypovolemia decrease cardiac output, tissue ischemia mayresult. This is another important activator of physiologic re-sponses to injury, not only because it may potentiate activa-tion of the centrally mediated stress responses, but also be-cause it leads to initiation of local responses, mediator

artment of Colorectal Surgery, Freeman Hospital, Newcastle UponTyne, Tyne and Wear, UK.ress reprint requests to Alan F. Horgan, MD, Department of Colorectalerioperative Fluid Managephie E. Noblett, MD, FRCS, and Alan F. Hor

With the introduction of enhanced surgical rinterest over recent years in the optimal sbetween liberal vs restrictive fluid regimens hualized goal-directed therapy has been introized controlled trials. While untreated hypooverload can be just as (if not more) hazarindividual patients needs using a treatmenvariables, postoperative recovery can be imptestinal dysfunction, and reduced hospital stSemin Colon Rectal Surg 21:160-164 CrownAll rights reserved.

istory of Perioperativeuid Managementhe bodys fluid and electrolyte balance is kept within atightly defined range mainly by the action of antidiuretic

rmone and the renin-angiotensin-aldosterone axis. In therioperative period preoperative fasting, bleeding, and in-sible losses reduce extracellular volume. Activation of theammatory cascade increases capillary permeability, de-ting intravascular volume, with the resulting increasedue oncotic pressure further exacerbating the fluid loss.ese reductions in intravascular volume trigger a number ofysiologic responses. Moore described the net effect of therelSurgery, Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, UK.E-mail: Alan.Horgan@nuth.nhs.uk

1043-1489/$-see front matter Crown Copyright 2010 Published by Elsevierdoi:10.1053/j.scrs.2010.05.007entMD, FRCS

ry programs there has been a rekindledl fluid regimen. The historical debateen re-evaluated and the idea of individ-and subjected to a number of random-ia can be detrimental to patients, fluidBy tailoring fluid administration to anrithm based on closely monitored flowwith reduced morbidity, less gastroin-

right 2010 Published by Elsevier Inc.

is prompted several trials using combinations of fluids andtropes to study the effects of improving tissue oxygen

livery in surgical patients.6-8 These studies found that pa-nts in the intervention groups who had received more fluidibited reduced mortality and morbidity when compared

th the control patients. However, it remains unclearether the benefits seen were due to the inotropes, or thera fluid received by the intervention patients. Similarly thetrolled study environment, often involving admission to a

tical care facility, complex monitoring, and differing tar-s, add to the complex interaction of factors that may haveuenced the resultant outcomes.

Over the past decade, the evolution of enhanced surgicalease, and cell activation.It is clear therefore that optimizing hemodynamic status in

Inc. All rights reserved.

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Perioperative fluid management 161perioperative period may have profound effects on sur-al outcome by direct maintenance of organ perfusion andmodulation of the inflammatory response to injury. How-r the problems of fluid overload and its related complica-

ns should not be underestimated.

azards of aberal Fluid Regimenreased aldosterone and antidiuretic hormone release fol-ing surgery led to conservation of water and sodium as an

egral component of the stress response.1 With liberal in-venous fluid administration in addition to this naturaless response, patients can be at risk from overhydration.ministration of excess fluid may contribute to significantstoperative morbidity with affects on several organ sys-s: cardiac function, respiration, the coagulatory system,

d the gastrointestinal tract.9-11 The sequelae of fluid over-d are often the result of fluid shifts, with accumulation ofid in potential spaces, particularly those of the bowel wall,ritoneum, and pleural cavities. These third space losses arearticular problem after major abdominal surgery and haveen shown to increase with intravenous fluid therapy.12

Holte et al13 illustrated the potential detrimental effects ofess fluid by subjecting healthy volunteers to 1 of 2 fluid

ministration regimens. They found significant weight gaind worsened spirometry readings in the group given liberalids. In a study assessing deaths from pulmonary edema injor inpatient surgery, 7.6% of patients developed pulmo-

ry edema with an associated mortality of 11.9%. Net fluidention of 67 ml/kg/d was found to be a predisposingtor in those patients affected.14 Similarly, weight gain of0% over baseline has been correlated with increased post-

erative morbidity.10 Certainly, in thoracic surgery there is and toward a dry regimen, with evidence to suggest thisuces postoperative pulmonary complications.15

Excess fluid volume may increase cardiac work and myo-dial oxygen demands. The Starling myocardial perfor-nce curve shows that until a certain point intravascular

lume expansion increases cardiac output due to increasedd-diastolic filling. Beyond that point, further fluid admin-ation will lead to reduced ventricular function. In a largeservational study of patients undergoing major noncardiacgery, those patients who underwent pulmonary arteryheterization and increased fluid administration had arked increase in cardiac morbidity. Compared with thetrol group, it is unclear, however, how much of the post-

erative outcome could be attributed to the fluid adminis-tion alone.16

Excretion of administered intravenous fluid relies on ade-ate renal function; thus, in overhydration, excess demandsplaced on the kidney. A study of overhydrated burn pa-

nts showed that only 50% of patients had excreted theess volume at 1 week.17 Even in healthy volunteers, ex-

tion of an acute saline bolus (22 ml/kg) takes severalys.18 While functional demand on the kidney may be in-

comfluased, there is no clear evidence of the role of fluid excesspostoperative renal morbidity in isolation.

Tissue edema in the gut wall impairs bowel motility, im-irs gastric emptying, and predisposes to postoperative il-s, prolonging hospital stay.9 Indeed, gastrointestinal dis-bance is 1 of the commonest morbidities recorded afterjor abdominal surgery with local effects of prolonged nau-and vomiting with enteric nutritional intolerance. More

bally, however, the gut mucosal edema and prolongedus may allow translocation of bacteria and endotoxin, fur-r driving the systemic inflammatory response and con-

buting to multiple organ dysfunction and sepsis. Large-lume fluid sequestration in the peritoneal cavity togetherth bowel wall and luminal fluid associated with ileus, canextreme cases result in abdominal compartment syn-me, with concomitant effects on respiratory and renalction.

olution of Fluid Restrictione increasing interest in strategies to improve postoper-ve outcome on the back of enhanced surgical recoverygrams called for the traditional aggressive approach to

rioperative fluid administration to be re-evaluated. Tak-the lead from thoracic surgical practice, Kehlet and col-

gues introduced the concept of fluid restriction in his fastck surgical regimens with intraoperative fluid standard-d to 2 L (1500 mL isotonic saline 500 mL 6% hydroxy-yl starch).19

A large multicenter study comparing standard and restric-e fluid regimens in patients undergoing colorectal surgerynd a marked reduction in morbidity rate of 21% versus

% in the restricted group.20 In contrast, however, a largedy of 80 patients under going colorectal surgery random-d to either a restricted or a standard regimen found day ofgery intravenous fluid to be 2 vs 2.75 L in the restricted

d standard groups, respectively.21 This study failed tow any significant improvement in outcome with a moretrictive regimen; however, it did provide evidence thatre were no adverse effects to patients subjected to fluidtriction. The standard group in the Brandstrup study,wever, received a median of 5388 mL intravenous fluid on

day of surgery with a range of 2700-11,083 mL. It isssible that more patients in this group experienced com-cations from overhydration, in what was clearly a ratheret standard regimen.20 Certainly, animal studies havewn that excess crystalloid administration has a significant

pact on functional and structural intestinal anastomoticbility.22

There are now numerous studies in colorectal surgery ander surgical specialties showing patients fared better whenids are administered in a restricted manner.23-25 Even saltd water administration within an accepted normal ranges been linked with increased morbidity, with a study oftients undergoing colorectal resection showing fewer com-cations following mean daily sodium doses of 115 mmolpared with 149 mmol.26 So should we conclude thatid restriction in elective surgery is beneficial?

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162 S.E. Noblett and A.F. Horganurrenterspective: Individualizedoal-Directed Therapye great fluid debate of whether patients should be treatedth a restricted or liberal fluid regimen has now been ex-nded to include a third optiongoal-directed therapy.is theory accepts that there are clear benefits to givingravenous fluid, allowing maintenance of tissue perfusionexes and oxygenation (agreeing with the liberal fluid ar-

ment); however, it also accepts there are definite risks andverse events associated with overhydration (agreeing with

restrictive regimen promoters). Figure 1 suggests howth these arguments may interact. If the relationship be-een volume load (x-axis) and morbidity (y-axis) is plotteda U-shaped curve, we can see that too little fluid withue hypoxia would be related to increased morbidity asuld too much fluid; the nadir of this curve represents thee of optimization. The key here is that both the restrictive

d the liberal studies to date have still followed genericcipe approaches to fluid administration using plannedlume per kilogram per hour of crystalloid through theration of surgery. Patient perioperative monitoring in mostrk consists of pulse, mean arterial pressure, central venousssure, and urine output being used to assess volume sta-. There is, however, no evidence that static measurementspressure are adequate detectors of tissue hypoperfusion;tainly it is well-established that hypovolemia may be

re 1 Curve A represents the hypothesized line of risk relation-p between volume load and morbidity. Broken line B representsivision between patient groups in a wet vs dry regimen. Brokene C represents a division between patients and groups in a goal-ected vs nonoptimized study. The nidus of the curve is thetimization zone.45 Reprinted with permission from Oxford Uni-sity Press. (Color version of figure is available online.)sent despite normal systemic and filling pressures.27,28

id management strategies based on targeted flow variablesproileher than targets of simple filling pressures are more suc-sful.29,30

This realization has led to a new body of evidence usingtocolized fluid algorithms based on flow parameters to

ide fluid therapy on an individual patient basis. Manydies have been carried out assessing the role of goal-di-ted therapy and have employed a variety of monitoringhniques. Early studies used pulmonary artery cathetersd targeted cardiac index and/or oxygen delivery in the pre-intraoperative period.6,8,31,32 These studies have demon-ated potential benefits from goal-directed fluid administra-n. Boyd et al6 increased oxygen delivery using dopexamineusion and found a reduction in 60-day mortality and mor-ity in a group of high-risk surgical patients. Wilson et al8

nd similar results using combinations of fluids and ino-pes; however, on further study they found similar resultsld be obtained from fluids alone. Lobo et al32 randomizedpatients undergoing major surgery to receive fluids and

butamine to achieve supranormal cardiovascular values.ey found a reduced mortality, fewer complications, and and toward less organ dysfunction in the intervention pa-nts. With the inherent risks of pulmonary artery catheter-tion, and patients requiring critical care admission forir use, practically, this type of monitoring is not feasibleroutine use in elective surgical patients. Further studies

ve therefore looked at intraoperative optimization usingre minimally invasive techniques, such as esophagealppler monitoring. In 1995, Mythen and Webb33 random-d patients undergoing cardiac bypass surgery to receiverioperative plasma volume expansion using colloid andnd a reduction in gut mucosal hypoperfusion and im-ved outcome in the intervention group. Studies in other

tient groups have confirmed potential benefits in terms ofrbidity and hospital stay following perioperative optimi-ion.34-36 Studies on patients undergoing major colorectalections have shown a significantly increased cardiac out-t, reduced critical care admission, with reduced morbidity,proved recovery of gastrointestinal function, and reducedspital stay following goal-directed fluid administra-n.37-39 Additionally, significantly reduced serum interleu--6 (as a marker of the systemic inflammatory response togical trauma) was found in a group of colorectal patientso had undergone a fluid optimization regimen com-

red with standard care.39 Studies of general surgical pa-nts (mean age 55-60 years) had a reduced stay of 2 days;diac surgical patients (mean age 65 years) had a reducedy of 4 days, and fractured neck of femur patients (mean age-85 years) had a reduced stay by 4-8 days.33-36 In patientsincreasing age and comorbidity, the importance of accu-e perioperative fluid management is even greater, withtentially increased benefits of a goal-directed regimen.Goal-directed or fluid optimization regimens in pa-nts undergoing major abdominal surgery have now beenjected to systematic review and meta-analysis, confirmingt goal-directed, flow-guided optimization results in im-

ved hemodynamic control, reduced morbidity, reduced

us, and shorter hospital stays.40,41

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Perioperative fluid management 163he Future oferioperative Fluid Managementravenous fluids are medications. As such, they are proba-the most widely prescribed drug in hospital medicine yetrationale behind what fluid, how much, and when con-

ues to be debated in surgical practice. Fluid prescriptiond administration is often carried out by a recipe-bookproach to a given operation or clinical situation with littleard to the individual patient and physiologic response. It

eds to be stressed to doctors and all involved in patient caret intravenous fluids, while often not considered as drugs,not benign medications. Indeed, in the UK the report ofNational Confidential Enquiry into Perioperative Death

hlighted overhydration as a major contributory factor inevolution of postoperative complications causing death.42

arge US study found over 8000 postoperative deaths perr were attributed to pulmonary edema in the absence of

y other cause except excess intravenous fluid therapy.43 Inponse to this and with the increasing evidence to supportal-directed therapy, the British Consensus Guidelines onravenous fluid therapy for adult surgical patients now statet, for patients undergoing some forms of orthopedic and

dominal surgery, intraoperative fluids should be adminis-ed to monitored and targeted optimal stroke volume touce morbidity.44

Surgical fluid management aims to avoid tissue hypoper-ion, activation of the systemic inflammatory response, andltiple organ failure yet at the same time prevent fluid

erload. Judicious perioperative fluid therapy can improvetcome after major surgery; however, accurate fluid optimi-ion requires careful cardiovascular monitoring. Ideal in-operative fluid management is tailored to the individualtient and involves monitoring of flow-based parameters byinimally invasive technique with little risk. Simply using

ra monitoring, however, is not enough. A proactive ap-ach to goal-directed therapy following a treatment algo-m will allow most patients to achieve their individualtimized hydration state, allowing maximum tissue per-ion and oxygenation while protecting them from the risksvolume overload. Goal-directed fluid management has

en shown to reduce morbidity and improve outcome inny surgical disciplines and is an important component ofhanced recovery after surgery programs.

ferencesMoore FD: Metabolic Care of the Surgical Patient. Philadelphia, WBSaunders, 1959Shires T, Willliams J, Brown F: Acute changes in extracellular fluidsassociated with major surgical procedures. Ann Surg 154:803-810,1961Nielson OM, Engell HC: Extracellular fluid volume and distribution inrelation to changes in plasma colloid osmotic pressure after major sur-gery. A randomised study. Acta Chir Scand 151:221-225, 1985Shoemaker WC, Montgomery E, Kaplan E, et al: Physiologic patterns insurviving and nonsurviving shock patients. Use of sequential cardiore-

spiratory variables in defining criteria for therapeutic goals and earlywarning of death. Arch Surg 106:630-636, 1973Shoemaker WC, Appel P, Bland R: Use of physiologic monitoring topredict outcome and assist in clinical decisions in critically ill post-operative patients. Am J Surg 146:43-50, 1983Boyd O, Grounds RM, Bennett ED: A randomised clinical trial of theeffect of deliberate perioperative increase of oxygen delivery on mor-tality in high-risk surgical patients. JAMA 270:2699-2707, 1993Stone MD, Wilson RJT, Cross J, et al: Effect of adding dopexamine tointraoperative volume expansion in patients undergoing major electiveabdominal surgery. Br J Anaesth 91:619-624, 2003Wilson J, Woods I, Fawcett J, et al: Reducing the risk of major electivesurgery: randomised controlled trial of preoperative optimisation ofoxygen delivery. BMJ 318:1099-1103, 1999Lobo DN, Bostock KA, Neal KR, et al: Effect of salt and water balance onrecovery of gastrointestinal function after elective colonic resection: arandomised controlled trial. Lancet 359:1812-1818, 2002Lowell JA, Schifferdecker C, Driscoll DF, et al: Postoperative fluid over-load: not a benign problem. Crit Care Med 18:728-733, 1990Holte K, Sharrock NE, Kehlet H: Pathophysiology and clinical impli-cations of perioperative fluid excess. Br J Anaesth 89:622-632, 2002Chan ST, Kapadia CR, Johnson AW, et al: Extracellular fluid volumeexpansion and third space sequestration at the site of small bowelanastomoses. Br J Surg 70:36-39, 1983Holte K, Jensen P, Kehlet H: Physiologic effects of intravenous fluidadministration in healthy volunteers. Anesth Analg 96:1504-1509,2003Areiff AI: Fatal postoperative pulmonary edema: pathogenesis and lit-erature review. Chest 115:1371-1377, 1999Slinger PD: Perioperative fluid management for thoracic surgery: thepuzzle of postpneumonectomy pulmonary oedema. J CardiothoracVasc Anesth 9:442-451, 1995Polanczyk CA, Rohde LE, Goldman L, et al: Right heart catheterizationand cardiac complications in patients undergoing noncardiac surgery:an observational study. JAMA 286:309-314, 2001Gump FE, Kinney JM, Iles M, et al: Duration and significance of largefluid loads administered for circulatory support. J Trauma 10:431-439,1970Drummer C, Gerzer R, Heer M, et al: Effects of an acute saline infusionon fluid and electrolyte metabolism in humans. Am J Physiol 262:F744-F754, 1992Basse L, Jakobsen DH, Billesbolle P, et al: A clinical pathway to accel-erate recovery after colonic resection. Ann Surg 232:51-57, 2000Brandstrup B, Tonnesen H, Beier-Holgersen R, et al: Effects of Intrave-nous Fluid Restriction on Postoperative complications: comparison oftwo perioperative fluid regimens. Ann Surg 238:641-648, 2003Mackay G, Fearon K, McConnachie S, et al: Randomized clinical trial ofthe effect of postoperative intravenous fluid restriction on recovery afterelective colorectal surgery. Br J Surg 93:1469-1474, 2006Marjanovic G, Villian C, Juettner E, et al: Impact of different crystalloidvolume regimes on intestinal anastomotic stability. Ann Surg 249:181-185, 2009Joshi GP: Intraoperative fluid restriction improves outcome after majorelective gastrointestinal surgery. Anesth Analg 101:601-605, 2005Kita T, Mammoto T, Kishi Y: Fluid management and postoperativerespiratory disturbances in patients with transthoracic esophagectomyfor carcinoma. J Clin Anesth 14:252-256, 2002Bergman S, Feldman L, Carli F, et al: Intraoperative fluid managementin laparoscopic live-donor nephrectomy: challenging the dogma. SurgEndosc 18:1625-1630, 2004Tambyraja AL, Sengupta F, Macgregor AB, et al: Patterns and clinicaloutcomes associated with routine intravenous sodium and fluid admin-istration after colorectal resection. World J Surg 28:1046-1051, 2004Hamilton-Davies C, Mythen MG, Salmon JB, et al: Comparison of com-monly used clinical indicators of hypovolaemia with gastric tonometry.Intensive Care Med 23:276-281, 1997Grocott MPW, Mythen MG, Gan TJ: Perioperative fluid managementand clinical outcomes in adults. Anesth Analg 100:1093-1106, 2005Heyland DK, Cook DJ, King D, et al: Maximizing oxygen delivery in

critically ill patients: a methodologic appraisal of the evidence. CritCare Med 24:517-524, 1996

30. Shoemaker WC, Appel PL, Kram HB, et al: Prospective trial of su-pranormal values of survivors as therapeutic goals in high-risk surgicalpatients. Chest 94:1176-1186, 1988

31. Berlauk JF, Abrams JH, Gilmour IJ, et al: Preoperative optimisation ofcardiovascular hemodynamics imroves outcome in peripheral vascularsurgery. A prospective, randomised clinical trial. Ann Surg 214:289-297, 1991

32. Lobo SMA, Salgado PF, Castillo VGT, et al: Effect of maximising oxygendelivery on morbidity in high-risk surgical patients. Crit Care Med28:3396-3404, 2000

33. Mythen MG, Webb A: Perioperative plasma volume expansion reducesthe incidence of gut mucosal hypoperfusion during cardiac surgery.Arch Surg 130:423-429, 1995

34. Venn R, Steele A, Richardson P, et al: Randomised controlled trial toinvestigate influence of the fluid challenge on duration of hospital stayand perioperative morbidity in patients with hip fractures. Br J Anaesth88:65-71, 2002

35. Sinclair S, James S, Singer M: Intraoperative intravascular volume op-timisation and length of hospital stay after repair of proximal femoralfracture: randomised controlled trial. BMJ 315:909-912, 1997

36. Gan TJ, Soppitt A, Maroof M, et al: Goal-directed intraoperative fluidadministration reduces length of stay after major surgery. Anesthesiol-ogy 97:820-826, 2002

37. Conway DH, Mayall R, Abdul-Latif MS, et al: Randomised controlledtrial investigating the influence of intravenous fluid titration using oe-

sophageal Doppler monitoring during bowel surgery. J Anesth57:845-849, 2002

38. Wakeling HG, McFall MR, Jenkins CS, et al: Intraoperative oesophagealDoppler guided fluid management shortens postoperative hospital stayafter major bowel surgery. Br J Anaesth 95:634-642, 2005

39. Noblett SE, Snowden C, Shenton BK, et al: Randomized clinical trialassessing the effect of Doppler-optimized fluid management on out-come after elective colorectal resection. Br J Surg 93:1069-1076, 2006

40. Abbas SM, Hill A: Systematic review of the literature for the use ofoesophageal Doppler monitor for fluid replacement in major abdomi-nal surgery. J Anesth 63:44-51, 2008

41. Giglio MT, Marucci M, Testini M, et al: Goal-directed haemodynamictherapy and gastrointestinal complications in major surgery: a meta-analysis of randomised controlled trials. Br J Anaesth 103:637-646,2009

42. NCEPOD: Report of the 1998-99 National Confidential Enquiry intoPerioperative Deaths. Then and Now. National Confidential EnquiryInto Perioperative Deaths, London, 2000

43. Kirby R: Perioperative fluid therapy and postoperative pulmonary ede-ma: cause-effect relationship? Chest 115:1224-1226, 1999

44. Powell-Tuck J, Gosling P, Lobo DN, et al: British Consensus Guidelineson intravenous fluid therapy for adult surgical patients. GIFTASUP,2010. http://www.ebpom.org/publications

45. Bellamy MC: Wet, dry or something else? Br J Anaesth 97:755-757,2006

164 S.E. Noblett and A.F. Horgan

Perioperative Fluid ManagementHistory of Perioperative Fluid ManagementHazards of a Liberal Fluid RegimenEvolution of Fluid RestrictionCurrent Perspective: Individualized Goal-Directed TherapyThe Future of Perioperative Fluid ManagementReferences