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Umeå University Medical Dissertations New series no 1632 ISSN 0346-6612 ISBN 978-91-7459-807-0
_______________________________________________ Department of Surgical and Perioperative Sciences,
Anesthesiology and Intensive Care, Umeå University, Sweden
Assessment and management of bariatric surgery patients
Tomi Pösö
Department of Surgical and Perioperative Sciences
Anesthesiology and Intensive Care, Umeå University 2014
Responsible publisher under swedish law: The Dean of the Medical faculty.
This work is protected by the Swedish Copyright Legislation (Act 1960:729)
ISBN: 978-91-7459-807-0. Copyright © 2014 Tomi Pösö.
ISSN: 0346-6612
Cover foto: Varkaankuru, Ylläs, Finland. Foto by Tomi Pösö.
Elektronisk version tillgänglig på http://umu.diva-portal.org/
Printed by: Print Media, Umeå, Sweden, 2014.
”Kaiken viisauden alku on tosiasioiden tunnustaminen.” “The beginning of all wisdom is the confession of the facts.”
J.K. Paasikivi
The president of Finland, 1946 - 1956.
This work is dedicated to my Family.
i
Table of Contents
Table of Contents i Preface iii Abstract iv List of papers v Abbreviations vi Sammanfattning på svenska/ Summary in Swedish viii Introduction 1
Epidemiology 1 Obesity – the perioperative challenge 3
Background 4 Preoperativ surgical optimization 4 Impact of obesity on physiology – an anesthesiological point of view 5 Obesity and the respiratory system 5 Obesity and the cardiovascular system 7 Pharmacological aspects and anesthetic drugs in obesity 11 Airway management, positioning, preoxygenation and perioperative
oxygenation 17 Monitoring strategies and fluid management 21 Intra-abdominal pressures and pneumoperitoneum in morbid obesity 24 Postoperative considerations in bariatric surgery 24
The aims of the thesis 26 Methods 27
Study design and etics 27 Patients and methods 27 Anesthesia and preoxygenation techiques used in this thesis 28 Echocardiography 31 Fluids 36 Inotropic and vasoactive drugs 37 Paper I 37 Paper II 37 Paper III 39 Paper IV 40 Statistics 43 Limitations 43
Results 45 Discussion 56 Conclusions 63 Future implications 64 Acknowledgements 66
Economical support 67
ii
Permissons and reprints 67 References 68
iii
Preface Every individual has right to medical care of high quality achieved by
best-practise methods regardless of age, ethnicity, race, color or body
mass index (BMI). During recent decades, patient characteristics have
changed significantly. The number of patients with overweight,
obesity and severe obesity with concomitant comorbidities has
increased substantially in anesthesia practice and intensive care. This
presents a challenge for the entire perioperative staff.
The basis for an acceptable outcome is awareness of the perioperative
concerns that may arise in patients with a high BMI. In severe obesity
uncontrolled airway or hemodynamic instability may lead rapidly to
deleterious consequences. Thus, safe, reproducible and thoroughly
implemented methods for airway control, fluid management, drug
dosing and monitoring are addressed in these individuals.
To manage these issues may be an awkward perioperative challenge,
but is definitely a part of anesthesia practice worldwide today. With
this thesis, I hope to increase knowledge and improve understanding
of the key issues in morbid obesity from an anesthesiological point of
view.
At last, I will express my motivation and source of inspiration for this
work by quoting the words of Mark Twain: “Twenty years from now
you will be more disappointed by the things you didn’t do than by the
ones you did do. So throw off the bowlines, sail away from the safe
harbor. Catch the trade winds in your sails. Explore. Dream.
Discover.”
Luleå, Sweden, the 16th of January, 2014
Tomi Pösö
iv
Abstract
Background: In morbidly obese individuals (MO) cardiorespiratory
comorbidities and body habitus challenge the perioperative management of
anesthesia. To implement safe and reproducible routines for anesthesia and
fluid therapy is the cornerstone in order to minimize anesthesia-related
complications and to meet individual variability in rehydration needs.
Methods: Paper I: Impact of rapid-weight-loss preparation prior to
bariatric surgery was investigated. Prevalence of preoperative dehydration
and cardiac function were assessed with transthoracic echocardiography
(TTE). Paper II: The anesthetic technique for rapid sequence induction
(RSI) in MO based on a combination of volatile and i.v. anesthetics was
developed. Pre- and post-induction oxygenation, blood pressure levels and
feasibility of the method was evaluated. Paper III: The preoperative ideal
body weight based rehydration regime was evaluated by TTE. Paper IV:
Need of rehydration during bariatric surgery was evaluated by comparing
conventional monitoring to a more advanced approach (i.e. preoperative
TTE and arterial pulse wave analysis). Results: Rapid-weight-loss
preparation prior to bariatric surgery may expose MO to dehydration. TTE
was shown to be a robust modality for preoperative screening of the level of
venous return, assessment of filling pressures and biventricular function of
the heart in MO. The combination of sevoflurane, propofol, alfentanil and
suxamethonium was demonstrated to be a safe method for RSI regardless of
BMI. The preoperative rehydration regime implemented by colloids 6 ml/kg
IBW was an adequate treatment to obtain euvolemia. In addition,
preoperative rehydration seems to increase hemodynamic stability during
intravenous induction of anesthesia and even intraoperatively. Conclusion:
This thesis describes a safe and comprehensive perioperative management of
morbidly obese individuals scheduled for bariatric surgery. Hemodynamic
and respiratory stability can be achieved by implementation of strict and
proven methods of anesthesia and fluid therapy. Much focus should be
placed on feasible monitoring and preoperative optimization in morbidly
obese individuals for increased perioperative safety.
Keywords: Bariatric surgery, morbid obesity, anesthesia,
echocardiography, fluid therapy, preoperative, perioperative, venous return,
rehydration, volatile rapid sequence induction, spontaneous breathing,
sevoflurane.
v
List of papers
This thesis is based on the following papers, which will be referred to in the
text by their Roman numerals:
I Poso T., Kesek D., Aroch R. and Winso O. Rapid weight loss is associated with preoperative hypovolemia in morbidly obese patients. Obes Surg. 2013 Mar; 23(3):306-13.
II Poso T., Kesek D., Winso O. and Andersson S. Volatile rapid sequence induction in morbidly obese patients. Eur J Anaesthesiol 2011 Nov; 28(11):781-7.
III Poso T., Kesek D., Aroch R. and Winso O. Morbid obesity and preoperative fluid optimizing. Obes Surg. 2013 Nov; 23(11):1799-805.
IV Poso T., Winso O., Aroch R. and Kesek D. Perioperative fluid guidance with transthoracic echocardiography and pulse-contour device in morbidly obese patients. Submitted.
vi
Abbreviations
CG, control group
CO, cardiac output
CI, cardiac index
IAP, intra-abdominal pressure
IBW, ideal body weight
LBW, lean body weight
MO, morbidly obese patients
NIBP, non-invasive blood pressure
OSAS, obstructive sleep apnoea syndrome
OHS, obesity hypoventilation syndrome
PONV, postoperative nausea and vomiting
RAP, right atrial pressure
RSI, rapid sequence induction
RYGB, Roux-en-Y gastric bypass
RWL, rapid weight loss
SAP, systolic arterial pressure
SpO2, peripheral saturation
MAP, mean arterial pressure
SV, stroke volume
ΔSV, change of stroke volume
SVV, stroke volume variation
TBW, total body weight
vii
VC, volume challenge
VR, venous return
Abbreviations for Echocardiography:
A4C, apical 4-chamber projection
A2C, apical 2-chamber projection
DD, diastolic dysfunction
EF, ejection fraction
FS, fractional shortening
IVC, inferior vena cava
IVCCI, inferior vena cava collapsibility index
LV, left ventricle
LVEDA, left ventricular end-diastolic area
LVESA, left ventricular end-systolic area
LVOT, left ventricular outflow tract
LVOTd, left ventricular outflow tract diameter
PLAX, parasternal long axis projection
PW, pulsed-wave Doppler imaging
RV, right ventricle
SAX, parasternal short axis projection
TAPSE, tricuspidal annular plane systolic excursion
TDI, tissue Doppler imaging
TTE, transthoracic echocardiography
viii
Sammanfattning på svenska/ Summary in Swedish
Bakgrund Förekomst av fetma (body mass index, BMI ≥ 30 kg/m²) och sjuklig fetma
(BMI ≥ 35 kg/m²) har ökat dramatiskt globalt. Till följd av detta har
överviktskirurgi blivit ett allt vanligare ingrepp. I Sverige har antalet
operationer ökat tiofaldigt under det senaste decenniet, och de senaste åren
har det opererats upp emot 9000 patienter nationellt. Fetma, särskilt sjuklig
fetma, anses vara en viktig faktor bakom ökad morbiditet och mortalitet i
kardiovaskulära och respiratoriska sjukdomar, hjärtsvikt, diabetes och
njursvikt. Perioperativt omhändertagande av patienter med sjuklig fetma är
utmanande på grund av ovanstående komorbiditeter samt en patologisk
kroppskonstitution. Risk för hjärt- och lungrelaterade komplikationer ökar
vid högt BMI jämfört med individer med ett normalt BMI vid operativa
ingrepp.
Några vedertagna rutiner för optimal narkos och vätskeersättning vid
överviktskirurgi finns ej i nuläget. Således, utveckling av patientsäkra
metoder för både narkos och vätsketerapi är hörnstenar för att minimera
perioperativa anestesirelaterade komplikationer i denna patientgrupp.
Syfte Syftet i avhandlingen var att utveckla en hemodynamiskt och respiratoriskt
stabil metod för induktion av anestesi i sjukligt obesa individer, och att
etablera rutiner för att erhålla normalt venöst återflöde under en
överviktskirurgisk operation.
Metoder Delarbete I: Effekter av den snabba viktminskningen inför överviktskirurgi
undersöktes. Förekomst av preoperativ vätskebrist och hjärtfunktion
bedömdes med transthorakalt hjärtultraljud (TTE). Delarbete II: En metod
för nedsövning anpassad för sjukligt överviktiga individer utvecklades. Den
undersökta tekniken för snabb nedsövning (”rapid sequence induction”, RSI)
baserades på en kombination av narkosgas och i.v. anestetika. Metodens
genomförbarhet och reproducerbarhet utvärderades bland annat genom att
följa förändringar i syresättning, arteriellt blodtryck och förhållanden för
endotrakeal intubation. Delarbete III: En metod för preoperativ rehydrering
baserad på idealvikt (IBW) utvärderades med transthorakalt hjärtultraljud
med särskild fokus på diastolisk funktion av vänster kammare. Delstudie IV:
Behov av total rehydrering i laparoskopisk överviktskirurgi utvärderades
genom att jämföra konventionell övervakning med en mer avancerad metod.
ix
Ett individualiserat protokoll för rehydrering (”individualized goal directed
therapy”) implementerades med hjälp av preoperativt transthorakalt
hjärtultraljud och intraoperativt arteriell pulsvågsanalysteknik.
Resultat Delstudie I: Brist på venöst återflöde och nedsatt diastolisk funktion i
vänster kammare var vanligare i gruppen planerad för överviktskirurgi
jämfört med i den normalviktiga kontrollgruppen. Preoperativt
transthorakalt hjärtultraljud bedömdes vara en välfungerande och snabb
modalitet för att bedöma grad av venöst återflöde och hjärtfunktion oavsett
BMI. Delstudie II: Studieprotokollets metod för preoxygenering och
nedsövning med kombination av sevofluran, propofol, alfentanil och
succamethonium var ett hemodynamiskt och respiratoriskt stabilt sätt att
genomföra en RSI induktion i både gruppen planerad för överviktskirurgi
och kontrollgruppen. Delstudie III: Preoperativ IBW-baserad
vätskeersättning var en välfungerande metod för att nå normovolemi inför
överviktskirurgi. Tillräcklig information om tryck-volym-förhållanden i
vänster kammare under pågående rehydrering kan nås redan med
konventionella Doppler index jämfört med vävnadsdoppler vid patienter
med ett högt BMI. Delstudie IV: Ökad perioperativ kardiovaskulär stabilitet
kan nås med preoperativ rehydrering. Hanteringen av vätsketerapi bör
individualiseras. Preoperativ kartläggning och optimering av venöst
återflöde kan behövas vid sjuklig fetma inför överviktskirurgi. Invasiv
perioperativ övervakning kan ge ytterligare information om hemodynamik,
men är ej avgörande inom okomplicerad överviktskirurgi. Konventionell
intraoperativ kardiovaskulär övervakning verkar vara tillräckligt för
ändamålet.
Konklusioner Perioperativ kardiovaskulär och respiratorisk stabilitet vid sjuklig fetma kan
nås genom att implementera noggranna och beprövade metoder för anestesi
och vätsketerapi. Icke- eller miniinvasiv monitorering och målstyrda
vätskeersättningsprotokoll bör nyttjas inom överviktskirurgi för perioperativ
hemodynamisk stabilitet, och för att nå optimal grad av venöst återflöde.
Stort fokus bör läggas på preoperativ optimering av cirkulation och
lungfunktion för hög patientsäkerhet vid sjuklig fetma och överviktskirurgi.
1
Introduction
Epidemiology Prevalence of obesity (body mass index, BMI ≥ 30 kg/m²) and morbid
obesity (BMI ≥ 35 kg/m²) has rapidly increased worldwide (1, 2) in recent
decades. Adult obesity in the USA has increased from 14 to 31 % in two
decades (1978 - 2000) and is still increasing. In the UK, adult obesity has
increased from 6 to 21 % in men and from 8 to 23.5 % in women in 20 years
(1980 – 2001) (3-5). Similar trends can be seen nationally. In Sweden, the
prevalence of obesity has increased in adult (25 - 64 years) men from 10.4 to
19.1 % and in women from 12.9 to 17.9 % in two decades (1986 -2004) (6).
Obesity, android distribution of excess fat in particular, is associated with
increased morbidity in several comorbidities such as cardiovascular (e.g.
heart failure, coronary disease, arrhythmias, venous thromboembolism) and
respiratory diseases (bronchial and cardiac asthma, obstructive sleep apnoea
syndrome (OSAS) and obesity hypoventilation syndrome (OHS)) in addition
to diabetes mellitus, kidney failure, gastro-oesophagal reflux, infertility,
urinary incontinence, chronic pain, fatique and many types of cancer (2, 7-
15) (Figures 1 and 2). Obesity is now considered the most common metabolic
disease in mankind (16). In adults, obesity has frequently been a long-lasting
problem (6) (I, II, III). Obesity, especially morbid obesity, is associated with
reduced life expectancy of 8 - 10 years (17). Permanent weight loss has been
reported to reduce incidence and severity of co-morbidities and the risk of
dying prematurely (18-25). In addition, significant weight loss, after e.g.
weight loss surgery, provides significant improvements in health-related
quality of life (26-30).
Weight loss surgery (bariatric surgery) has proven to be an efficient way to
decrease morbid obesity. In fact, surgery is the most important and best
evidence-based treatment option for patients with severe obesity (26, 31-36).
During the last decades the need for bariatric surgery has increased
substantially world wide. In Sweden, the number of bariatric operations has
increased approximately tenfold during the last decade; approximately
9,000 patients have been operated annually during the last two years. In
Sweden general indications for surgery are BMI ≥ 40 kg/m² or ≥ 35 kg/m²
with significant co-morbidities, regardless of gender. Furthermore, patients
must have attempted to lose weight seriously with conventional methods
before considered for surgical intervention. Several surgical techniques are
in daily use in the world, but in Sweden almost all patients undergo surgery
by laparoscopic Roux-en-Y gastric bypass technique. In Sweden, mean time
for bariatric surgery is approximately 75 minutes, length of hospital stay 2.1
2
days and 30-day mortality 0.05 % (26, 34). In general, bariatric surgery is
categorized as intermediate to high-risk non-cardiac surgery (37-39).
Prevalence of severe obesity is about as common in Swedish men as in
women. However, a majority of patients that have undergone bariatric
surgery are female. This may be due to that women are more active in
seeking, and are remitted more often for, bariatric surgery compared to men.
The majority of patients have been middle-aged adults, but also adolescents
have been accepted for bariatric surgery recently even in Sweden (34, 40).
Figure 1. Some pathophysiological consequences of obesity.
3
Figure 2. Comorbidities and pathophysiological effects associated with a long-lasting
obesity. Reproduced from O’neill T, Allam J.. Anaesthetic considerations and
management of the obese patient presenting for bariatric surgery. Current
Anaesthesia & Critical Care 2010; 21 (1): 16 – 23 by permission of Elsevier Limited
(41).
Obesity – the perioperative challenge The perioperative management of patients with a high BMI is a definitive
challenge not only for an anesthetist but for the entire perioperative staff. In
severe obesity the amount of physiological functional reserve is narrowed
due to body habitus and cardiopulmonary involvement. The hyperdynamic
circulation, increased blood volume and altered lean body mass/total body
mass ratio change pharmacological dosing principles considerably compared
to lean individuals. Airway management may be complicated due to excess
fat tissue in face and neck. In addition, appropriate positioning of severely
obese individuals for surgery is a challenge. These obesity-related problems
may increase risks of perioperative complications compared to individuals
with a normal BMI (I-IV) (15, 42-48).
4
Thus, in severe obesity, thorough preoperative risk assessment and planning
of the perioperative course is crucial. A detailed anesthetic plan must be
made by anesthetist expertise on an individual basis (II, IV) (15, 41, 45, 49).
Preoperative investigations as echocardiography, spirometry and chest X-ray
are recommended (39, 50-52) to rule out severe pathologies such as
restrictive respiratory impairment, obesity cardiomyopathy and/or cor
pulmonale. In addition, development of safe routines for anesthesia and
indepth understanding of fluid therapy for patients with a high BMI are
fundamental to minimize perioperative anesthesia-related complications (I,
II, III) (41, 45). Furthermore, a good teamwork between the experienced
surgeon and the anesthesia staff is essential for patient safety and adequate
results (IV) (33, 38).
Background
Preoperativ surgical optimization Excess epigastric and intra-abdominal fat tissue and increased size of liver
(53) complicate both laparoscopic and open gastrointestinal surgery
significantly. In order to facilitate bariatric surgery in general, reduce
surgical complications and bleeding, several preoperative weight loss
strategies with durations from two weeks to six months have been
implicated. A strict preoperative “rapid weight loss” (RWL) preparation
(duration 3 - 6 weeks) by very-low calorie-diet (VLCD) has been shown to
diminish intra-abdominal fat deposits and liver size (54-58). To achieve
optimal surgical conditions morbidly obese individuals should lose weight
radically; approximately 8 - 10 % of total body weight. However, in practical
terms, minimum 5 % weight loss is generally accepted. Nowadays this kind
of preoperative RWL-preparation is accepted as requirement for bariatric
surgery in many centres in Sweden. Even longer time with the diet has been
advocated recently (26, 34).
However, preoperative physiological consequences of this very rapid, near-
starvation-period are poorly studied. Long-time weight-loosing intervention
has been reported to improve diastolic filling pattern and to diminish over-
loading and size of the heart (59-61). In this thesis, post RWL effects on
hemodynamic parameters and venous return to the heart were studied (I).
5
Impact of obesity on physiology – an anesthesiological point of view
Obesity and the respiratory system Respiratory distress is considerable in obesity. In general, morbidly obese
individuals have two main problems - chronic arterial hypoxia and carbon
dioxide retention. Oxygenation may deteriorate already at minor distractions
such as slight cold or changing a body position (43, 62). These changes will
be aggravated substantially during anesthesia, major surgery and intensive
care (Figure 3) (45, 63-66). Weight loss has been shown to reverse a majority
of these pulmonary disturbances (21, 25, 67).
Lung volumes are reduced in obesity. The diaphragm is more cranially
located. Impairment of lung function is mostly of the restrictive type and
highly position dependent (21). A significant reduction in oxygen reserve
exists even awake due to decreased functional residual capacity (63, 68, 69).
In preoperative planning for endotracheal intubation and extubation it must
be taken into account that most severe obese individuals are not able to sleep
in the supine position. In addition, a high prevalence of obstructive sleep
apnea syndrome in addition to obesity hypoventilation syndrome (10) makes
the use of short-acting anesthetic agents necessary (II, IV) (15, 45, 47, 70,
71).
In general, the work of breathing is increased in obesity (63, 72). Both extra-
and intra-thoracic factors are associated with increased respiratory
resistance. Extra-thoracic factors are more evident particularly in abdominal
and thoracic obesity. However, all morbidly obese individuals suffer more or
less of increased airway resistance due to propensity for chronic
hypervolemia, volume and pressure strain in the heart and a high venous
pressure in the pulmonary circulation. This can be noticed for example as a
high prevanlence of orthopnea associated with morbid obesity - a clear sign
of high filling pressures and decreased compliance of the left ventricle (I)
(45, 73, 74) (Figures 5 and 6).
6
Figure 3. Schematic representation of the effects of severe obesity on functional residual capacity (FRC). Reproduced from Adams J.P. and Murphy P.G. Obesity in anesthesia and intensive care. Br J Anaesth 2000 85 (1): 91 by permission of Oxford university press (45).
During major surgery, with or without pneumoperitoneum, high airway
pressures may become problematic regardless of adequate respirator
settings, anesthesia and neuromuscular blockade. This is often a major
problem in gynecological/urogenital surgery where head-down position is
needed frequently. In bariatric surgery, this may be a concern during supine
positioning in particular (75). However, in clinical practice, during deep
reverse Trendelendburg positioning and with optimimal respirator settings,
these problems have been rare (76).
A supine position should always be avoided in morbidly obese individuals
due to an obvious risk of desaturation. Thus, a semi-sitting position is crucial
preoperatively and during the early postoperative period to avoid
desaturation related complications such as problems with CNS alertness,
wound oxygenation and healing, PONV, myocardial ischemia and arrythmias
(43, 77).
In addition, in morbid obesity, an incipient right ventricular failure may exist
due to propensity for stressed pulmonary circulation in general, chronic
arterial hypoxia and high central venous pressure. Thus, use of positive
pressure ventilation during surgery may lead to significant right ventricular
failure and, hence, jeopardize the cardiovascular stability (45, 60, 75, 78).
7
These pathophysiologic, obesity related issues are challenging to control by
anesthetists and culminate at the induction of anesthesia where carelessness
can easily lead to desaturation and hypoxia. Further, as a worst case
scenario, ischemic arrhythmias and asystole may occur (Figure 7). These
issues are explored in this thesis (I - IV).
Obesity and the cardiovascular system The cardiovascular system is strained by obesity. Biventricular hypervolemic
and hyperdynamic circulation with elevated filling pressures in the left and
right ventricles are typical in morbid obesity. The increased blood volume
usually leads to clinical consequences (45, 60, 74). Moreover, recent data
indicate that diabetes mellitus, insulin resistance and sleep disordered
breathing in obesity (e.g. OSAS, OHS) are associated with cardiovascular
remodeling and ventricular diastolic dysfunction, that is, decreased
compliance of the heart (steeper pressure-volume curve) (45, 79, 80). The
most obvious pathophysiological changes can be seen in individuals with
long-term obesity. Prolonged duration of morbid obesity (over 10 to 15
years) is strongly associated with increased left ventricular (LV) mass, left
atrial (LA) enlargement, LV diastolic dysfunction and slight to severe systolic
failure of LV (13, 45, 73, 81-83). Decreased compliance of the left ventricle
complicates the management of perioperative fluid therapy (78, 84). In
practice, both hyperhydration and deficient replacement of fluids may occur
(85).
In obesity increased total body weight consists of both increased lean body
mass (fat free body mass) and adipose tissue (Figure 8) (86). Both fat free
and adipose tissues are metabolically active and, hence, the more it exists the
more the intravascular blood volume is needed for adequate oxygen delivery.
Increased circulating blood volume, stroke volume and cardiac output (87)
are developed in response to increased metabolic demands. As a result
volume and pressure overloading of both chambers of the heart occurs (45,
81). This in turn leads to hypertrophy of the left ventricle (concentric
hypertrophy), increased left ventricular mass and increased filling pressures.
In this phase the systolic function of the left ventricle is usually preserved,
but the diastolic function of the left ventricle is clearly impaired. It should be
underlined that the majority of morbidly obese individuals scheduled for
bariatric surgery are operated at this phase (II-III). However, recent data
indicate that comprehensive utilization of tissue Doppler imaging (TDI) can
reveal signs of reduced systolic function at early obesity (88). In addition,
many of these individuals meet formal criteria for diastolic heart failure (89-
91).
8
With continued strain on circulation, obesity-related heart failure may
develope to "Obesity cardiomyopathy" which is considered to be the final
stage of this type of heart failure (81). This process can take over 20 years
(13) (Figure 4). Now, in addition to severe reduction in diastolic function, a
clear systolic left ventricular failure can be seen. The left ventricle is dilated
(eccentric hypertrophy). Reduced stroke volumes and ejection fractions can
be measured as signs of left forward failure. In addition, the critical
involvement of the right ventricle can often be diagnostized. This can be seen
as a dilated right ventricle with signs of secondary pulmonary hypertension,
relaxation disturbance and impaired systolic function (45) (Figure 5).
Figure 4. The proposed progression of structural remodeling of the left ventricle (LV)
with increasing duration and severity of obesity. In this short-axis view of the LV, the
outer circle represents the epicardium and the inner circle the endocardium. A,
Normal LV with normal LV mass and relative wall thickness. B, Increased LV
concentric remodeling (increased relative wall thickness) without frank LV
hypertrophy. C, LV concentric hypertrophy with increased relative wall thickness. D,
LV eccentric hypertrophy (increased LV mass with decreased relative wall thickness).
Reproducted and adapted from Linda R. Peterson. Obesity and Insulin Resistance:
Effects on Cardiac Structure, Function, and Substrate Metabolism. Current
Hypertension Reports 2006, 8:451–456 by permission of Springer and the author
(13).
9
Figure 5. The aetiology of obesity cardiomyopathy and its association with right‐sided heart failure, systemic hypertension and ischaemic heart disease. Reproduced from Adams J.P. and Murphy P.G. Obesity in anesthesia and intensive care. Br J Anaesth 2000; 85 (1): 91 by permission of Oxford university press (45).
At present, it is unclear whether the above mentioned pathological changes
are reversible with radical weight loss. However, it has been suggested that
the final stage of obesity-related heart failure with the restrictive diastolic
filling pattern and myocardial fibrosis is irreversible (13, 73, 82). Notably,
diet probably plays an important role in the development of fibrosis. Free
fatty acids (FFA) have been shown to cause a lipotoxic cascade in human
heart, to be a trigger for intracellular apoptosis in the myocardium via
reactive oxygen species and thus increase the risk of permanent fibrosis and
cardiomyopathy (82).
Vascular dysfunction in general and conduction pathway failure of the heart
may develop with prolonged obesity (92). In addition, the sympathetic
nervous system is overactive in individuals with a high BMI. These features
together with reduced compliance of the left ventricle are assumed to be
10
reasons for propensity for substantial changes in stroke volume and
increased tendency for arrhythmias and bradycardia during rapid changes of
body positioning. This may be a concern during laparoscopic surgery in
particular (43, 45, 49, 73, 93).
Figure 6. Top, Schematic diagram of mitral inflow and mitral medial annulus
velocities from normal to progressive stages of diastolic dysfunction. Mitral inflow E
is sensitive to preload, becoming higher with shorter deceleration time (time from the
peak to the baseline) as diastolic function becomes worse with increasing filling
pressure. However, E′ is less sensitive to preload and reduced in all stages of diastolic
dysfunction. In fact, reduced E′ is usually the earliest manifestation of diastolic
dysfunction.
Bottom, Schematic diagram illustrating “pulling” or “sucking” of blood into the LV
from LA by good relaxation in subjects with normal diastolic function (left), and
“pushing” of blood into the LV by increased filling pressure in patients with abnormal
relaxation due to severe diastolic dysfunction (right). A indicates late diastolic mitral
flow due to atrial contraction; A′, late diastolic mitral annulus velocity; E, early
diastolic velocity; E′, mitral annulus early diastolic velocity; LA, left atrium; LV, left
ventricle. Reproduced and adapted from Oh, J.K. et al. Established and novel
clinical applications of diastolic function assessment by echocardiography. Circ
Cardiovasc Imaging. 2011; 4:444-455 by permission of Wolters Kluwer Health (84).
11
Knowledge and identification of these pathophysiological obesity-related
changes in the heart is useful for the anesthetist. In these high-risk patients,
assessment of pressure-volume relationship of the left ventricle should be
performed prior to anesthesia and surgery to enable a tailored strategy for
rehydration and invasive support for circulation. Consequently, a
preoperative assessment of diastolic properties in addition to systolic
function of the heart is addressed (15, 38, 51, 78, 84) (Figure 6). These issues
were in the focus in this thesis (I, III, IV).
Pharmacological aspects and anesthetic drugs in obesity The pharmacokinetics and pharmacodynamics of many anesthetic agents are
altered in morbid obesity compared to individuals with normal weight. The
pharmacokinetics for most anaesthetic drugs follows a three compartmental
model (i.e. bolus to central compartment, elimination and transfer to
tissues) (47, 94). Both dose and time course of drugs (onset and decline) are
markedly altered due to the increased fat mass, total blood volume,
increased cardiac output and changes in regional blood flow. The volume of
distribution (V(d)) is increased for drugs that are distributed both in lean
and fat tissues. Clearance for anesthetic drugs is usually increased or normal
(94). In obesity, renal clearance is increased due to increased blood volume,
size of kidney and glomerular filtration rate (47, 95). Hepatic clearance is
usually normal or increased despite of propensity for fatty degeneration and
fibrosis of the liver (47, 93, 96).
In morbidly obese subjects an adequate choice and administration of
anesthetic drugs are fundamental for patient safety and effective care.
Incorrect administration of anesthetics (both dosing and timing) may lead to
perioperative complications such as hemodynamic collapse, intraoperative
awareness, airway management problems and postoperative drowsiness (94,
97) (II, IV). Figure 7 illustrates potential difficulties during induction of
anesthesia related to drug dosing.
12
Figure 7. The illustration of the significance of appropriate dosing in morbidly obese patients (II).
The basis for successful dosing of drugs in obesity is knowledge of total body
weight (TBW) and assessement of a fat-free body mass (i.e. lean body weight,
LBW). In general, drug dosing is usually based on TBW. This is a safe
approach for lean individuals due to similarity between TBW, LBW and ideal
body weight (IBW). However, in morbid obesity, anesthetic dosing based on
TBW may lead to overdosing and a prolonged effect. In obese population, in
addition to increased fat mass LBW also increases but not in the same
proportion (i.e. LBW / TBW ratio decreases) (Figure 8). Most of the cardiac
output still perfuses lean tissue groups because of generally low perfusion of
and low water content in excess adipose tissue. Thus, utilizing LBW for
dosing of many anesthetic drugs may be the most appropriate approach (47,
86, 94).
13
Figure 8. Relationship of TBW, fat weight, and LBW to BMI in a standard height
male. Reproduced from Ingrande J. and Lemmens H J M. Br. J. Anaesth. 2010; 105:i16-i23 by the permission of Oxford university press (86).
There are several methods for assessment of the fat-free body mass. Body
composition can be assessed both directly (e.g. by bioelectrical impedance
analysis and dual-energy x-ray absorptiometry) and indirectly. Direct
methods are not available for the majority of clinics. Consequently, many
indirect measures have been utilized (BMI, body surface area, IBW, percent
IBW, LBW). Whatever the modality is implemented, it is crucial to apply an
estimation of fat-free body mass in clinical praxis in order to avoid incorrect
dosing (Figure 7). The simple “IBW-equation” (height in cm – 100) used in
this thesis is easy to implement in practice, and gives a good approximation
of a fat-free mass of the body in morbid obesity equivalent to a BMI level
about 24 kg/m2 (II, III, IV) (45, 71). This IBW corresponds in principle to
LBW that can be obtained by direct body impedance measurements or
calculated using the generally recommended, but rather complicated
equation (98):
LBW (male) = 9.27 x 103 x TBW/6.68 x 103 + 216 x BMI
LBW (female) = 9.27 x 103 x TBW/ 8.78 x 103 + 244 x BMI.
14
Thus, the "IBW concept” used in this thesis can be interpreted as an
estimation of LBW in morbidly obese individuals.
In addition to the “right” dose per se, an appropriate speed of drug
administration is essential. Too low speed of administration may lead to
overdosing and undesired sub-clinical effects (II) (94, 99) (Figure 7). The
LBW has been shown to correlate strongly with cardiac output (87, 99).
Increased LBW leads to hyperdynamic and hypervolemic circulation
(discussed in the chapter “Obesity and the cardiovascular system”). These
features of circulation increase the speed of the drug wash-in and wash-out
times in the brain and other high-perfusion tissues. As a consequence, a fast
onset of the drug can be expected (depression of respiratory drive and
sympathetic nervous system). On the other hand, risk of undesired patient
intraoperative awareness associated with induction of anesthesia is
increased.
So, the following issues are critical for successful implementation of
induction and maintenance of anesthesia in morbidly obese individuals:
i) a knowledge of total body weight (TBW),
ii) an estimation of fat-free body weight (LBW, IBW),
iii) a calculation of a theoretical appropriate dose for anesthetics
and
iv) an appropriate speed and timing of drug administration.
Nevertheless, despite of preoperative calculation of drug doses an anesthetist
should always be alert to adapt management according to clinical responses
and have inotropic and vasoactive drugs immediately available (IV).
Anesthetics, opiates and neuromuscular blockers Volatile anesthetics: As discussed above, administration of most anesthetic
drugs is altered in mordbily obese individuals compared to lean subjects.
However, the uptake of volatile anesthetics (e.g. isoflurane, sevoflurane, and
desflurane) is not significantly changed in morbid obesity. A low blood/gas
distribution coefficient and low lipid solubility are obligate for rapid
induction and recovery. In morbid obesity, the drugs of choice at the
moment are sevoflurane and desflurane (II, IV) (71, 93, 97, 100, 101). In
general, volatile anesthetics cause only a slight depression of respiratory
drive – desflurane and sevoflurane being least depressive (102, 103).
Theoretically, nitrous oxide could be an optimal choice in morbid obesity
15
because of its analgesic properties and fast recovery but propensity to high
oxygen demand during surgery and increased risk of PONV limits its use.
In current times, a volatile anesthetic induction can best be implemented
with sevoflurane. Desflurane causes respiratory irritation, and therefore is
not recommended as an induction agent. Sevoflurane can be used as an
induction agent with various techiques (e.g. tidal volume, single-breath and
vital capacity techniques) (II) (104, 105) for children, difficult airway, risk of
desaturation and emergency surgery. Moreover, sevoflurane induction is
associated with less hemodynamic perturbation compared to propofol (106).
A lower MAC-value (~0.8) in combination with short acting opiates is
generally recommended in bariatric surgery today (71, 97, 107) (II, IV). In
addition, volatile anesthetics can be monitored reliably in all modern
anesthetic workstations (with end tidal % and MAC-concept) in contrast to
i.v. anesthetics. Moreover, postoperative reduction in lung function has
shown to be more prominent after total intravenous anesthesia compared to
conventional general anesthesia with sevoflurane (108). Thus, use of
inhalation anesthetics may be motivated in morbidly obese patients in
particular.
Hypotics: Propofol is the most commonly used i.v. hypnotic drug for both
induction and maintenance of general anesthesia even in bariatric surgery.
Propofol is a highly lipid-soluble drug with high clearance. V(d) for propofol
and clearance are propotional to TBW. The terminal elimination half-life of
propofol is not altered in obesity compared to lean individuals (47, 94). With
propofol, there is a delay between effective blood concentration and effective
site (brain) concentration that must be taken into account during anesthesia
induction. Propofol has favorable properties for induction in general. It
provides good relaxation of larynx and pharynx (109). On the other hand, in
morbidly obese subjects, this may be problematic during sedation and/or
fiberscopic awake intubation where preserved pharynx tonus (i.e. free
airway) and spontaneous breathing is desirable (110). In addition, a rapid
injection of propofol needed in morbid obesity leads to early apnoea (86).
In the morbidly obese population a rapid sequence induction of anesthesia
(RSI) is generally recommended (41, 45, 111). For the purpose, propofol is
traditionally administered with TBW as a guideline. However, in clinical
practise, a TBW-based dosing regime for induction of anesthesia results in
high doses and rapid loss of consciousness, but usually inducts a significant
decrease in blood pressure (99, 106, 112). Thus, LBW or its surrogates may
function as more appropriate weight-based scalars for induction in severe
obesity (II, IV) (71, 86, 99). However, at the moment, there is no clear
16
consensus for dosing scalar for induction dose of propofol in morbid obesity.
The use of propofol in maintenance of general anesthesia may appear less
suitable compared to volatile anesthetics. Larger doses needed during
surgery may compromise hemodynamic stability in addition to costs of the
drug (47, 71). Moreover, volatile anesthetics are clearly superior to propofol
regarding the intraoperative monitoring of dosing.
Propofol may be used as a component in total intravenous anesthesia (TIVA)
with or without target-controlled infusion systems (TCI). In morbid obesity,
calculation of mathematic compartment algorithms needed for TCI-dosing is
challenging due to altered LBW/TBW ratios (Figure 8), V(d) and
hyperdynamic circulation (Figure 5) (97). However, recent data indicates
that use of TCI systems may lead to increased hemodynamic stability and
rapid recovery even in morbid obesity. An estimation of fat-free body weight
(i.e. LBW) should be used for TCI induction and/or maintenance in bariatric
surgery (the Schnider model) (71, 86, 113). However, the TCI concept was
not used in this work, and a comprehensive review of the issue is beyond the
scope of the thesis.
Other hypnotics, such as thiopental sodium or benzodiazepines, are not
recommended for induction due to significantly increased volume of
distribution and elimination half-life (47).
Opiates: Similar to hypnotics, short acting opiate drugs are used. Alfentanil
may be the most suitable opiate for RSI-induction. This drug has a fast onset
and recovery, no respiratory adverse effects in addition to the possibility for
i.v. bolus administration (II) (114, 115). Optimal dose estimation should be
based on lean body mass (45, 47, 86). Use of remifentanil is well
documented in bariatric surgery. This drug is considered the most suitable of
all opiates for maintenance of general anesthesia in morbid obesity (71, 107).
However, propensity for muscle rigidity may limit its use as an induction
drug in morbid obesity (115). Remifentanil is highly lipophilic but, on the
other hand, is metabolized rapidly by unspecific esterases in both central and
extracellurar compartments. So, absolute volume of distribution of
remifentanil is not significantly altered compared to lean subjects, and
dosing should be based on ideal body weight (47, 71, 86, 93). After prolonged
infusion of this drug, no accumulation occurs, and no risk of postoperative
sedation and/or respiratory depression exists in addition to low incidence of
PONV (116). However, according to recent data, ultra short acting
advantages of remifentanil may not be superior to other opiates (e.g.
sufentanil) if perioperative administration is implemented by TCI-systems
(117).
17
Neuromuscular blocking drugs: Increased dose of depolarising agents
(suxamethonium) is needed due to increased blood volume and
pseudocholinesterase activity. Dosing scalars by total body weight has been
proposed (45, 47, 118). However 120 - 150 mg (i.e. 0.7 - 0.8 mg/kg TBW)
seems to be a most appropriate dose (II). Furthermore, use of
suxamethonium together with opioids and hypnotics have been shown to
have less undesirable effects on direct laryngoscopy circumtances compared
to non-depolarising neuromuscular blocking drugs (II) (111).
Use of total body weight for dosing of non-depolarisizing neuromuscular
blocking agents will result in a prolonged effect. Thus, the LBW or IBW is
suggested to be most appropriate for dosing of these drugs in morbid obesity
(47, 93).
Airway management, positioning, preoxygenation and perioperative oxygenation Morbid obesity is associated with increased risk for gastric aspiration
because of increased intra-abdominal pressure, gastric juice volume,
incidence of gastro-oesophageal reflux, low gastric pH and a low barrier
pressure (15, 45, 119, 120). In addition, gastric emptying may be slowed due
to high prevalence of diabetes mellitus and possible autonomic dysfuction
(i.e. gastroparesis). Hence, for these reasons, a rapid sequence induction or
awake fiberoptic technique for endotracheal intubation has been
recommended (45, 111).
There are three ways to obtain airway access in morbidly obese individuals:
i) RSI without mask ventilation, ii) induction with mask ventilation or, iii)
awake intubation. For all of these, a thorough preoperative assessment of
possible airway problems must be carried out by an experienced anesthetist.
Neck circumference and extension, the Mallampati score, mouth opening,
tendency for airway obstruction (“snoring”) while awake (e.g. in severe
OSAS) and signs of OSAS (e.g. drowsiness) should be assessed (10, 15, 45,
121, 122) (II). The inspiratory provocation test (a rapid forced inspiration,
“FIV1”) may also give additional information of a possible severe airway
obstruction.
Proper positioning is fundamental for all morbidly obese individuals – most
important is head and shoulder positions prior to preoxygenation and
induction (15, 123, 124). A “ramp” position (Figure 9) can be created with
large pillows or blankets under the shoulder in addition to tilting the head
part of the operation table (43), or with a “ramp” intubation device (“the
AirPal RAMP®, i.e. The Rapid Airway Management Positioner). This
position has been shown to facilitate circumtances for both mask ventilation
18
and direct laryngoscopy (DL), and is superior to a “sniffing” position (125).
Moreover, a “sniffing” position may be challenging to achieve because of a
heavy head-and neck region in severe obesity. Furthermore, reverse
Trendelendburg positioning (a 15 - 30 degree tilt of the table) in addition to a
“ramp” position is recommended to facilitate preoxygenation and optimize a
position of the diaphragm and the functional residual capasity (41, 126, 127).
However, a head-up position (a reverse Trendelendburg position) may
compromise venous return to the heart which may be worsened in
hypovolemia (II, IV) (43).
There are various protocols published on preoxygenation in morbidly obese
individuals. The general aim of preoxygenation is to obtain enough time for
endotracheal intubation without a risk of desaturation. This can be achieved
by preoperative lung recruitment (i.e. applying continuous positive airway
pressure aiming to diminish atelectasis and shunting and increase FRC), and
by nitrogen washout using a high fresh inflow of oxygen. The peer-reviewed
methods available vary e.g. in FiO2 applied (from 0.6 – 1.0), duration and
use and level of continuous positive airway pressure (CPAP), pressure
support and positive end-exipiratory pressure (PEEP) (i.e. non-invasive
ventilation, NIV) (II, IV) (46, 128-130). In addition, use of PEEP may
decrease the risk of regurgitation (120). In any case the most crucial
monitoring is end-tidal oxygen fraction (etFiO2), which should reach levels
at least > 0.65. It is important to notice that extreme levels of etFiO2 may
decrease the safety time for apnoea due to atelectasis formation (i.e.
absorbtion atelectasis) (131, 132).
The BMI per se is a poor predictor of difficulties in anesthetic performance.
More predictive is distribution of fat in face and around the neck and in the
upper body region (45). In these individuals airway management (difficult
mask ventilation (DMV) and endotracheal intubation) may be complicated
in particular. Already a BMI > 26 kg/m2 has been considered as an
independent risk factor for DMV (44). Hence, challenging mask ventilation
should be taken into account in most morbidly obese individuals. Problems
with DMV may be managed by implementing a rapid sequence induction
without mask-bag ventilation (II, IV) or by a four-handed technique for the
mask and the bag (15). Alternatively, respirator-assisted mask ventilation,
LMA or a nasopharyngeal tube can be placed for ventilation prior to
endotracheal intubation (133, 134).
However, endotracheal intubation is often successful in a proper positioning
(a “ramp” position) by conventional direct laryngoscopy with a short handle,
a long Macintosh blade and a stiff stylett. Under these conditions, DL
circumstances can be classified as Cormack-Lehane I/IV up to 75 % of
19
morbidly obese subjects (122). However, newer video-assissted techniques
has shown to be superior to conventional DL regarding visualization of the
larynx and success rate for endotracheal intubation but are more time
consuming (135) and, hence, increase the risk of desaturation.
Awake fiberoptic intubation is a challenge per se in patients with a high BMI.
It should be implemented only after comprehensive assessment of airways
and/or in hyper morbidly obese individuals with abdominal, face and neck
obesity with intolerance to lie in a supine position. Two operation tables may
be needed to tolerate high body masses of these patients (43). However, in
general, most patients are anesthetized and endotracheally intubated on the
operating table (II, IV) (15). This practise has a key advantage: use of a table
with appropriate weight limits (in this thesis ≤ 200 kg) a rapid in-need re-
postitioning of morbidly obese individuals is facilitated.
After endotracheal intubation a rapid systematic collapse of alveoli, or
atelectasis, occurs in morbidly obese patients. A lung recruitment maneuver
and PEEP 8 - 10 cmH2O is advocated to keep the lungs open (II, IV) (66,
136). Despite moderate levels of PEEP high supply of oxygen is generally
needed during bariatric surgery.
20
Figure 9. A proper positioning (a “ramp” position) of a morbidly obese individual in
order to facilitate mask-bag ventilation, oxygenation and endotracheal intubation.
Reproduced from Brodsky J.B. Positioning the Morbidly Obese Patient for
Anesthesia. Obesity Surgery 2002 Dec; 12(6): 751-758 by the permission of Springer
(43).
Conclusively, the cornerstones for a safe induction of anesthesia and
sufficient oxygenation during surgery are:
i) preoperative optimizing and medical treatment of respiratory
and cardiac comorbidities,
ii) proper positioning (a “ramp” position) during preoxygenation,
iii) adequate FiO2 and sufficient duration of preoxygenation,
iv) use of vital capacity breathing, CPAP and/or NIV during
preoxygenation,
v) intraoperative recruitment of lungs and use of PEEP,
vi) monitoring of end-tidal FiO2 levels and intrinsic PEEP,
vii) adjusting levels of I:E ratio, frequence and respirator mode
when necessary.
21
Monitoring strategies and fluid management In general, regardless of BMI, rapid treatment of hypovolemia is obligatory
to re-establish and sustain blood pressure, blood flow and adequate tissue
and renal perfusion. On the other hand, hyper-hydration of fluids may lead
to tissue edema and impaired oxygenation and organ dysfunction. This may
have clinical manifestations which include pulmonary strain with urgent
need for non-invasive ventilatory support, increased risk of postoperative
wound infections and prolonged length of hospital stay (85, 137, 138).
In severe obesity, perioperative fluid administration is a particular challenge
because of propensity for heart failure, reduced compliance of the heart,
vasomotoric dysfunction, respiratory strain and varying lean body mass (41,
45, 75). There is no clear consensus for fluid therapy in bariatric surgery at
the moment. Published fluid replacement recommendations vary from
liberal to restrictive approaches (III, IV) (41, 85, 93, 139). Assessment of
rehydration needs is additionally complicated by non-standardized routines
for preoperative weight loss preparation with a potential impact on venous
return and hydration balance (I, III, IV) (55-58). In order to manage these
challenges functional non- or mini-invasive modalities for cardiovascular
monitoring and lean/ideal body weight estimates are addressed to meet
individual variability in rehydration needs (III, IV) (85, 93, 137, 138, 140-
142).
At the moment, individualized goal-directed volume therapies (IGDT), based
on functional hemodynamic parameters, are generally recommended for
monitoring hemodynamics and fluid therapy. Conventional, “static”,
pressure-based monitoring (mean arterial pressure (MAP), central venous
pressure (CVP) or pulmonary capillary wedge pressure (PCWP)) have not
been shown to decrease perioperative morbidity and mortality in major
surgery (137, 138, 143).
The choice of monitoring may depend on availability and user knowledge.
There are several commercially available modalities that produce dynamic,
flow-based on-line data; e.g. FloTrac™, LiDCO™, ccNexfin™, PICCO™,
Cardio Q™ and echocardiography. It is a challenge to choose the most
suitable monitoring system in terms of patient population, body habitus,
clinical situation and type of surgery. Several different modalities can and
should be used concomitantly. Obtained information should then be merged
together to achieve the best results (Figure 10) (IV) (142, 144, 145).
22
Figure 10. The illustration of integrative concept for the use of cardiac output
monitoring devices. Abbreviations: ED, emergency department; HD, hemodynamic;
ICU, intensive care unit; OR, operating room; PAC, pulmonary artery catheter.
Reproduced from Alhashemi J. A. et al. Critical Care 2011, 15:214 by the permission
of Springer (144).
There are several dynamic parameters available to assess need of
rehydration and preload responsiveness. At the moment best documented
parameters are stroke volume variation (SVV), systolic pressure variation
(SPV), pulse pressure variation (PPV), inferior or superior vena cava
collapsibility index (IVCCI and SVCCI, respectively) (137, 143-151).
In general, goal-directed protocols are usually designed to maximize stroke
volume by administration of i.v. fluids, use of intropic and/or vasoactive
medication aiming to increase oxygen delivery (137, 138). These protocols
can be implemented preoperatively, intraoperatively and postopertively (e.g.
at ICU or recovery unit). The intraoperative approach is most often applied
23
because of the nature of validation studies and monitoring limitations during
spontaneous breathing. However, the importance of pre-optimization (i.e.
preoperative) protocols has been raised recently, but evidence for these is
still sparse (I, III, IV) (137, 152). For this purpose, in fact, transthoracic
echocardiography is the only modality reliable and robust enough to be used
in subjects with spontaneous breathing (78, 153, 154). To my knowledge, the
papers in this thesis are the first published studies in morbidly obese
individuals in this context (I, III, IV).
Mini-invasive pulse-contour device FloTrac
The mini-invasive FloTrac™ device (version 3.01, Edwards Life sciences,
Irvine, CA, USA) was used in paper IV only. The accuracy and reliability of
the device is comprehensively validated (153, 155-159) even in laparoscopic
surgery and obesity (160, 161). The device can be utilized as continuous
monitoring for all kinds of surgery, but only during controlled ventilation.
An arterial line is needed for measurements and analyse. The FloTrac
produces continuous data on stroke volume, stroke volume variation, cardiac
output, and can be extended to cover measurements of systemic vascular
resistance and central venous saturation (ScVO2) with a central venous line
when necessary. Potential source of inaccuracies are spontaneous breathing,
arrhythmias and other non-sinus rhythms as nodal rhythm and reduced
thorax wall compliance (137). The FloTrac algorithm calculates stroke
volume every 20 seconds by using arterial pressure, age, gender and body
surface area in the general equation SV = K x pulsatility. Body surface area is
calculated by the Dubois formula. In the 3rd generation software the
conversion factor Khi (K) accounting for arterial compliance is updated every
60 seconds automatically, and manual calibration is not required. Thus, the
data should be registered minimum one minute from actions that might
influence arterial compliance (e.g. administration of vasodilating i.v. drugs
or a major change of position) (162, 163). A more detailed description of the
technique applied in the FloTrac is beyond the scope of this thesis (137, 155).
24
Intra-abdominal pressures and pneumoperitoneum in morbid obesity Increased intra-abdominal pressure (IAP) levels have been reported in
morbidly obese subjects (164, 165). According to the recent consensus
statement established by the World Society of the Abdominal Compartment
Syndrome (WSACH) and the expert group (166) intra-abdominal pressure
levels are graded as follows: i) Grade I, IAP 12–15 mmHg, ii) Grade II, IAP
16–20 mmHg, iii) Grade III, IAP 21–25 mmHg i.e. abdominal compartment
syndrome, and iv) Grade IV, IAP > 25 mmHg.
Abnormal IAPs may have an impact on inferior vena cava and venous return
to the heart. Hemodynamic effects of pneumoperitoneum depend on the
degree of intra-abdominal pressure and the hydration balance of a patient.
In euvolemic subjects, during a slight pneumoperitoneum (IAP < 10-15
mmHg) a thoracic compartment gain occurs (splanchnic blood recruitment)
and, hence, venous return increases. In hypovolemia, this response is absent.
A high IAP (> 15 - 20 mmHg) may compromise venous return and
hemodynamic stability even in euvolemia, as well as decrease perfusion in
the splanchnic region, and impair renal and lung function (93, 164-167).
Consequently, it is crucial to endeavor for IAP-levels < 15 mmHg and
euvolemia during laparoscopic bariatric surgery. Euvolemia/optimal filling
pressures of the heart should be reached before induction of anaesthesia and
maintained at this level perioperatively to guarantee a sufficient coronary
flow and organ perfusion in addition to avoid excessive/theoretical
activation of the renin-aldosterone-angiotensin system (RAAS) (75). Thus, in
general, functional hemodynamic monitoring for fluid therapy and IAP is
recommended for subjects with increased IAP (166) (IV).
Postoperative considerations in bariatric surgery The early postoperative care is critical in bariatric surgery. Rigorous
monitoring of oxygenation and respiratory rate, renal function and signs of
tachycardia (as a sign of anastomotic leakage and bleeding) and cardiac
failure must be conducted. A standardized, but still individualized,
postoperative care is addressed with focus on: i) careful fluid therapy ii)
good pain control, iii) to minimize use of opioids and other sedative drugs,
iv) to minimize risk of post-operative nausea and vomiting, v) to optimize
patient positioning to ensure good cardiorespiratory function and, vi) early
mobilization (97) (IV).
In general, postoperative lung function (both lung volumes and dynamic
function) is significantly reduced after surgery and general anesthesia in
morbid obesity (45, 65, 77). Prolonged invasive respirator therapy must be
25
avoided whenever possible and, hence, a morbidly obese patient should be
extubated fully awake in the sitting/semi-sitting position as early as possible.
A CPAP-apparatus intended for the care of OSAS must be at hand in the
postoperative care unit (93). In risk assessment it should be taken into
account that reported prevalence of OSAS/OHS is misleading and most
morbidly obese individuals may have subclinical and undiagnosed OSAS or
even OHS. Thus, implementing postoperative CPAP therapy must be
considered if signs of airway obstruction are detected (10). Even a scheduled
CPAP therapy for all morbidly obese patients has been advocated. The
postoperative use of NIV and/or CPAP has been shown to be a safe approach
for increasing oxygenation in bariatric surgery without increased risk for
aspiration or anastomotic leakage (41, 93).
In association with these studies, a postoperative program with an overnight
observation at the postoperative recovery unit is implemented. A head-up
position is obligate in addition to intermittent positive pressure breathing.
CPAP can be applied when necessary. The triple antiemetic prophylaxis (71,
168) (ondanzetron 4 mg, betamethasone 8 mg and dihydrobenzoperidol 0.75
mg) is given intravenously to all morbidly obese individuals. Postoperative
pain control is initiated with preoperative paracetamol, intraoperative i.v
non-steroidal anti-inflammatory drug (NSAID) (diclofenac 75 mg) and i.v.
morphine 0.1 mg/kg IBW (injected 20 minutes before extubation). In
addition to these drugs, intraperitoneal local anesthesia is administrated by
the surgeon. In case of open and/or converted surgery two epidural catheters
are placed in the wound bilaterally. In these catheters intermittent injections
of bupivacaine may be administered. When necessary, intermittent
administration of clonidine may be considered. Alternatively, if anatomic
circumstances and body habitus are favorable, continuous epidural analgesia
is conducted. Transversus abdominis plane (TAP) blocks (169) are not
routinely used in these patients in our clinic.
26
The aims of the thesis
The primary aims of the thesis are:
i) to assess the prevalence of dehydration (hypovolemia) before bariatric surgery using transthoracic echocardiography (Paper I),
ii) to validate a cardiorespiratory stable combination of anesthetics to perform a controlled induction of anesthesia ("rapid sequence induction") suitable for morbidly obese individuals (Paper II),
iii) to evaluate a preoperative rehydration regime by a comprehensive protocol for transthoracic echocardiography with focus on venous return to the heart, volume responsivness and diastolic function of the left ventricle (Paper III),
iv) to evaluate need of rehydration during laparoscopic bariatric surgery using transthoracic echocardiography and an arterial pulse wave analysis technique (Paper IV).
27
Methods
Study design and etics Data collection took place between October 2009 and November 2013 in
Sunderby county hospital, Luleå, Sweden. Studies I and II were consecutive,
controlled, non-randomized, prospective observation studies. The design of
study III was controlled (cross-over), consecutive, propective and
interventional. Study IV was a consequtive, controlled, non-randomized,
prospective interventional study. Ethical approvals (DNR 09-042M, DNR
2010-287-32M and DNR 2012-439-32M) by the Regional Ethical Review
Board, Umeå, Sweden, were obtained for all substudies. In addition, studies
III and IV were registered at the ClinicalTrials.gov database.
Patients and methods The morbidly obese subjects studied (n = 132, mean BMI 42.2 kg/m2, (36 -
56.7) were scheduled for bariatric surgery by laparoscopic Roux-en-Y gastric
bypass (RYGB) and were prepared by 3 weeks rapid-weight-loss diet (RWL)
before bariatric surgery. In addition, these subjects fasted six hours before
surgery (a nil-per-os period). The control groups consisted of i) lean subjects
(mean BMI 25.6 kg/m2) enrolled for elective general abdominal surgery in
papers I and II (n = 22), and ii) morbidly obese subjects in papers III and IV.
The subjects in the lean control groups underwent only six hours’
preoperative fasting. Subjects with untreated systemic or pulmonary
hypertension, atrial fibrillation, pacemaker, unstable angina pectoris and
significant failure of heart valves and known difficult airway (i.e. need for
fiberoptic and/or video-assisted larygoscopy intubation) were excluded.
Data on diagnosed underlying co-morbidities, regular medication, patient
characteristics and preoperative loss of weight were collected preoperatively.
Prevalence of dyspnea and/or orthopnea was evaluated before and after the
preoperative RWL-preparation (I). Frequency of cardiopulmonary
investigations during the last 10 years was assessed preoperatively (III). For
calculation of BMI in kg/m² patients were weighed with measurement
accuracy of 100g. Primary and 30-day outcome, complications, length of stay
at the postoperative recovery unit (POP) and length of hospital stay (LOS)
were registered (I, III and IV). No sedative pre-medication was used due to
potential risk of hypoventilation related to severe obesity (97).
Assessment of heart function, filling pressures of the left ventricle, level of
venous return and rehydration was implemented by use of preoperative
transthoracic echocardiography (TTE) (I, III and IV) in addition to a
intraoperative mini-invasive pulse-contour device (FloTrac/Vigileo™) (IV).
28
Moreover, overall effects of perioperative volume therapy on intra-
abdominal pressure (IAP), renal function and filling pressures and
dysfunction of the heart were evaluated by intra- and postoperative IAP-
measurements (Foley catheter™), and by gathering pre- and postoperative
blood samples (serum electrolytes, pH, acid-base balance, creatinine,
estimated glomerulus filtration rate, N-terminal prohormone of brain
natriuretic peptide (NT-proBNP)) (IV) (167, 170-172). Blood samples were
collected on the day of surgery and on the first postoperative day between 6
and 6.30 am. The arterial blood samples were collected and analysed
immediately with a blood gas analyser (ABL 800 flex; Radiometer
Copenhagen, Denmark). The supine position for 5 minutes without extra
oxygen was compulsory before collecting these blood samples (II, IV).
Anesthesia and preoxygenation techiques used in this thesis All subjects enrolled in substudies II and IV were preoxygenated by the same
procedure and anesthetized by two different standardized protocols intended
for RSI (i.e. volatile (II) or total intravenous induction (IV)). Common
principles for RSI were followed – no mask ventilation was performed before
endotracheal intubation. Both preoxygenation and induction of anesthesia
were implemented in a “ramp” position created by one large and one small
pillow in addition to a slight upwards tilt of the operation table (20 - 30°)
(Figure 9) (43).
Protocol for preoxygenation and anesthesia induction, Paper II The logistics of the anesthesia method used is illustrated in Figure 11. One
minute prior to the preoxygenation period atropine 0.5 mg and propofol 20
mg were administered i.v. Atropine was used mainly for vagolysis and
propofol as a sedative and anxiolytic drug (i.e. to facilitate breathing through
the facemask system and decrease sympathetic tone (99, 173). The Kion
SC9000 XL anesthetic workstation (Siemens Elema, Solna, Sweden) was
used in this study. All subjects were preoxygenated for 2 minutes with a tight
face mask with FiO2 0.9, a fresh gas flow of 10 l/min and a continuous
positive airway pressure (CPAP) of +8 cmH2O. Two vital capacity breaths
with a 3 seconds inspiratory pause were mandatory during the
preoxygenation period. Next, still keeping the face mask tight, the
sevoflurane vapouriser was opened to 8 %. All subjects were then asked to
take 3 vital capacity breaths, now with sevoflurane 8 %, without inspiratory
pauses and unchanged FiO2 and fresh gas flow (104, 105). If the breaths
were clinically evaluated as too small, a fourth breath was requested. In each
subject, the sevoflurane vapouriser was altered to 3 % after 30 s. At this
point, propofol 1.5 mg/kg, alfentanil 20 µg/kg and suxamethonium 1 mg/kg
were administered intravenously as a rapid sequence bolus (approximately 1
ml/second of respective medicine) (94, 99). Dosing of propofol and
29
alfentanil was based on the IBW and doses of suxamethonium on the TBW
(47, 86, 115, 118, 174). The scavenging facemask system (Medivent,
Westfield, Massachusetts, USA) was used for possible volatile gasspill.
Clinically sufficient stage of anesthesia (i.e. loss of consciousness and onset
of effect of alfentanil) was determined by absence of the eyelash reflex and
presence of miosis. In addition, an appropriate level of muscle relaxation for
laryngoscopy was determined as when fasciculations in the face disappeared
and the jaw felt relaxed. The face mask was released and a direct
laryngoscopy was performed with a laryngoscope (a Macintosh blade and a
short handle). A stiff stylet was used in all endotracheal tubes. In order to
ensure optimal venous return all subjects were repositioned to a 5 - 10°
reverse Trendelenburg position immediately after a successful endotracheal
intubation (43).
Figure 11. The schematic illustration of rapid sequence intubation with sevoflurane,
propofol, alfentanil and suxamethonium. A patient in a 20 - 30 degrees reverse
Trendelenburg position. Reproduced from Pösö T. et al. Volatile rapid sequence
induction in morbidly obese patients. Eur J Anaesthesiol 2011 Nov;28(11):781-7 by
the permission of Wolters Kluwer Health (I).
30
During general anesthesia all subjects were slightly hyperventilated using a
pressure or volume controlled mode, positive endexpiratory pressure (PEEP)
+8 cmH2O, inspiration/ expiration ratio to 1:1, tidal volume approximately 7
ml/kg IBW. The lung recruitment manoeuvre was implemented to all
subjects ten minutes after intubation by holding +30 cmH2O pressure for 10
seconds. Anesthesia was maintained by sevoflurane (0.8 - 0.9 minimum
alveolar concentration, MAC), an infusion of remifentanil (0.20 - 0.35 µg/kg
IBW per minute) and vecuronium bolus 0.1 mg/kg IBW (71, 86, 97) .
Protocol for preoxygenation and anesthesia, Paper IV Preoxygenation was performed as described above. The Primus anesthetic
workstation (Dräger, Lűbeck, Germany) was used in this substudy. A
standardized total intravenous rapid sequence induction of anesthesia was
implemented in both groups. Anesthesia was inducted with atropine 0.5 mg,
propofol 2 mg/kg IBW, alfentanil 20 µg/kg IBW and succamethonium 1
mg/kg total body weight (II). Anesthesia was maintained with sevoflurane,
infusion of remifentanil and rocuronium or mivacuronium after
endotracheal intubation. Train-of-four monitoring was used in all subjects.
Dosing scalars for rocuronium and remifentanil were based on the IBW
approximation and clinical course (II). Bolus of remifentanil was
administered if necessary 1 µg/kg IBW. The perioperative infusion rate of
remifentanil was 0.20 µg - 0.35 µg/kg IBW. Sevoflurane was administered
by age-justed MAC-values. The target MAC-value was 0.8 - 0.9. No EEG-
based monitoring for depth of anesthesia was used. All subjects were
ventilated with tidal volume 8 - 9 ml/kg IBW, minute ventilation
approximately 95 ml/kg IBW, PEEP +8 cmH2O and I:E ratio 1:2. An
identical recruitment manoeuvre as in paper II was performed. A volume-
controlled respirator mode was used primarily. If problems with high airway
pressure occurred despite an adequate general anesthesia and
neuromuscular blockade, the following were considered i) pressure-
controlled ventilation mode, ii) I:E ratio 1:1 (if no auto-PEEP was observed),
iii) smaller tidal volumes and higher frequency to maintain desired minute
volume. However, tidal volumes was kept ≥ 8 ml/kg IBW to maintain
accuracy of the FloTrac-device. If the above steps did not reduce airway
pressure as desired, a reverse Trendelenburg position by 20 degree was
established (43, 127).
31
Echocardiography
Protocols for TTE
In this thesis two different investigation protocols were implemented for
transthoracic echocardiographic scanning. The “rapid” TTE protocol was
designed to be implemented with focus on fast and reproducible assessment
of venous return and left ventricle filling pressures regardless of body
habitus or BMI. This protocol could be used in any clinical situation with
need of rapid evaluation of the circulation. The “rapid” protocol was utilized
once in papers I and IV before surgery. In paper III, the more time-
consuming “comprehensive” protocol was implemented before surgery.
The transthoracic echocardiographic investigations were conducted by
ultrasound devices Sequoia-512 (Acuson-Siemens, Mountain View, CA) in
papers I, III and IV, in addition to Vivid 6 (GE, Vingmed, Horten, Norway)
in paper IV. All investigations were performed in accordance with current
guidelines (84, 175-177) by one experienced sonographer (cardiac
physiologist) to minimize investigation bias and maximize the level of
standardization of signal acquisition and analysis of echocardiographic data.
The mean values of three consecutive end-expiratory cardiac cycles were
analysed and used for statistic analysis. 2-D, M-mode, pulsed-wave (PW)
continuous, and colored Dopper were used (I, III and IV). In addition, tissue
Doppler imaging (TDI) was applied in paper III. Investigations were done
with subjects in a supine position at a preoperative room.
2-D and M-Mode measurements Standard acquisition projections were implemented (parasternal long axis
(PLAX), short axis (SAX), apical 4-chamber (A4C) and subcostal projections)
(I, III and IV) (Figure 12). Apical 2 (A2C) and 3 chamber projections were
used for visual assessment of left ventricular contractility only. The left
ventricle (LV) measurements and visual evaluation were made perpendicular
to the ventricular long-axis at the level of the mitral leaflet tips from PLAX
windows with 2-D. Left atrium anterior-posterior diameter in end-systole
(LAd) was measured from PLAX and was indexed to the total body surface
area (BSA). Also, LAd, left ventricular end-diastolic diameter (LVEDd), left
ventricular end-systolic diameter (LVESd), end-diastolic wall thickness in
left ventricle (septal and posterior walls) and right ventricular end-diastolic
diameter (RVEDd) were recorded from the 2-D images with electronic
caliper assuring an optimal orientation for measurements.
Maximum inferior vena cava diameter (IVCmax), minimum inferior vena
cava diameter (IVCmin) after a rapid sniff was recorded with 2-D images
assuring an optimal measurement orientation. The IVC collapsibility index
32
(IVCCI) was calculated by formula: IVCCI % = 100 % x (IVCmax – IVCmin)/
IVCmax. The IVC measurements were obtained from subcostal windows
approximately two centimetres from the junction of the IVC and the right
atrium, perpendicular to the IVC’s long-axis taking care of true IVCmax and
that IVCmin was not measured at another plane (149, 178, 179).
Left ventricular systolic function was assessed visually at all acquisition
windows and by left ventricle fractional shortening (FS) (I, III, IV). In
addition, ejection fraction (EF) was calculated from SAX areas (III). Left
ventricular end-diastolic (LVEDA) and end-systolic (LVESA) areas were
traced at mid-chamber level in SAX windows. A conventional formula for EF
calculation was applied: EF % = 100 % x (LVEDA – LVESA) / LVEDA (177).
In paper III, stroke volumes (SV) were measured by the left ventricular
outflow track (LVOT) method. Left ventricular outflow track diameter
(LVOTd) was measured in PLAX windows by 2-D only before volume-
challenge to minimize bias in statistic comparison of ΔSV. Mean values of 3
separate LVOTd were used in SV calculation. Right ventricular (RV) systolic
function was assessed visually if possible, and by measuring tricuspid
annular plane systolic excursion (TAPSE) with M-mode. A value < 16 mm of
TAPSE was used as cut-off indicating a global systolic RV impairment (176).
Conventional and Tissue Doppler imaging measurements Transmitral inflow and pulmonary venous inflow velocities were gathered
with PW from A4C projections. The PW-derived transmitral inflow pattern
was used in fast visual evaluation (I, IV) and for a comprehensive analysis
(III). Measurements were obtained with the sample volume at one
centimeter inside of LV and in the middle of the mitral annulus. The
maximum velocities Early (E) and late (A) velocities were measured at an
end-expiratory phase of the cardiac cycle. E/A ratio, deceleration time (Dt)
of E-wave and E/Dt ratio were measured and calculated. A Valsalva
manoeuvre was performed if signs of pseudo-normalized diastolic function
based on the transmitral flow pattern were detected (84, 175). In paper III,
tissue Doppler (TDI) velocities; systolic (Sm), E’- and A’- wave; were
collected from A4C projections at the mitral annulus. The E/E’ septum-ratio
was calculated (84).
Velocity time integrals of the left ventricular outflow track (VTI LVOT) were
obtained with PW from apical 5 chamber windows (A5C) (Figure 13). Mean
values of three consequtive end-expiratory VTI LVOTs were used for a stroke
volume calculation. Stroke volumes of the left ventricle in ml were calculated
by formula: SV = 0.785 x LVOTd² x VTI LVOT (78, 180). Continuous
Doppler was used to measure velocity of a possible tricuspid valve
insufficiency for calculation of a pressure gradient between the right
33
ventricle and the right atrium by the modified Bernoulli equation (ΔP = 4 x
V²) (176).
Evaluation of left ventricular filling pressures and pressure
dynamics
Left ventricular filling pressures (LVFP), measured by estimated pulmonary
capillary wedge pressures (ePCWP), were assessed non-invasively by
combining IVCmax and IVCCI (I). Elevated ePCWP ≥ 15 mmHg was
supposed to exist with > eRAP 10 mmHg. Ordinary LVFP, that is, ePCWP <
15 mmHg, was stated with eRAP-values ≤ 10 mmHg (181, 182).
In addition, evaluation of the compliance of the left ventricle (pressure-
volume relationship) was conducted (I, III). Signs of possible pathological
instability in filling pressures and decreased compliance of LV were assessed
by merging gathered information of diastolic properties of LV, level of
venous return and TDI measurements (Figure 6) (84).
Echocardiographic assessment and criteria for hypovolemia A conventional assessment of level of venous return (VR) to the heart was
made by combining size of IVC (IVCmax) and IVCCI. IVCmax and IVCCI
were converted to estimations of right atrial pressure (eRAP) (178, 179) as
following:
i) The conventional definition for eRAP 0 to 5 mmHg was used, i.e.
IVCmax ≤ 15 mm with concomitant high IVCCI (> 50 %),
ii) eRAP 5 - 10 mmHg was stated with IVCmax values between 15
to 21 mm regardless of IVCCI,
iii) IVCmax size > 21 mm and low IVCCI (< 50 %) was interpreted
as eRAP > 10 mmHg,
iv) IVCCI ≥ 80 % (considered as IVC collapse) and IVCmax < 15
mm was interpreted as eRAP -2 to 3 mmHg.
The criteria for the hypovolemic state, based on a low level of venous return,
were the presence of estimated right atrial pressures < 5 mmHg. Euvolemia
was stated with eRAP 5 - 10 mmHg and hypervolemia when eRAP was > 10
mmHg (I, III, IV).
34
Data analysis The echocardiographic data obtained were processed and analysed both on-
line and off-line. The rapid on-line analysis was implemented in papers I and
IV including an analysis of: IVCmax, IVCmin, IVCCI, LAd, LVEDd, FS, visual
assessment of left ventricular systolic function, visual assessment of the
pulsed-wave Doppler velocities of transmitral flow, both visual and TAPSE-
based assessment of systolic function of the right ventricle. Off-line
processing (I, III and IV) consisted of a comprehensive assessment of
diastolic function (Dt, E and A wave max velocities, E/A, E/Dt, E/E´ ratios),
measurement of stroke volumes and LV areas and calculation of ejection
fractions of LV. This process was carried out with commersially available
software (EchoPac, GE, Healthcare, Horten, Norway) and/or with the
Sequoia-512 device.
For overall evaluation of the usefulness of TTE as a preoperative modality,
feasibility, on-line time consumption and acquisition circumtances in both
mordbily obese and lean subjects were assessed. Time consumption for the
on-line process was measured by a timer (I, IV) (183). In addition, the intra-
observation bias for echocardiographic measurements was controlled (I).
35
Figure 12. The subcostal projection of the inferior vena cava and surrounding tissues
obtained by transthoracic echocardiography.
36
Figure 13. The apical 5 chamber (A5C) view of the heart. The pulsed wave (PW)
obtained flow curve of the left venricular outflow track (LVOT) for calculation of
stroke volumes of the left ventricle.
Fluids In this thesis both crystalloid and colloid fluids were administered. Products
used were: 6 % hydroxyethyl starch 130/04 balanced (Volulyte™, Fresenius
Kabi, Sweden) as colloid fluid and Ringer’s solution (Fresenius Kabi,
Sweden), NaCl 0.9 %, (Fresenius Kabi, Sweden) and buffered glucose
solution (25 mg/ml, Fresenius Kabi, Sweden) as crystalloids.
In preoperative (II, III, IV) and intraoperative (IV) rehydration, only colloid
fluids were infused. Antibiotics were mixed with NaCl 0.9 % or administred
directly in their commercially available form. In addition, minor amounts of
fluids were administered as i.v. anesthetics, intropic and vasoactive drugs,
NSAIDs and PONV prophylaxis.
37
Inotropic and vasoactive drugs Perioperative ephedrine and/or phenylephrine were used as intermittent i.v.
injection when necessary to ensure adequate tissue perfusion (MAP ≥ 65
mmHg), cardiac index (≥ 2.0) and heart rate (≥ 50/min) (II, IV) (184).
Furthermore, if systolic left ventricular failure was detected in preoperative
TTE, infusion of dobutamine 3 - 4 µg/kg IBW was started preoperatively
(IV).
Paper I Twenty eight morbidly obese subjects scheduled for bariatric surgery (the
morbidly obese group, MO) and 19 lean subjects (the control group, CG)
were consecutively enrolled in this observational study. CG consisted of
subjects scheduled for elective general abdominal surgery. The aim of the
study was to assess prevalence of preoperative hypovolemia and filling
pressures of the left ventricle in morbidly obese subjects that have been
prepared preoperatively by the rapid weight loss (RWL) diet, and compare
this to lean controls with conventional preoperative fasting. This assessment
was conducted by transthoracic echocardiography, with focus on the
protocol’s rapidity and reproducibility. (See the detailed description of the
TTE-protocol above in “Methods- Echocardiography”). All
echocardiographic investigations were performed prior to surgery. The
supine position was used during the TTE-scanning. Otherwise a semi-sitting
position was applied preoperatively.
Main outcome measures The main outcome measures were: i) level of preoperative venous return, ii)
level of LVFP, iii) assessment of biventricular systolic function, iv)
assessment and prevalence of impaired diastolic function in the left
ventricle, and v) evaluation of feasibility, time consumption and acquisition
quality for transthoracic echocardiography implemented by the study
protocol.
Moreover, prevalence of dyspnea and/or orthopnea before and after the
preoperative rapid-weight-loss preparation was assessed in order to evaluate
significance of the RWL-diet to left ventricular filling pressures.
Paper II Thirty four morbidly obese subjects scheduled for laparoscopic bariatric
surgery were included consecutively. The control group (CG) consisted of 22
lean subjects enrolled for elective abdominal surgery. The ideal body weight
was estimated with an equation height in cm - 100 for administration of
anesthetics drugs in both groups. All subjects were anesthetized by the same
38
anesthetist and nurses in order to maintain a high level of standardization
and avoid an inter-investigator bias.
In this study the technique for a rapid sequence induction of anaesthesia for
morbidly obese patients was developed and evaluated. The technique was
based on a combination of volatile and i.v. anesthetics (sevoflurane,
propofol, suxamethonium and alfentanil) and was designed to do the
following:
i) minimize risk for desaturation and hypoxia, i.e. maintain
spontaneous breathing as long as possible and to keep the
period of apnoea as short as possible before endotracheal
intubation,
ii) enable sustained lung recruitment during induction as long as
spontaneous breathing continued,
iii) assure hemodynamic stability, i.e. post-induction MAP goal ≥ 70
% of the baseline,
iv) generate good circumstances for endotracheal intubation,
v) minimize risk for post-induction awareness.
The detailed logistics of the method is described earlier in the chapter
“Anesthesia and preoxygenation techiques used in this thesis” and in Figure
11.
Before induction of anesthesia an infusion of glucose solution (25 mg/ml) at
1.5 ml/kg IBW per hour was initiated and approximately 500 ml colloid
fluids were infused in both groups. In morbidly obese subjects a continuous,
invasive blood pressure measurement was implemented (BD Arterial
Cannula and Transducer Blood Sampling Set). In CG an automatic non-
invasive blood pressure measurement was used. Arterial blood samples were
gathered and analysed immediately. Peripheral oxygen saturation (SpO2)
was registered directly after the preoxgenation and 1 minute after
endotracheal intubation. Blood pressure levels were registered before the
preoxygenation period and 3 minutes after the endotracheal intubation in a 5
- 10° reverse Trendelenburg position.
The anesthetic machine integrated timer was utilized to measure the time
periods of interest in the process of induction. Three periods were measured:
the spontaneous breathing time (SBT), the apnoea time (AT) and the total
time (TT). The definition for the SBT was the time from the beginning of the
administration of sevoflurane to the disappearance of spontaneous
breathing. The apnoea was detected by clinical signs and with the
39
capnograph. The AT was defined as the time from disappearance of
spontaneous breathing to a successful endotracheal intubation (AT = TT –
SBT) (Figure 11).
The definition of a successful endotracheal intubation was the sensation
and/or a clear visualisation of the endotracheal tube crossing the glottis and/
or as the first signs of expiratory flow in the capnograph (for the subjects
with the Cormack-Lehane scale 3 - 4).
Main outcome measures Time relationships for spontaneous breathing and apnoea in addition to
systolic and mean arterial blood pressures were measured for statistic
analysis as described above. Pre- and post-induction SpO2, frequency of
desaturation and MAC value after endotracheal intubation were registered.
The Mallampati and Cormack–Lehane scales were used for assessment of
the intubation circumstances between the groups. The suitability and
feasibility of the study method for RSI were evaluated from both
anesthetist’s and patients’ point of view.
Paper III Thirty four preoperatively RWL-prepared morbidly obese subjects scheduled
for bariatric surgery were consecutively enrolled in this substudy. The aims
of the study were to implement and evaluate effects of the preoperative,
individualized and ideal body weight (IBW) based volume challenge (VC) on
hemodynamics, stroke volume, and the level of venous return to the heart.
Effects of VC were evaluated by the comprehensive TTE-protocol
preoperatively. (See the detailed description of the TTE-protocol above in
“Methods”). All TTE investigations were performed in the awake state before
and after standardized intravascular volume challenge of 6 ml colloids/kg
ideal body weight (138, 185). The IBW was estimated with an equation
height in cm – 100. The volume challenge was implemented to all study
subjects for thorough assessement of the safety of the rehydration protocol.
Main outcome measures The main outcome measures were: i) level of venous return before and after
VC, ii) volume responsiveness; an increase of stroke volume ≥ 13 % was
considered to be a volume responder (137, 180, 186), iii) biventricular
systolic function before and after VC, iv) impact of VC on diastolic function
and the filling pressures of the left ventricle, and v) to evaluate feasibility of
dynamic and non-dynamic echocardiographic indices for VC in morbidly
obese subjects.
40
Paper IV Fifty morbidly obese subjects scheduled for bariatric surgery were
consecutively enrolled for the study. The aim of the study was to evaluate
need of perioperative hydration during laparoscopic bariatric surgery by
comparing conventional monitoring to a more advanced approach
(individualized goal-directed therapy, IGDT) (143, 146). A non-blinded
allocation of the subjects to the intervention group (n = 30) and the control
group (CG, n = 20) was conducted. The IBW was estimated with an equation
height in cm - 100 for administration of anesthetics drugs and fluids in both
groups.
In addition to pre- and/or intraoperative volume challenges, infusion of
buffered glucose solution (25 mg/ml) at a rate of 1.5 ml/kg IBW/h and i.v.
antibiotics (in total 550 ml crystalloids) were administrated after induction
of anesthesia, before pneumoperitoneum in both groups. Postoperative fluid
therapy during the stay at the postoperative recovery unit was identical
between the groups, that is, 850 ml crystalloids (antibiotics, paracetamol and
NSAIDs) and buffered glucose solution (50 mg/ml) at a fixed rate of 100
ml/h. Postoperative renal function, electrolyte and acid-base balance and
levels of pro-natriuretic peptides (N-terminal prohormone of brain
natriuretic peptide, Nt-proBNP) were analyzed in both groups (170, 171,
187). Urinary output was measured at POP only. Moreover, intra-abdominal
pressures were monitored in the intervention group. The first IAP
measurement was conducted in a supine position, before
pneumoperitoneum in general anesthesia ensuring zero train-of-four ratio,
zero PEEP and an expiratory pause of ten seconds. The pubic bone was used
as a reference level. The second measurement was conducted 4 hours
postoperatively without significant PONV and pain (visual analog scale, VAS
≤ 3/10) in a supine position. The perioperative logistics of the study is
summarized in the study flow chart (Figure 13).
In the control group a standardized conventional cardiovascular monitoring
was conducted (ECG, heart rate, non-invasive blood pressure measurements
and peripheral saturation (Sp02)). No preoperative rehydration was applied.
The intraoperative goals (MAP > 70 % of the pre-induction baseline and/or
≥ 65 mmHg, heart rate ≥ 50/min) were obtained by i.v. administration of
colloids 3 ml/kg IBW and/or ephedrine and/or phenylephrine.
In the intervention group, IGDT and conventional cardiovascular monitoring
similar to CG were implemented. Preoperative transthoracic
echocardiography (TTE) and perioperative mini-invasive pulse-contour
device (FloTrac/Vigileo™, Edwards Life sciences, Irvine CA, USA) were used
to obtain functional hemodynamic parameters needed for IGDT in two steps.
41
First, preoperative TTE scanning and rehydration was performed 45 minutes
before surgery. Second, maintained perioperative guidance of the fluid
therapy was conducted using the FloTrac-device. The preoperative
rehydration was implemented by 6 ml colloid fluids/kg ideal body weight if
low level of venous return was detected by TTE (III). The second TTE
investigation was performed to check the level of venous return. If remaining
hypovolemia was found additional colloids 3 ml/ kg IBW was infused.
Moreover, infusion of dobutamine 3 – 4 µg/kg IBW was initiated before
induction of anaesthesia if systolic left ventricular failure was detected in the
preoperative TTE. Stroke volume variation ≥ 12 % was used as a threshold
(137, 143, 146, 160, 188) for administration of additional colloids 3 ml/kg/
IBW during surgery (138). In addition to fluids, i.v. ephedrine and/or
phenylephrine were used when necessary to ensure adequate tissue
perfusion (MAP > 70 % of the baseline and/or ≥ 65 mmHg, cardiac index ≥
2.0 and heart rate ≥ 50/min) (184).
The data gathering The baseline for MAP and heart rate was registered in a supine position
before induction of anaesthesia in both groups. 5 minutes after intubation,
before pneumoperitoneum and i.v. antibiotics the conventional and the first
FloTrac-derived functional hemodynamic parameters (SVV, SV, cardiac
output and cardiac index) were collected. From then on, registration of
hemodynamic parameters was performed every 5 minutes. During
pneumoperitoneum, IAP levels were kept at approximately 12 – 14 mmHg
(always < 15 mmHg) to minimize risk of hemodynamic compromise (75, 93,
167). The FloTrac-guided fluid administration and monitoring was finished
in the end of surgery. Conventional monitoring was implemented at the
postoperative recovery unit in both groups.
Main outcome measures Mean arterial pressures and heart rates were measured before and after
induction of anaesthesia and during surgery for statistic comparison
between the groups. A comparison of fluids infused was conducted.
Postoperative urinary output and renal function were compared between the
groups. Analysis of effects of volume therapy on NT-proBNP-levels, intra-
abdominal pressures and functional hemodynamic parameters was
conducted in the intervention group.
42
Figure 13. The flow chart of the perioperative logistics in paper IV.
Abbreviations: IGDT, individualized goal-directed therapy; *, conventional monitoring was
conducted by ECG, heart rate, SpO2 and blood pressure measurements (non-invasively in the
control group and invasively in the intervention group); TTE, transthoracic echocardiography;
MAP, mean arterial pressure; SVV, stroke volume variation; CO, cardiac output; SV, stroke
volume of the left ventricle; RSI, rapid sequence induction; IAP, intra-abdominal pressure;
IBW, ideal body weight; ECG, electrocardiogram; POP, a postoperative recovery unit.
43
Statistics The data processing was done with Statistical Package for Social Sciences
(SPSS) version 18.0 (I and II) and with version 20.0 (III and IV). All data are
expressed as mean values ± SD if not otherwise stated. Levene’s test was
used to assess equality of variances of the data. Kolmogorov–Smirnov tests
for normality were performed. Two-tailed Student’s test and/or Mann-
Whitney U test were used for comparisons of mean values. Mann–Whitney
U test was used as a non-parametric test whether the variables were not
perfectly normally distributed and the number of cases was limited. When
appropriate, Chi-squared and/or Fisher’s Exact Tests were performed for
comparison of binominal data. Two-tailed p-values less than 0.05 were
considered statistically significant. The sample sizes for each substudy were
calculated to achieve power at 0.8 minimum (Power = 1 – β = 0.8) with α
level 0.05, β 0.2. The standard deviations of the primary variables that were
used for sample size calculations were estimations if relevant values could
not be found from the published data available.
Limitations This thesis has several limitations. The settings of the substudies per se
(single centre, not randomised, not blinded) may have been a potential
confounder. In addition, anesthesia was standardized per se, but neither
target controlled infusions (TCI) nor objective modalities for anesthesia
depth monitoring (for example bispectral index (BIS) monitoring) were
used. On the other hand, the experienced staff in bariatric surgery took care
of all subjects in the studies. IBW was estimated by a simple calculation
because of clinical simplicity of the equation. Thus, LBW was neither
determined by objective (direct) measurements, for example body-
impedance measurement, nor by more complicated equations intended to
estimate the LBW.
Transthoracic echocardiography is subject to significant limitations in obese
patients because of body habitus. In order to minimize investigator bias an
experienced sonographer for the subject is obligate and all investigations
were made by a single sonographer. Abnormal intra-abdominal and
intrathoracic pressures in obesity may have an impact on measurements of
inferior vena cava size and venous return to the heart (I, III, IV) (93).
The FloTrac-device is not validated in extreme obesity where reduced thorax
wall and pulmonary compliance and propensity for increased stiffness of the
left ventricle may have an impact on reliability of the FloTrac-data. Increased
intra-abdominal pressures may also jeopardize reliability of stroke volume
variation measurements but on the other hand IAPs were not significantly
44
increased in the substudy IV population. Furthermore, the intraoperative
invasive monitoring was implemented by a single modality. This may
increase a risk of incorrect decision making and fluid therapy during a
possible system failure in the FloTrac-device.
Statistical comparison of effects of fluid therapy on heart and renal function
between the intervention group and the control group could not be
conducted due to many drop offs in controls (IV). In addition, intra-
abdominal pressures were not measured in controls. In order to assess fluid
therapy and cumulative balance more comprehensively a comparison of pre-
and postoperative weight should have been valuable. Unfortunately, this was
not conducted in this thesis.
45
Results
Paper I: In the morbidly obese subjects (MO, n =28) mean BMI was 41.8
kg/m² (37 – 50.3) compared to lean individuals (CG, n =19) with mean BMI
25.6 kg/m² (20.8 - 29). Most morbidly obese subjects had been severely
obese over 20 years (20/28). Hypertension, asthma bronchiale, diabetes
mellitus, obstructive sleep apnea syndrome/obesity hypoventilation
syndrome (OSAS/OHS) and ischemic heart disease (IHD) were more
frequent in the morbidly obese group compared to lean controls. In the
morbidly obese group, prevalence of dyspnoea and/or orthopnea was higher
before the RWL-period compared to that on the day of surgery (i.e. post
RWL); 46.4 % and 10.7 % respectively. Preoperative loss of weight was 8.3 ±
2.1 % (4.4 - 12.2) and 11.1 ± 3.4 kg (5 - 18). No dyspnoea/orthopnea was
found in CG. These findings may depend on potential existence of pre-RWL
hypervolemia and high filling pressures of the heart (Table 1).
Low level of venous return was more common in the morbidly obese group
compared with the control group, that is, 71.4 % of MO were hypovolemic
vs. 15.8 % of lean controls; p < 0.001, odds ratio (OR) 13.3. In addition,
diameters of left atrium (PLAX) were shorter in the morbidly obese group
compared to CG. E/Dt ratios were not elevated. Left ventricular filling
pressures were elevated in few subjects in the morbidly obese group (3/28)
(Table 2). Left ventricular dysfunction was more frequent in MO. Impaired
diastolic function of the left ventricle were more commonly detected in the
morbidly obese group (57.1 %) than in controls (15.8 %); p = 0.006.
Conventional systolic failure was rare; one in MO hade impaired systolic LV
function (ejection fraction of LV < 50 %). Right ventricular systolic function
and pulmonary pressures appeared to be within normal limits in all patients.
The acquisition quality of echocardiography was poorer in MO compared to
CG. PLAX and SAX were considered as the most feasible projections in MO.
The most difficult to visualize was the right ventricle in A4C. The time-
consumption for the on-line investigation in MO was longer vs. the control
group (6.1 ± 1.97 minutes and 4.3 ± 1.1 minutes, respectively). Despite these
acquisition challenges, the assessment of preload and heart function could
be completed in 100 % of the patients. Reproducibility and intraobserver
variation (calculated for LA, IVC, E-wave and Dt) were adequate.
46
Table 1. Summary of patient characteristics, comorbidities and regular anti-
hypertensive medication (number of cases, mean values ± SD)
Parameter MO CG pT
Age (years) 44.6 ± 10.5 50.1 ± 12.7 NS
Gender, Female (%) 57.1 63.0 NS*
BMI (kg/m2) on the day
of surgery
41.8 ± 3.8 25.9 ± 2.64 < 0.001
Weight (kg) on the day of
surgery
123 ± 17.9 70.3 ± 10.3 < 0.001
Preoperative dyspnea
and/or ortopnea
13/28 0 < 0.001*
Waist circumference (cm) 136 ± 15.7 ND NA
Hypertension 16/28 3/19 ND
Diabetes mellitus 9/28 0 ND
OSAS/OHS 3/28 0 ND
Bronchial asthma 4/28 0 ND
Beta-blockers 8/28 1/19 ND
ACE/ARB 11/28 3/19 ND
Diuretics 2/28 0 ND
Calcium channel
blockers
2/28 0 ND
Abbreviations: BMI, body mass index; BSA, body surface area; NA, not applicable; ND, not
done; NS, not significant; T, independent sample t-test, equal variances not assumed; *, Fisher’s
exact test; OSAS, Obstructive sleep apnoea syndrome; OHS, Obesity hypoventilation syndrome;
ACE/ARB, angiotensin converting enzyme inhibitors/angiotensin receptor blockers; SD,
standard deviation of mean values; p, a p-value. The morbidly obese group (MO), n = 28; the
control group (CG), n = 19.
47
Table 2. Estimated right atrial pressures and left ventricular filling pressures
(number of cases and % of all cases)
Parameter MO CG p*
eRAP -3 to 2 or 0 to
5mmHg
20/28 (71.4%) 3/19 (15.8 %) < 0.001
eRAP -3 to 2 mmHg 5/28 (17.9 %) 1/19 (5.3 %) NS
eRAP 5 - 10 mmHg 5/28 (17.9 %) 11/19 (57.9 %) 0.005
eRAP > 10 mmHg
3/28 (10.7 %) 5/19 (26.3 %) NS
ePCWP < 15 mmHg 25/28 (89.3 %) 14/19 (73.7 %) NS
ePCWP > 15mmHg
Prevalence of
3/28 (10.7 %) 5/19 (26.3 %) NS
Hypovolemia (%) 20/28 (71.4 %) 3/19 (15.8 %) < 0.001
Euvolemia (%) 5/28 (17.9 %) 11/19 (57.9 %) 0.005
Hypervolemia (%) 3/28 (10.7 %) (5/19) (26.3 %) NS
Abbreviations: eRAP, estimated right atrial pressure; ePCWP, estimated pulmonary capillary
wedge pressure;*, Fisher’s exact test; p, a p-value; NS, not significant. The morbidly obese group
(MO), n = 28; the control group (CG), n = 19. Reprinted from Pösö T. et al. Rapid weight loss is
associated with preoperative hypovolemia in morbidly obese patients. Obes Surg. 2013 Mar;
23(3):306-13 by the permission of Springer (I).
Paper II: The mean BMI was 42.4 (36 - 56.7) kg/m² in the morbidly obese
group (n = 34) and 25.6 (19.5 - 30.4) kg/m² in the control group (n =22).
The mean age was 43.5 (18 - 63) years in morbidly obese subjects and 49.1
(20 - 68) years in controls. Most subjects were women: 61.8 % and 86.4 % in
the morbidly obese and control groups respectively.
The study protocol (Figure 11) implemented for preoxygenation and
induction of anesthesia was considered to be feasible, reproducible and safe.
No problems with compliance in vital capacity breathing with a tight
facemask were noticed. The induction of sleep was smooth, without muscle
twitches or undesirable movements in both groups. For most subjects, three
to four vital capacity breaths of sevoflurane were enough for disappearance
of the eye flash reflex. The circumstances for direct laryngoscopy were good
and all the endotracheal intubations were successful at the first attempt. No
aspiration was observed. No periods of desaturation or hypoxia were
48
registered; in fact, SpO2 was 100 % before and after endotracheal intubation
in all subjects in the study (Table 3).
Table 3. Summary of process parameters (mean values and range)
Parameter MO CG pT pMW
Spontaneous breathing
time
67.0 (48 - 91) 70.7 (50 - 88) NS NS
Apnoea time 44.8 (21 - 65)
45.7 (23 - 61) NS NS
Sp02 pre intubation 100 100 ND ND
Sp02 post intubation 100 100 ND ND
MAP pre intubation 94.2 (74 - 120) 95.7 (73 - 124) NS NS
MAP post intubation
74.3 (58 - 120) 77.8 (53 - 111) NS NS
MAC value post-
intubation
0.8 0.8 ND ND
Abbreviations: MAC, a minimal alveolar consentration value (MAC); SpO2, peripheral
saturation; MAP, mean arterial pressure ; NA, not applicable; ND, not done; NS, not significant;
T, independent sample t-test, equal variances not assumed; p, a p-value; MW, a non-
parametric Mann-Whitney U test. All post values were measured 3 minutes after intubation of
trachea. The morbidly obese group (MO), n = 34 and the control group (CG), n = 22.
The RSI-method implemented resulted in short apnoea times (AT) and long
spontaneous breathing times (SBT) in both groups. In the morbidly obese
group the AT was 44.8 (21 - 65) sec and the SBT was 67 (48 - 91) sec. In the
control group the AT was 45.7 sec (23 - 61) and the SBT was 70.2 sec (50 -
88). No significant differences in measured time periods were found. All
subjects were hemodynamically stable. An acceptable decrease in mean
arterial blood pressure from the pre-induction baseline was registered (21.2
% in morbidly obese group and 18.8 % in the control group). No significant
differences between the groups were registered in hemodynamic parameters.
In addition, the first age-adjusted MAC-values after endotracheal intubation
were measured to 0.8 indicating an appropriate level of general anesthesia
and, thus, a low risk of post-induction awareness (Table 3).
49
Paper III: Thirty-four morbidly obese subjects (mean BMI 41.8 ± 4.6
kg/m², body surface area (BSA) 2.3 ± 0.2 m²) were enrolled in the study.
Most subjects were women (23/34) with mean age of 42.8 ± 8.8 years.
Preoperative loss of weight in three weeks was 8.3 ± 1.9 % (11.3 ± 3.6 kg) of
TBW. Severe obesity had been long-lasting (≥ 15 years) in most patients
(24/34). Patient characteristics, comorbidities and medications are
summarized in Table 4. Preoperative risk assessment conducted with
objective methods was not comprehensive, that is, cardiac and pulmonary
investigations in the last 10 years before surgery were rare (Table 5).
Table 4. Patient characteristics, comorbidities and anti-hypertensive medication (%,
number of cases or mean values ± SD). The morbidly obese group (MO), n = 34.
Characteristics MO
Waist circumference (cm) 136 ± 14.7
BMI (kg/m²) at the day of surgery 41.8 ± 4.6
Height (cm) 170.8 ± 8.7
Weight (kg) at the day of surgery 122.5 ± 17.9
Smoker (n) 12/34
Dyspnoea (in MET < 4) (n)
13/34
Comorbidities
Hypertension (n) 17/34
Diabetes mellitus (n) 12/34
Bronchial asthma/COPD (n) 14/34
OSAS/OHS (n)
9/34
Medication
Beta-blockers 4/34 (11.8 %)
ACE/ARB 9/34 (26.5 %)
Calcium channel blockers 4/34 (11.8 %)
Diuretics 8/34 (23.5 %)
Combination therapy (consisting ≥ 2 of medications above) 9/34 (26.5 %)
Abbreviations: BMI, body mass index; OSAS, Obstructive sleep apnoea syndrome; OHS, Obesity
hypoventilation syndrome; COPD, chronic obstructive pulmonary disease; MET, metabolic
equivalent of task; SD, standard deviation of mean values; ACE/ARB, angiotensin converting
enzyme inhibitors/angiotensin receptor blockers.
50
Table 5. Preoperative cardiac and pulmonary investigations in the last 10
years (number of cases). The morbidly obese group (MO), n = 34.
Investigation MO
Echocardiography/Dobutamine stress echocardiography 3/34
Spirometry/lung function testing 4/34
Exercise testing / cardiopulmonary exercise testing 2/34
Single-photon emission computed tomography (SPECT) 0/34
Percutaneous coronary intervention (PCI) 1/34
Conventional systolic failure in LV and RV was infrequent; 2/34 and 0/34
respectively. Diastolic dysfunction (DD) of the left ventricle was commonly
seen; 64.7 % (22/34) of MO were classified into DD-grades I to III of IV.
Decreased dynamics of E/A-ratio were seen in association with a post VC
Valsalva manoeuvre (p = 0.016). Increased post-VC E-wave and A-wave
velocities were detected compared to baseline before VC (p < 0.001 and p <
0.001 respectively). No significant changes in E/A-ratios could be found.
Increase in E/E’-ratios were seen post-VC (p = 0.025), but these ratios still
remained below 10 (8.7 ± 2).
Preoperative hypovolemia (i.e. low level of venous return) was detected in
most subjects (24/34, 70.6 %). The hypovolemic state was more frequently
associated with female gender (p = 0.036), use of diuretics (p = 0.031) and
no use of ACE/ARB (p = 0.009). The post volume challenge hypovolemia
was rare; 5.9 % (2/34) patients were hypovolemic and 23/34 (67.6 %) of
patients were euvolemic. The post-VC hypervolemia was seen in 26.5 %
(9/34) of subjects. In these subjects diastolic dysfunction (p = 0.013), use of
calcium channel blockers (p = 0.048), male gender (p = 0.033) were more
frequent findings compared to post-VC euvolemic and hypovolemic subjects.
In addition, post-VC hypervolemia was associated with pre-VC hypovolemia
(p = 0.009) but not with pre-VC euvolemia (Table 6).
Most subjects were volume responders (29/34, p < 0.001). The preoperative
state of venous return was not associated with volume-responsiveness in this
study population. Medication with calcium channel blockers and systolic LV
failure were more frequently seen in non-volume responders (5/34)
compared to volume responders (p = 0.006, p = 0.015 respectively).
51
Table 6. Summary of hemodynamic parameters (% or number of cases or mean
values ± SD) before and after volume challenge.
Parameter MO pre MO post pT/Chi-2
MAP (mmHg) 91 ± 14.4 86.4 ± 9.5 NS
Heart rate/min 73.2 ± 13 74.1 ± 12.4 NS
Stroke volume (ml) 66.1 ± 12.2 79.5 ± 14.4 < 0.001
ΔSV (%) NA 16.6 ± 7 < 0.001*
Volume responder (%)
NA 29/34 (85.3 %) < 0.001*
Prevalence of hypovolemia 24/34 (70.6 %) 2/34 (5.9 %) < 0.001*
Prevalence of euvolemia 7/34 (20.6 %) 23/34 (67.6 %) < 0.001*
Prevalence of hypervolemia 3/34 (8.8 %) 9/34 (26.5 %) NS*
Abbreviations: MAP, mean arterial blood pressure; ΔSV, change of stroke volume; T,
independent sample t-test; *, Chi-Square or Fischer’s exact test; NS, not significant; NA, not
applicable; SD, standard deviation of mean values; n, number of cases; p, p-value; MO pre, the
morbidly obese group before volume challenge; MO post, the morbidly obese group after
volume challenge. The morbidly obese group (MO), n = 34.
Paper IV: Patient characteristics were similar in both groups. In the
intervention group BMI was 42.7 ± 5.3 kg/m², age 43 ± 14 years and 16/26
were women. In the control group BMI was 41.8 ± 4.3 kg/m², age 46 ± 11
years and 11/20 were women. Equal to other papers in this thesis,
hypertension, diabetes mellitus and bronchial asthma were common co-
morbidities. In the intervention group prevalence of preoperative
hypovolemia was 13/26, euvolemia 12/26 and hypervolemia 1/26 (Table 9).
Preoperative loss of weight (% of TBW) was similar between the groups (8.8
± 1.8 in the intervention group compared to 8.5 ± 2.0 in CG, NS).
No differences in time for surgery, consumption of anesthetics, length of stay
at POP, length of hospital stay and thirty-day mortality were found between
the groups. No pre- or postoperative renal failure was found. In the
intervention group postoperative Nt-proBNP levels were higher compared to
the preoperative baseline (280.4 ± 263.3 vs. 112.5 ± 157.7, respectively); p
= 0.007. Intra-abdominal pressures were not elevated at OR nor at POP. The
perioperative data is summarized in Table 7.
52
Abbreviations: SD, standard deviation of mean values; n, number of cases; mg, milligrams; min,
minutes; POP, the postoperative recovery unit; MAC, a minimal alveolar concentration of
sevoflurane; p, a p-value; T, an independent sample T-test; MW, a non-parametric Mann-
Whitney test; NS, not significant; ND, not done. The intervention group (IG), n = 26; the control
group (CG), n = 20.
In the intervention group, more preoperative colloid fluids were
administered compared to no preoperative rehydration in CG; p < 0.001.
During surgery there was no difference in fluids administered between the
groups. In total, more fluids were administered in the intervention group
compared to the control group; p = 0.009. Overall, more colloid and
crystalloid fluids were infused in the intervention group compared to CG (p
= 0.007 and p = 0.039, respectively) (Table 8).
Table 7. Summary of perioperative data in the intervention group (IG) and the
control group (CG) (n or mean values ± SD).
Parameter IG CG pT pMW
Operation time (min) 79.5 ± 15 86.6 ± 49 NS ND
MAC value intraoperatively 0.85 ± 0.1 0.83 ± 0.1 NS ND
Remifentanil (mg) infused
intraoperatively
2.14 ± 0.54 2.0 ± 1.3 NS 0.035
Time at POP in hours 18.1 ± 1.6 18.2 ± 2.3 NS ND
Diuresis at POP 1683 ± 741 1478 ± 331 NS ND
Cumulative fluid balance in ml
without perspiration
2298 ± 892 2013 ± 371 NS ND
Creatinine preoperatively 70 ± 19.6 76 ± 24.8 NS ND
Creatinine postoperatively 65.7 ± 18.1 72 ± 18.6 NS ND
Length of hospital stay 2.4 ± 2 1.7 ± 0.7 NS ND
30-day mortality 0/26 0/20 NS ND
Intra-abdominal pressure 9.52 ± 2.6 9.46 ± 3.8 NS ND
53
Table 8. Summary of fluids infused (in ml) in the intervention group (IG) and
the control group (CG) (mean values ± SD).
Parameter IG CG pT pMW
Total fluids 4053 ± 734 3499 ± 342 0.002 0.009
Total fluids (crystalloids) 3403 ± 752 3036 ± 396 0.039 0.07
Total fluids (colloids) 657 ± 263 463 ± 203 0.007 0.007
Colloid fluids infused
preoperatively
213 ± 204 0 < 0.001 <0.001
Abbreviations: SD, standard deviation of mean values; n, number of cases; ml, milliliters; p, a p-
value; T, an independent sample T-test; MW, a non-parametric Mann-Whitney test; NS, not
significant. The intervention group (IG), n = 26; the control group (CG), n = 20.
Mean arterial blood pressure levels were higher in the intervention group
compared to the control group both after induction of anesthesia (76 ± 15
and 62 ± 11 mmHg respectively); p = 0.001 and during surgery (78 ± 11 and
68 ± 10 mmHg, respectively); p = 0.001. Drop in blood pressure after
induction of anesthesia was 20.8 % in the intervention group and 38 % in the
control group. No tachycardia was registered (Table 10). More
phenylephrine was used in the intervention group vs. CG, 0.21 ± 0.22 and
0.12 ± 0.27 mg respectively; p = 0.011. Dobutamine infusion was used for
one patient in the intervention group.
In the intervention group heart rate (68 ± 11) and SVV (8.7 ± 2.9) were lower
after endotracheal intubation compared to mean intraoperative values (heart
rate 78 ± 11, SVV 11.5 ± 2; p = 0.002 and p = 0.001, respectively). In
addition, lower stroke volumes (66 ± 16 ml), higher heart rate (75 ± 14) and
higher SVV (15.7 ± 4.8) were registered after reverse Trendelenburg
positioning and pneumoperitoneum compared to post-intubation values (SV
78 ± 20 ml, heart rate 68 ± 11, SVV 8.7 ± 2.9; p = 0. 022, p = 0.001, p =
0.017, respectively). No statistical change in cardiac index was registered
(Table 9).
54
Table 9. Summary of perioperative hemodynamic parameters in the intervention group
(IG) (mean values ± SD or n).
Parameter IG preop IGpost
intub
IGpost rT IG intraop pT
MAP (mmHg) 96 ± 11 76 ± 15 75 ± 14 75 ± 9 0.001†
Heart rate/min 74 ± 12 68 ± 11 75 ± 14 78 ± 11 0.017†† 0.002†††
Stroke volume (ml) NA 78 ± 20 66 ± 16 70 ± 14 0.022††
SVV NA 8.7 ± 2.9 15.7 ± 4.8 11.5 ± 2 0.001††,†††
Cardiac output
(L/min)
NA 5.2 ± 1.3 5.0 ± 1.5 5.4 ± 1.3 NS
Cardiac index
NA 2.3 ± 0.6 2.2 ± 0.6 2.4 ± 0.5 NS
eRAP < 5mmHg 13/26 NA NA NA NA
eRAP 5 - 10 mmHg 12/26 NA NA NA NA
eRAP > 10 mmHg 1/26 NA NA NA NA
Abbreviations: MAP, mean arterial blood pressure; SVV, stroke volume variation; eRAP,
estimated right atrial pressure; T, independent sample t-test; rT, a reverse Trendelenburg
position; IG preop; preoperative baseline mean values in the intervention group; IG post intub,
post intubation mean values in the intervention group; IG post rT, mean values in the
intervention group 5 minutes after re-positioning to rT; IG intraop, intraoperative mean values
in the intervention group; p, a p-value; †, a p-value between preoperative baseline and post
intubation mean values; †† a p-value between post intubation and post rT mean values; †††, a p-
value between post rT and intraoperative mean values; NS, not significant; NA, not applicable;
SD, standard deviation of mean values; n, number of cases. The intervention group (IG), n = 26.
55
Table 10. Summary of perioperative hemodynamic parameters in the intervention
group (IG) and the control group (CG) (mean values ± SD).
Parameter IG CG pT pMW
MAP T0 96 ± 11 100 ± 12 NS ND
MAP T1 76 ± 15 62 ± 11 0.001 0.001
MAP T2 74 ± 11 69 ± 15 NS 0.051
MAP T3 78 ± 11 68 ± 10 0.002 0.001
Heart rate T0 74 ± 12 74 ± 14 NS ND
Heart rate T1 68 ± 11 66 ± 7 NS ND
Heart rate T2 75 ± 11 78 ± 15 NS ND
Heart rate T3 79 ± 11 75 ± 11 NS ND
Abbreviations: MAP, mean arterial pressure; T0, preoperative baseline mean values in a supine
position as awake; T1, mean values 5 minutes after endotracheal intubation; T2, mean values 5
minutes after re-positioning to a reverse Trendelenburg position; T3, intraoperative mean
values; SD, standard deviation of mean values; n, number of cases; p, a p-value; T, an
independent sample T-test; MW, a non-parametric Mann-Whitney test; NS, not significant; ND,
not done. The intervention group (IG), n = 26; the control group (CG), n = 20.
56
Discussion
This thesis describes a comprehensive perioperative management of
morbidly obese individuals scheduled for bariatric surgery. In morbid
obesity perioperative cardiovascular and respiratory stability and, hence,
enhanced recovery, can be achieved by implementing strict and proven
methods of anesthesia (97) and fluid therapy (III, IV) (41, 85).
The key messages of papers I, III and IV were that i) the RWL- preparation
prior to bariatric surgery may expose morbidly obese patients to significant
dehydration (I), ii) the preoperative rehydration regime implemented by
colloids 6 ml/kg IBW was found to be a suitable treatment to obtain optimal
levels of venous return (III) and, iii) preoperative rehydration may increase
hemodynamic stability during intravenous induction and even maintenance
of anesthesia without risk of postoperative complications. In addition,
conventional intraoperative cardiovascular monitoring seems to be a
sufficient approach in non-complicated bariatric surgery (IV).
Much focus should be placed on cardiovascular assessment and optimization
of morbidly obese patients (I, III, IV) (38, 41, 45, 93). Non- and/or mini-
invasive cardiovascular monitoring in combination with targeted IBW-based
rehydration should be considered to increase thorough perioperative
hemodynamic stability. Cardiovascular optimizing of morbidly obese
individuals should be initiated already before anesthesia induction and
surgery (III, IV) (185). Preoperative screening of a level of venous return,
assessment of filling pressures in the left ventricle, biventricular function of
the heart should be included in management of these high-risk patients to
increase perioperative safety. For this purpose, transthoracic
echocardiography was shown to be a feasible preoperative modality, even in
morbid obesity (I, III, IV). Monitoring of preoperative level of venous return
and cardiac function has several potential advantages: i) judgment of
individual targets without bias of anesthetic vasodilatation is facilitated, ii)
instability during induction of anesthesia is minimized, iii) possibility for
more precise planning of vasoactive/inotropic medication and additional
volume therapy during surgery is generated and, iv) intraoperative
monitoring is facilitated with “the preoperative data” in mind (IV) (152, 154).
Stable biventricular filling pressures are fundamental throughout the
perioperative period in bariatric surgery in order to reduce the physiological
stress of anesthesia and surgery (41, 97). Hemodynamic instability may
occur particularly during induction of anesthesia and pneumoperitoneum
(38, 75, 93). The results of paper IV may indicate that not only the amount of
57
fluids but the timing of rehydration may play a key role for cardiovascular
intraoperative stability - both post-induction and intraoperative mean
arterial blood pressures were higher in the intervention group with
preoperative rehydration vs. the control group. Thus, euvolemia is advocated
in bariatric surgery (41, 75, 93) and should be reached before induction of
anesthesia (I - IV).
In morbidly obese individuals scheduled for general surgery,
overreplacement of fluids may lead to respiratory complications, including
pulmonary strain/edema that necessitates non-invasive ventilatory support
and monitoring at a higher level of care than an ordinary postoperative
recovery unit (41). In addition, hypervolemia may increase perioperative
bleeding (189). On the other hand, insufficient volume therapy may lead to
organ hypoxia and acute renal failure. Hence, proper monitoring of
rehydration is crucial for highest perioperative safety for this patient group
(I, III, IV) (45, 85, 185, 190).
However, at the moment, publications concerning perioperative fluid
therapy regimes in severe obesity are few and are not based on general
consensus (41, 85). To my knowledge, papers I, III and IV are the first works
available with focus on preoperative hydration balance and fluid
management in this patient population. This lack of published information
was reflected in a recent consensus statement for bariatric anesthesia
management (97) where fluid management is not mentioned at all.
Nevertheless, based on the results of paper IV, the perioperative need of
fluids was approximately 800 ml per hour (11 ml/kg IBW/h) during surgery
plus preoperative colloid fluid bolus 6 ml/kg IBW. These results are in
concordance with a recent work by Jain et al. (85) indicating that “liberal”
rehydration (190, 191) in bariatric surgery may not be needed.
In patient populations with propensity for heart failure, e.g. individuals
scheduled for bariatric surgery, the fluid therapy should be implemented
preferably with on-line knowledge of volume responsiveness, diastolic
properties and compliance of the left ventricle. This kind of information
during rehydration can be achieved by echocardiography and Doppler
indices (Figure 6) (III) (78, 154). In this context, assessment of diastolic
properties of the left ventricle, evaluation of E/A-ratio dynamics is a robust,
reproducible and rapid way to obtain on-line information of pressure-
volume relationship of LV (III) (78, 84). Tissue Doppler imaging is a useful
modality in comprehensive cardiac diagnostics. However, monitoring
volume challenge by use of TDI gives no additional information with a
critical impact for bed-side decision making. Thus, monitoring conventional
dynamic transmitral indices together with change of stroke volume (ΔSV)
58
provides sufficient information about pressure–volume relationship in LV,
volume responsiveness and limitations in global stressed volume (III) (78,
192). In addition, it was confirmed that where there are physical limitations
for signal acquisition related to body habitus as in morbid obesity, detailed
comprehensive assessment of filling pressures can be difficult and time-
consuming (III).
In addition, echocardiography can also be applied preoperatively during
spontaneous breathing (154). Most modalities that produce dynamic data of
hemodynamics (e.g. FloTrac, PiCCO, Cardiac Q) are validated only for use
during mechanical ventilation with sufficient tidal volumes and, hence,
cannot be utilized in preoperative optimizing protocols during spontaneous
breathing (IV) (144). However, assessment with echocardiography is a single
assessment compared to other available modalities that are designed to
gather continuous data. Thus, the best results may be reached by a combined
and strategic use of these modalities (IV) (144, 145, 153) (Figure 10).
Continuous cardiovascular monitoring allows an anesthetist to react on
hemodynamic instability promptly and precisely. Traditional perioperative
“in need” approach for volume therapy with conventional intermittent
monitoring may lead to fluctuating hemodynamics, suboptimal organ
perfusion, and potential over-replacement of i.v. fluids with risk of
postoperative respiratory distress during prolonged surgery in particular
(137, 193).
The FloTrac was the modality of choice in this thesis due to existing
validation data, availability in our clinic, relative feasible and rapid set-up
(only an arterial line needed). However, invasive intraoperative monitoring
by the FloTrac-device gave no additional information on hemodynamics with
critical impact in our practice, where no difference in fluids administered
during surgery was found. There was no difference in length of stay at POP,
length of hospital stay or postoperative complications between the groups in
paper IV (Table 7). On the other hand, time for surgery was relatively short
in this study population. Thus, it should be kept in mind that the value of
continuous cardiovascular monitoring may be augmented during prolonged
or complicated surgery (85, 137). In addition, when comparing set-up times
of the FloTrac to assessment by transthoracic echocardiography, the TTE is
clearly superior. The time spent for obtaining hemodynamic data by TTE was
6.4 ± 2.3 minutes compared to 18.6 ± 3.3 minutes for the FloTrac device (p <
0.001). From the economical point of view, TTE is even cheaper in everyday
practice without catheter costs.
The volume therapy used to obtain euvolemia in this thesis was based on the
standardized combination of crystalloid and colloid fluids. Colloids were
59
used in volume challenges only (II, III and IV). In fact, this kind of
combination has shown to increase the glomerular filtration rate and the
clearance of crystalloids (194) and, hence, may protect individuals with
narrowed cardiorespiratory limits against hyper-hydration. Thus, combined
administration of these fluids in general may be motivated despite of
somewhat restrictive recommendations for use of colloids at the moment
(195). This subject should be studied further in morbidly obese subjects
scheduled for general surgery in particular.
Table 11 summarizes some essential hemodynamic issues that bariatric
anesthetists and surgeons should take into account for increased safety and
to cut complication rates and length of hospital stay in morbidly obese
individuals.
60
Table 11. Hemodynamic considerations in morbid obesity
Point of
interest
Principles “Caution” Methods Modalities
Level of
venous
return and
biventricular
filling
pressures of
the heart
Venous return
stability
Afterload
stability
Pressure-
volume stability
of LV
Euvolemia
Optimal
positioning
Avoid hypo
/hypervolemia
Avoid excessive
vasodilatation
Level of IAP
Preoperative
volume
challenge
Intraoperative
volume
challenge
Vasoactive
medication
Preoperative
TTE
Intraoperative
non/mini-
invasive
monitoring,
(TEE)
Foley/direct
measurement by
the surgeon
Contractility Preserved/
increased
contractility
Optimal
biventricular
filling pressures
Slight
pulmonary
vasodilatation
Arrhythmias
Avoid excessive
vasoplegia
Avoid hypoxia
and hypercapnia
Moderate
decreased
sympathetic
activity only
RV failure
Low-dose
inotropic
medication
(dobutamine)
Perioperative
inodilatators in
case of severe
HF
(levosimendan,
milrinone)
Adequate
intraoperative
administration
of anesthetics
Preoperative
TTE
Intraoperative
non/mini-
invasive
monitoring,
(TEE)
Consider PA in
severe RV failure
Assessment of
IBW, LBW
Renal
function
Stabile RAAS
Euvolemia
Avoid excessive
hypotension
Avoid high
IAPs
Preoperative
volume
optimizing
Preop TTE,
Intraop
non/mini-
invasive
monitoring,
Foley catheter
Abbreviations: TTE, transthoracic echocardiography; TEE, transoesophageal echocardiography;
HF, heart failure; RV, the right ventricle; PA, a pulmonary catheter; RAAS; the renin-
aldosterone-angiotensin system; IBW, ideal body weight; LBW, lean body weight; IAP, intra-
abdominal pressure; preop, preoperative; intraop, intraoperative.
61
As discussed earlier in the Background part of the thesis (“Obesity and the
respiratory system”), risk of desaturation is increased in morbidly obese
individuals during induction of anesthesia in particular. Thus, most effective
and safe techiques for preoxygenation and anesthesia induction are
addressed. In the anesthesia technique described in paper II, sevoflurane
was combined with propofol, alfentanil and suxamethonium, and was
demonstrated to be a safe method for rapid sequence induction regardless of
BMI without episodes of desaturation. In addition, minimal compromise of
hemodynamics was attained (II) (Table 3, Figure 11).
To maintain spontaneous breathing as long as possible during induction of
anesthesia may be fundamental regarding to prolong “the safety time period”
for laryngoscopy (i.e. decrease risk of desaturation). This can be resolved in
different ways, including the use of volatile anesthetics during induction (II)
or other i.v. drugs that have minor depressive impact on the respiratory drive
(196, 197). Volatile induction conducted by sevoflurane may have several
advantages in morbidly obese individuals in particular. Sevoflurane causes
bronchodilatation and decreases respiratory resistance (198). In addition, in
morbid obesity efforts to improve or even normalize ventilation/perfusion
ratio before surgery may be fundamental for adequate oxygenation.
Therefore, as described in this thesis, utilizing sevoflurane together with high
FiO2 and vital capacity breathing in the beginning of a RSI sequence allows
continued recruitment of lungs during induction of sleep and, hence, may
increase the quality of preoxygenation (II) (Figure 11). This procedure may
have major advantages in patients with excessive body mass, particularly for
abdominal, thoracic or face obesity, especially in obese patients with
concomitant pulmonary pathology such as bronchial asthma and/or chronic
obstructive pulmonary disease (199). In addition, accordingly to the results
of paper II, use of sevoflurane during the induction process may reduce risk
of post-induction awareness (post-intubation MAC 0.8) (Table 3).
Moreover, it is clear that prevalence for cardiovascular co-morbidities is
increased in morbidly obese individuals (38, 41). This should be taken into
account regarding the choice of anesthetics. Volatile anesthetics, e.g.
sevoflurane, have cardioprotective properties that should be utilized in
management these individuals with increased risk of perioperative
cardiovascular adverse events (200, 201). Thus, use of volatile anesthetics
already in induction of anesthesia (II) may function as volatile
preconditioning and, hence, reduce cardiovascular adverse events.
As discussed earlier in this thesis, a proper choice, dosing and speed of
administration of opiates, hypotics and neuromuscular blocking agents are
the cornerstones for safe induction of anesthesia at the moment (Figure 7).
62
An anesthetist must secure sufficient speed for injection to avoid awareness
and, on the other hand, overdosing. The hyperdynamic circulation in
addition to possible pre-induction anxiety in morbidly obese individuals
should be taken into account before administration of hypnotics (86, 94, 99).
In general, sedatives are not recommended as premedication due to
respiratory co-morbidities (41, 45, 93). In this thesis (II), as a substitute of
sedative premedication, a bolus of propofol was given before pre-
oxygenation (20 mg i.v.). This may facilitate induction of sleep in morbidly
obese individuals due to reduction of sympathetic activity and hyperdynamic
circulation by the drug. In addition, 30 sec vital capacity breathing with
sevoflurane may have had equivalent effects as propofol (Figure 11).
Necessity of RSI in morbidly obese individuals has been questioned in recent
guidelines (33, 97) for bariatric surgery, and is recommended only with
history of gastrooesophagal regurgitation. Regardless to the approach chosen
for induction (i.e. RSI or pre-intubation mask-bag ventilation) an early
injection of neuromuscular blocking agents during the induction process
may be advocated for easier mask ventilation and/or rapid endotracheal
intubation. In many severe obese individuals proper mask ventililation is
possible only after i.v. injection of these drugs (II) (97).
Nevertheless, RSI can also be conducted in other indications than increased
risk of endotracheal aspiration. In addition to the obvious risk of difficult
mask-bag ventilation per se, it must be underlined that mordbily obese
individuals have considerably increased risk of rapid desaturation and
hypoxia during hypoventilation and/or apnoea due to decreased functional
residual capacity, increased intra-abdominal pressure, cranial displacement
of diaphragm, increased tendency to atelectasis and shunt fraction (II) (45).
Moreover, in contrary to common difficulties in face mask ventilation,
endotracheal intubation has been shown to be relatively easy (II) (122). For
these reasons, in my opinion, mask-bag ventilation should be avoided when
possible and a straightforward rapid sequence induction is advocated in
proper positioning (a “ramp” position) and adequate preoxygenation (125).
Thus, in this thesis (II, IV), RSI was implemented in all study subjects to
avoid mask-bag ventilation in addition to conventional indications for RSI
(111).
63
Conclusions
Paper I: Low level of venous return and impaired diastolic function of the
left ventricle was more common in the RWL-prepared morbidly obese group
compared to the lean control group with ordinary preoperative fasting.
Caution must be taken regarding the level of venous return in subjects
scheduled for bariatric surgery with significant preoperative weight loss.
Preoperative transthoracic echocardiography is a robust modality for
assessment of level of venous return and cardiac function even in morbid
obesity.
Paper II: The combined RSI-technique conducted by sevoflurane, propofol,
alfentanil and suxamethonium was found to be a cardiorespiratory stable
and practical method for RSI regardless of BMI. In addition, minimal risk of
awareness and good circumtances for endotracheal intubation by direct
laryngoscopy were established by the method.
Paper III: IBW-estimates and appropriate monitoring are the key issues for
feasible and safe fluid management in severe obesity. The standardized
volume challenge of 6 ml colloids/kg IBW was shown to be suitable for
preoperative rehydration of RWL-prepared morbidly obese individuals.
Euvolemia was achieved in most subjects. No association between the
preoperative state of venous return and volume-responsiveness was found.
Majority of the morbidly obese subjects were volume responders. In this
patient population, use of conventional Doppler indices were more suitable
compared to tissue Doppler, giving sufficient information on pressure-
volume correlation of the left ventricle during rehydration.
Paper IV: Increased perioperative cardiovascular stability may be reached
by preoperative rehydration. The management of rehydration should be
individualized. Preoperative screening and optimizing of the level of venous
return may be needed in morbidly obese individuals scheduled for bariatric
surgery. Invasive perioperative monitoring may provide additional
information of hemodynamics, but is without critical impact in
uncomplicated bariatric surgery. Thus, conventional intraoperative approach
for cardiovascular monitoring seems to be sufficient for the purpose.
64
Future implications
At the moment, in modern anesthesia management, both volatile anesthetics
and i.v hypotics are usually administered in combination with opiates.
However, opiate drugs have undesired side-effects as respiratory depression
and increased risk of post operative nausea and vomiting (116). When used
as a single drug and low-dose (e.g. fentanyl < 1-2 µg/kg IBW) these side
effects are minimal. But, in combination with other drugs (e.g. midazolam,
propofol and/or sevoflurane), opiates cause significant respiratory
depression due to synergistic physiological effects (110). Thus, to diminish
these concerns and to optimize postoperative recovery period, use of opioids
should be reassessed and perhaps minimized. Even an opiate free
multimodal approach for induction and maintenance of anesthesia in
morbidly obese individuals has been described. In this concept, several non-
opiate drugs in various combinations can be applied. Most useful and
promising drugs are α-2 agonists (for example clonidine and
dexmedetomine), ketamine, lidocaine, corticosteroids and beta-blockers
(such as esmolol) (86, 196, 197, 202-205). In future, beta-blockers may also
play an important role in postoperative pain management and, hence,
contribute in the concept of “the opiate free perioperative approach” as a
standard drug (203).
Nevertheless, a multimodal opiate-free approach for induction of anesthesia
without a hypnotic-opiate synergy may be a challenge regarding to e.g.
awareness, circumstances for laryncoscopy and cardiorespiratory responses.
On the other hand, to minimize synergistic effects of drug combinations
(such as fentanyl or remifentanil plus propofol or midazolam) on respiratory
drive and, hence, maximize ability for spontaneous breathing (II) (106, 110,
197), may be a cornerstone for increased patient safety in morbidly obese
individuals in particular. However, at the moment, the evidence may be too
sparse to implement opiate-free approaches for induction and maintenance
of anesthesia in clinical practice (202, 206). Prospective randomized studies
in this concept are warranted.
In addition, routine use of body impedance measurements for more precise
assessment of lean body mass, TCI-models that are adjusted for severe
obesity may be essential for increased patient safety and enhanced recovery
(97). Moreover, reliable, feasible and economical non-echocardiographic
modalities for standardized scanning of venous return (112) and function of
the heart are needed. Continuous non-invasive cardiovascular monitoring
that is user-friendly and easy to implement in practise without need of
systematic education initiative is addressed.
65
In general, it should be underlined that morbidly obese individuals may
appear as three different categories in need of surgery: i) in non-bariatric
surgery, ii) in bariatric surgery, and iii) in general surgery after bariatric
surgery. All these patient categories have different hemodynamic,
respiratory and gastrointestinal characteristics and, hence, challenging the
anesthesia praxis further. At the moment, the evidence of potentially altered
physiological characteristics in post-bariatric surgical individuals from an
anesthesiological point of view is very sparse (207). More studies comparing
these patient categories with each other are needed for better understanding
of impact of obesity and bariatric surgery in particular.
66
Acknowledgements First, I would like to show my greatest acknowledgements to my supervisor
Doris Kesek and to co-supervisors Ola Winsö and Roman A’roch. Most of all
I appreciate the thorough confidence on my development during this project
and capacity to complete the issues needed.
I also wish to show my appreciation to Michael Haney for showing me “the
straightforward academic attitude” and for excellent language support.
In addition, I would thank the administration staff at Umeå University,
Ullagreta Gidlund and Göran Johansson in particular, for all necessary work
that you have done for this PhD project.
The paper II is dedicated to the memory of my colleague and first supervisor
for this project, Staffan Andersson, who died suddenly in December 2010. In
addition, I would thank the staff at Luleå University of Technology for the
work done during the first steps of this project.
Thanks to all colleagues at Sunderby hospital. You have given me more
”spirit” to finish this work both by your encouraging comments and
(constructive) criticism.
Thanks to the FoU-unit at Norrbotten County Concil (NLL) for both
economical and scientific support for carry out this work. Thanks to Robert
Lundqvist for statistical support. Karin Zingmark and Mats Eliasson – you
have encouraged me to believe that the clinical research in the field of
anesthesiology and “the academic sprit” can and must be established at
Sunderby hospital.
And, at last but not least - the major appreciation and thanks to my family,
Kajsa, Astrid, Johan and Karl, for giving me endless support and opportunity
to complete this work.
67
Economical support The research was supported by the Norrbotten County Council and Arnerska
Research Fund.
Permissons and reprints Some of the images, tables, and part of the text of this thesis are
reproductions from the original articles. The adequate permissions for reuse
of the material used in this thesis have been acquired from the publishers
concerned.
68
References
1. WHO. Obesity: preventing and managing the global epidemic. World Health Organization Technical Report Series. 2000;894(i-xii):1-253.
2. WHO, Obesity and overweight [Internet]. 2010. Available
from: http://www.who.int/mediacentre/factsheets/fs311/en/index.html.
3. Deitel M. Overweight and obesity worldwide now estimated to involve 1.7 billion people. Obes Surg. 2003;13(3):329-30.
4. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ,
Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-55.
5. Sturm R. Increases in morbid obesity in the USA: 2000-2005. Public Health. 2007;121(7):492-6.
6. Lilja M, Eliasson M, Stegmayr B, Olsson T, Soderberg S. Trends in obesity and its distribution: data from the Northern Sweden MONICA Survey, 1986-2004. Obesity (Silver Spring). 2008;16(5):1120-8.
7. Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ,
Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347(5):305-13.
8. Bjorntorp P. Obesity. Lancet. 1997;350(9075):423-6.
9. McClean KM, Kee F, Young IS, Elborn JS. Obesity and the lung: 1. Epidemiology. Thorax. 2008;63(7):649-54.
10. Crummy F, Piper AJ, Naughton MT. Obesity and the lung: 2.
Obesity and sleep-disordered breathing. Thorax. 2008;63(8):738-46.
11. Mokhlesi B, Tulaimat A, Faibussowitsch I, Wang Y, Evans AT. Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. Sleep Breath. 2007;11(2):117-24.
12. Diaz ME. Hypertension and obesity. J Hum Hypertens. 2002;16 Suppl 1:S18-22.
13. Peterson LR. Obesity and insulin resistance: effects on cardiac
structure, function, and substrate metabolism. Curr Hypertens Rep. 2006;8(6):451-6.
69
14. Wang Y, Chen X, Song Y, Caballero B, Cheskin LJ. Association between obesity and kidney disease: a systematic review and meta-analysis. Kidney Int. 2008;73(1):19-33.
15. Lotia S, Bellamy M. Anaesthesia and morbid obesity.
Continuing Education in Anaesthesia, Critical Care & Pain. 2008;8(5):151.
16. Kopelman PG. Obesity as a medical problem. Nature. 2000;404(6778):635-43.
17. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;28:1083-96.
18. Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B,
Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741-52.
19. Sjostrom L, Gummesson A, Sjostrom CD, Narbro K, Peltonen M, Wedel H, et al. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lancet Oncol. 2009;10(7):653-62.
20. Nugent C, Bai C, Elariny H, Gopalakrishnan P, Quigley C, Garone M, Jr., et al. Metabolic syndrome after laparoscopic bariatric surgery. Obes Surg. 2008;18(10):1278-86.
21. Hakala K, Mustajoki P, Aittomaki J, Sovijarvi AR. Effect of
weight loss and body position on pulmonary function and gas exchange abnormalities in morbid obesity. Int J Obes Relat Metab Disord. 1995;19(5):343-6.
22. Zavorsky GS, Hoffman SL. Pulmonary gas exchange in the morbidly obese. Obes Rev. 2008;9(4):326-39.
23. Neovius M, Narbro K, Keating C, Peltonen M, Sjoholm K, Agren G, et al. Health care use during 20 years following bariatric surgery. JAMA. 2012;308(11):1132-41.
24. Sjostrom L, Peltonen M, Jacobson P, Sjostrom CD, Karason
K, Wedel H, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56-65.
70
25. Hewitt S, Humerfelt S, Sovik TT, Aasheim ET, Risstad H, Kristinsson J, et al. Long-Term Improvements in Pulmonary Function 5 Years After Bariatric Surgery. Obes Surg. 2014.
26. The expert group rapport of the national guidelines for
bariatric surgery (NIOK), Sweden [Internet]. 2009. Available from: www.sfoak.se/wp-content/niok_2009.pdf.
27. Henrickson HC, Ashton KR, Windover AK, Heinberg LJ. Psychological considerations for bariatric surgery among older adults. Obes Surg. 2009;19(2):211-6.
28. Chang CY, Hung CK, Chang YY, Tai CM, Lin JT, Wang JD. Health-related quality of life in adult patients with morbid obesity coming for bariatric surgery. Obes Surg. 2010;20(8):1121-7.
29. Muller MK, Wenger C, Schiesser M, Clavien PA, Weber M.
Quality of life after bariatric surgery--a comparative study of laparoscopic banding vs. bypass. Obes Surg. 2008;18(12):1551-7.
30. Aftab H, Risstad H, Sovik TT, Tomm Bernklev PD, Hewitt S, Kristinsson JA, et al. Five-year outcome after gastric bypass for morbid obesity in a Norwegian cohort. Surg Obes Relat Dis. 2014;10(1):71-8.
31. Sundbom M, Karlson BM. Low mortality in bariatric surgery 1995 through 2005 in Sweden, in spite of a shift to more complex procedures. Obes Surg. 2009;19(12):1697-701.
32. Bult MJ, van Dalen T, Muller AF. Surgical treatment of
obesity. Eur J Endocrinol. 2008;158(2):135-45.
33. Fried M, Yumuk V, Oppert JM, Scopinaro N, Torres A, Weiner R, et al. Interdisciplinary European Guidelines on Metabolic and Bariatric Surgery. Obes Surg.
34. SOReg - Scandinavian Obesity Surgery Register. [Internet]. 2011. Available from: http://www.ucr.uu.se/soreg/.
35. Al-Saif O, Gallagher SF, Banasiak M, Shalhub S, Shapiro D,
Murr MM. Who should be doing laparoscopic bariatric surgery? Obes Surg. 2003;13(1):82-7.
36. Saber AA, Elgamal MH, McLeod MK. Bariatric surgery: the past, present, and future. Obes Surg. 2008;18(1):121-8.
71
37. Kermarrec N, Marmuse JP, Faivre J, Lasocki S, Mognol P, Chosidow D, et al. High mortality rate for patients requiring intensive care after surgical revision following bariatric surgery. Obes Surg. 2008;18(2):171-8.
38. Katkhouda N, Mason RJ, Wu B, Takla FS, Keenan RM,
Zehetner J. Evaluation and treatment of patients with cardiac disease undergoing bariatric surgery. Surg Obes Relat Dis.8(5):634-40.
39. Gugliotti D, Grant P, Jaber W, Aboussouan L, Bae C, Sessler D, et al. Challenges in cardiac risk assessment in bariatric surgery patients. Obes Surg. 2008;18(1):129-33.
40. Capella JF, Capella RF. Bariatric surgery in adolescence. is this the best age to operate? Obes Surg. 2003;13(6):826-32.
41. O'Neill T, Allam J. Anaesthetic considerations and
management of the obese patient presenting for bariatric surgery. Current Anaesthesia & Critical Care. 2010;21(1):16-23.
42. Tsueda K, Debrand M, Zeok SS, Wright BD, Griffin WO. Obesity supine death syndrome: reports of two morbidly obese patients. Anesth Analg. 1979;58(4):345-7.
43. Brodsky JB. Positioning the morbidly obese patient for anesthesia. Obes Surg. 2002;12(6):751-8.
44. Langeron O, Masso E, Huraux C, Guggiari M, Bianchi A,
Coriat P, et al. Prediction of difficult mask ventilation. Anesthesiology. 2000;92(5):1229-36.
45. Adams JP, Murphy PG. Obesity in anaesthesia and intensive care. Br J Anaesth. 2000;85(1):91-108.
46. Coussa M, Proietti S, Schnyder P, Frascarolo P, Suter M, Spahn DR, et al. Prevention of atelectasis formation during the induction of general anesthesia in morbidly obese patients. Anesth Analg. 2004;98(5):1491-5.
47. Casati A, Putzu M. Anesthesia in the obese patient:
pharmacokinetic considerations. J Clin Anesth. 2005;17(2):134-45.
48. Bryson GL, Chung F, Cox RG, Crowe MJ, Fuller J, Henderson C, et al. Patient selection in ambulatory anesthesia - an evidence-based review: part II. Can J Anaesth. 2004;51(8):782-94.
72
49. Nguyen NT, Wolfe BM. The physiologic effects of pneumoperitoneum in the morbidly obese. Ann Surg. 2005;241(2):219-26.
50. Catheline JM, Bihan H, Le Quang T, Sadoun D, Charniot JC,
Onnen I, et al. Preoperative cardiac and pulmonary assessment in bariatric surgery. Obes Surg. 2008;18(3):271-7.
51. Poirier P, Alpert MA, Fleisher LA, Thompson PD, Sugerman HJ, Burke LE, et al. Cardiovascular evaluation and management of severely obese patients undergoing surgery: a science advisory from the American Heart Association. Circulation. 2009;120(1):86-95.
52. Smith TB, Stonell C, Purkayastha S, Paraskevas P. Cardiopulmonary exercise testing as a risk assessment method in non cardio-pulmonary surgery: a systematic review. Anaesthesia. 2009;64(8):883-93.
53. Moretto M, Kupski C, Mottin CC, Repetto G, Garcia Toneto
M, Rizzolli J, et al. Hepatic steatosis in patients undergoing bariatric surgery and its relationship to body mass index and co-morbidities. Obes Surg. 2003;13(4):622-4.
54. Lewis MC, Phillips ML, Slavotinek JP, Kow L, Thompson CH, Toouli J. Change in liver size and fat content after treatment with Optifast very low calorie diet. Obes Surg. 2006;16(6):697-701.
55. Liu R, Sabnis A, Forsyth C, Chand B. The Effects of Acute Preoperative Weight Loss on Laparoscopic Roux-en-Y Gastric Bypass. Obesity Surgery. 2005;15(10):1396-402.
56. Fris R. Preoperative Low Energy Diet Diminishes Liver Size.
Obesity Surgery. 2004;14(9):1165-70.
57. Benotti PN, Still CD, Wood GC, Akmal Y, King H, El Arousy H, et al. Preoperative weight loss before bariatric surgery. Arch Surg. 2009;144(12):1150-5.
58. Alami RS, Morton JM, Schuster R, Lie J, Sanchez BR, Peters A, et al. Is there a benefit to preoperative weight loss in gastric bypass patients? A prospective randomized trial. Surg Obes Relat Dis. 2007;3(2):141-5; discussion 5-6.
59. Alpert MA, Terry BE, Mulekar M, Cohen MV, Massey CV, Fan
TM, et al. Cardiac morphology and left ventricular function in normotensive
73
morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol. 1997;80(6):736-40.
60. Garza CA, Pellikka PA, Somers VK, et al. Structural and
functional changes in left and right ventricles after major weight loss following bariatric surgery for morbid obesity. Am J Cardiol. 2010;105(4):550-6.
61. Syed M, Rosati C, Torosoff MT, El-Hajjar M, Feustel P, Alger S, et al. The impact of weight loss on cardiac structure and function in obese patients. Obes Surg. 2009;19(1):36-40.
62. Hakala K, Maasilta P, Sovijarvi AR. Upright body position and weight loss improve respiratory mechanics and daytime oxygenation in obese patients with obstructive sleep apnoea. Clin Physiol. 2000;20(1):50-5.
63. Pelosi P, Croci M, Ravagnan I, Tredici S, Pedoto A, Lissoni A,
et al. The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. Anesth Analg. 1998;87(3):654-60.
64. Eichenberger A, Proietti S, Wicky S, Frascarolo P, Suter M, Spahn DR, et al. Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem. Anesth Analg. 2002;95(6):1788-92.
65. Damia G, Mascheroni D, Croci M, Tarenzi L. Perioperative changes in functional residual capacity in morbidly obese patients. Br J Anaesth. 1988;60(5):574-8.
66. Reinius H, Jonsson L, Gustafsson S, Sundbom M, Duvernoy
O, Pelosi P, et al. Prevention of atelectasis in morbidly obese patients during general anesthesia and paralysis: a computerized tomography study. Anesthesiology. 2009;111(5):979-87.
67. Hakala K, Mustajoki P, Aittomaki J, Sovijarvi A. Improved gas exchange during exercise after weight loss in morbid obesity. Clin Physiol. 1996;16(3):229-38.
68. Biring MS, Lewis MI, Liu JT, Mohsenifar Z. Pulmonary physiologic changes of morbid obesity. Am J Med Sci. 1999;318(5):293-7.
69. Joris J, Kaba A, Lamy M. Postoperative spirometry after
laparoscopy for lower abdominal or upper abdominal surgical procedures. Br J Anaesth. 1997;79(4):422-6.
74
70. Joris JL, Sottiaux TM, Chiche JD, Desaive CJ, Lamy ML. Effect of bi-level positive airway pressure (BiPAP) nasal ventilation on the postoperative pulmonary restrictive syndrome in obese patients undergoing gastroplasty. Chest. 1997;111(3):665-70.
71. Bergland A, Gislason H, Raeder J. Fast-track surgery for
bariatric laparoscopic gastric bypass with focus on anaesthesia and peri-operative care. Experience with 500 cases. Acta Anaesthesiol Scand. 2008;52(10):1394-9.
72. Malhotra A, Hillman D. Obesity and the lung: 3. Obesity, respiration and intensive care. Thorax. 2008;63(10):925-31.
73. Alpert MA, Chan EJ. Left ventricular morphology and diastolic function in severe obesity: current views. Rev Esp Cardiol. 2012;65(1):1-3.
74. Tavares ID, Sousa AC, Menezes Filho RS, Oliveira MH,
Barreto-Filho JA, Brito AF, et al. Left ventricular diastolic function in morbidly obese patients in the preoperative for bariatric surgery. Arq Bras Cardiol. 2012.
75. Nguyen NT, Anderson JT, Budd M, et al. Effects of pneumoperitoneum on intraoperative pulmonary mechanics and gas exchange during laparoscopic gastric bypass. Surg Endosc. 2004;18(1):64-71.
76. Perilli V, Sollazzi L, Modesti C, et al. Comparison of positive end-expiratory pressure with reverse Trendelenburg position in morbidly obese patients undergoing bariatric surgery: effects on hemodynamics and pulmonary gas exchange. Obes Surg. 2003;13(4):605-9.
77. von Ungern-Sternberg BS, Regli A, Schneider MC, Kunz F,
Reber A. Effect of obesity and site of surgery on perioperative lung volumes. Br J Anaesth. 2004;92(2):202-7.
78. Backer DD, Cholley BP, Slama M, Vieillard-Baron A, Vignon P, editors. Hemodynamic Monitoring Using. Echocardiography in the Critically Ill: Springer-Verlag Berlin Heidelberg; 2011.
79. Jain A, Avendano G, Dharamsey S, Dasmahapatra A, Agarwal R, Reddi A, et al. Left ventricular diastolic function in hypertension and role of plasma glucose and insulin. Comparison with diabetic heart. Circulation. 1996;93(7):1396-402.
75
80. Chen YL, Su MC, Liu WH, Wang CC, Lin MC, Chen MC. Influence and Predicting Variables of Obstructive Sleep Apnea on Cardiac Function and Remodeling in Patients without Congestive Heart Failure. J Clin Sleep Med. 2014;10(1):57-64.
81. Alpert MA. Obesity cardiomyopathy: pathophysiology and
evolution of the clinical syndrome. Am J Med Sci. 2001;321(4):225-36.
82. Banerjee S, Peterson LR. Myocardial metabolism and cardiac performance in obesity and insulin resistance. Curr Cardiol Rep. 2007;9(2):143-9.
83. Movahed MR, Saito Y. Obesity is associated with left atrial enlargement, E/A reversal and left ventricular hypertrophy. Exp Clin Cardiol. 2008;13(2):89-91.
84. Oh JK, Park SJ, Nagueh SF. Established and novel clinical
applications of diastolic function assessment by echocardiography. Circ Cardiovasc Imaging. 2011;4(4):444-55.
85. Jain AK, Dutta A. Stroke volume variation as a guide to fluid administration in morbidly obese patients undergoing laparoscopic bariatric surgery. Obesity Surgery. 2010;20(6):709-15.
86. Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth.105 Suppl 1:i16-23.
87. Collis T, Devereux RB, Roman MJ, de Simone G, Yeh J,
Howard BV, et al. Relations of stroke volume and cardiac output to body composition: the strong heart study. Circulation. 2001;103(6):820-5.
88. Barbosa MM, Beleigoli AM, de Fatima Diniz M, Freire CV, Ribeiro AL, Nunes MC. Strain imaging in morbid obesity: insights into subclinical ventricular dysfunction. Clin Cardiol. 2011;34(5):288-93.
89. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Eur J Heart Fail. 2008;10(10):933-89.
90. Vasan RS, Levy D. Defining diastolic heart failure: a call for
standardized diagnostic criteria. Circulation. 2000;101(17):2118-21.
76
91. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10(2):165-93.
92. Acree LS, Montgomery PS, Gardner AW. The influence of
obesity on arterial compliance in adult men and women. Vasc Med. 2007;12(3):183-8.
93. Ogunnaike BO, Jones SB, Jones DB, Provost D, Whitten CW. Anesthetic considerations for bariatric surgery. Anesth Analg. 2002;95(6):1793-805.
94. Lemmens HJ. Perioperative pharmacology in morbid obesity. Curr Opin Anaesthesiol.23(4):485-91.
95. Janmahasatian S, Duffull SB, Chagnac A, Kirkpatrick CM,
Green B. Lean body mass normalizes the effect of obesity on renal function. Br J Clin Pharmacol. 2008;65(6):964-5.
96. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39(3):215-31.
97. Bellamy JC, Margarson MP. Designing intelligent anesthesia for a changing patient demographic: a consensus statement to provide guidance for specialist and non-specialist anesthetists written by members of and endorsed by the Society for Obesity and Bariatric Anaesthesia (SOBA). Perioperative Medicine 2013;2(12).
98. Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM,
Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051-65.
99. Ingrande J, Brodsky JB, Lemmens HJ. Lean body weight scalar for the anesthetic induction dose of propofol in morbidly obese subjects. Anesth Analg.113(1):57-62.
100. Arain SR, Barth CD, Shankar H, Ebert TJ. Choice of volatile anesthetic for the morbidly obese patient: sevoflurane or desflurane. J Clin Anesth. 2005;17(6):413-9.
101. De Baerdemaeker LE, Struys MM, Jacobs S, Den Blauwen
NM, Bossuyt GR, Pattyn P, et al. Optimization of desflurane administration in morbidly obese patients: a comparison with sevoflurane using an 'inhalation bolus' technique. Br J Anaesth. 2003;91(5):638-50.
77
102. Einarsson S, Bengtsson A, Stenqvist O, Bengtson JP. Decreased respiratory depression during emergence from anesthesia with sevoflurane/N2O than with sevoflurane alone. Can J Anaesth. 1999;46(4):335-41.
103. Patel SS, Goa KL. Sevoflurane. A review of its
pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia. Drugs. 1996;51(4):658-700.
104. Muzi M, Robinson BJ, Ebert TJ, O'Brien TJ. Induction of anesthesia and tracheal intubation with sevoflurane in adults. Anesthesiology. 1996;85(3):536-43.
105. Yurino M, Kimura H. Vital capacity breath technique for rapid anaesthetic induction: comparison of sevoflurane and isoflurane. Anaesthesia. 1992;47(11):946-9.
106. Thwaites A, Edmends S, Smith I. Inhalation induction with
sevoflurane: a double-blind comparison with propofol. British Journal of Anaesthesia. 1997;78(4):356.
107. De Baerdemaeker LE, Jacobs S, Den Blauwen NM, Pattyn P, Herregods LL, Mortier EP, et al. Postoperative results after desflurane or sevoflurane combined with remifentanil in morbidly obese patients. Obes Surg. 2006;16(6):728-33.
108. Tiefenthaler W, Pehboeck D, Hammerle E, Kavakebi P, Benzer A. Lung function after total intravenous anaesthesia or balanced anaesthesia with sevoflurane. Br J Anaesth. 2011;106(2):272-6.
109. Sebel PS, Lowdon JD. Propofol: a new intravenous anesthetic.
Anesthesiology. 1989;71(2):260-77.
110. Atkins JH. Ventilation strategies in gastrointestinal endoscopy. Techniques in gastrointestinal endoscopy. 2009;11:192 - 6.
111. Jensen AG, Callesen T, Hagemo JS, Hreinsson K, Lund V, Nordmark J. Scandinavian clinical practice guidelines on general anaesthesia for emergency situations. Acta Anaesthesiol Scand.54(8):922-50.
112. Tsuchiya M, Yamada T, Asada A. Pleth variability index
predicts hypotension during anesthesia induction. Acta Anaesthesiol Scand. 2010;54(5):596-602.
78
113. Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88(5):1170-82.
114. Conti G, De Cosmo G, Bocci MG, Antonelli M, Ferro G, Costa
R, et al. Alfentanil does not increase resistance of the respiratory system in ASA I patients ventilated mechanically during general anesthesia. Can J Anaesth. 2002;49(7):718-23.
115. Salihoglu Z, Demiroluk S, Demirkiran, Kose Y. Comparison of effects of remifentanil, alfentanil and fentanyl on cardiovascular responses to tracheal intubation in morbidly obese patients. Eur J Anaesthesiol. 2002;19(2):125-8.
116. Roberts GW, Bekker TB, Carlsen HH, Moffatt CH, Slattery PJ, McClure AF. Postoperative nausea and vomiting are strongly influenced by postoperative opioid use in a dose-related manner. Anesth Analg. 2005;101(5):1343-8.
117. De Baerdemaeker LE, Jacobs S, Pattyn P, Mortier EP, Struys
MM. Influence of intraoperative opioid on postoperative pain and pulmonary function after laparoscopic gastric banding: remifentanil TCI vs sufentanil TCI in morbid obesity. Br J Anaesth. 2007;99(3):404-11.
118. Lemmens HJ, Brodsky JB. The dose of succinylcholine in morbid obesity. Anesth Analg. 2006;102(2):438-42.
119. de Leon A, Thorn SE, Wattwil M. High-resolution solid-state manometry of the upper and lower esophageal sphincters during anesthesia induction: a comparison between obese and non-obese patients. Anesth Analg. 2010;111(1):149-53.
120. de Leon A, Thorn SE, Raoof M, Ottosson J, Wattwil M. Effects
of different respiratory maneuvers on esophageal sphincters in obese patients before and during anesthesia. Acta Anaesthesiol Scand. 2010;54(10):1204-9.
121. Gonzalez H, Minville V, Delanoue K, Mazerolles M, Concina D, Fourcade O. The importance of increased neck circumference to intubation difficulties in obese patients. Anesth Analg. 2008;106(4):1132-6, table of contents.
122. Brodsky JB, Lemmens HJ, Brock-Utne JG, Vierra M, Saidman LJ. Morbid obesity and tracheal intubation. Anesth Analg. 2002;94(3):732-6.
79
123. Brodsky JB, Lemmens HJ, Brock-Utne JG, Saidman LJ, Levitan R. Anesthetic considerations for bariatric surgery: proper positioning is important for laryngoscopy. Anesth Analg. 2003;96(6):1841-2; author reply 2.
124. Rao SL, Kunselman AR, Schuler HG, DesHarnais S.
Laryngoscopy and tracheal intubation in the head-elevated position in obese patients: a randomized, controlled, equivalence trial. Anesth Analg. 2008;107(6):1912-8.
125. Collins JS, Lemmens HJ, Brodsky JB, Brock-Utne JG, Levitan RM. Laryngoscopy and morbid obesity: a comparison of the "sniff" and "ramped" positions. Obes Surg. 2004;14(9):1171-5.
126. Dixon BJ, Dixon JB, Carden JR, Burn AJ, Schachter LM, Playfair JM, et al. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology. 2005;102(6):1110-5.
127. Perilli V, Sollazzi L, Bozza P, Modesti C, Chierichini A,
Tacchino RM, et al. The effects of the reverse trendelenburg position on respiratory mechanics and blood gases in morbidly obese patients during bariatric surgery. Anesth Analg. 2000;91(6):1520-5.
128. El-Khatib MF, Kanazi G, Baraka AS. Noninvasive bilevel positive airway pressure for preoxygenation of the critically ill morbidly obese patient. Can J Anaesth. 2007;54(9):744-7.
129. Rapaport S, Joannes-Boyau O, Bazin R, Janvier G. [Comparison of eight deep breaths and tidal volume breathing preoxygenation techniques in morbid obese patients]. Ann Fr Anesth Reanim. 2004;23(12):1155-9.
130. Gander S, Frascarolo P, Suter M, Spahn DR, Magnusson L.
Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients. Anesth Analg. 2005;100(2):580-4.
131. Hedenstierna G, Edmark L, Aherdan KK. Time to reconsider the pre-oxygenation during induction of anaesthesia. Minerva Anestesiol. 2000;66(5):293-6.
132. Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G. Optimal oxygen concentration during induction of general anesthesia. Anesthesiology. 2003;98(1):28-33.
80
133. Abdi W, Dhonneur G, Amathieu R, Adhoum A, Kamoun W, Slavov V, et al. LMA supreme versus facemask ventilation performed by novices: a comparative study in morbidly obese patients showing difficult ventilation predictors. Obes Surg. 2009;19(12):1624-30.
134. Keller C, Brimacombe J, Kleinsasser A, Brimacombe L. The
Laryngeal Mask Airway ProSeal(TM) as a temporary ventilatory device in grossly and morbidly obese patients before laryngoscope-guided tracheal intubation. Anesth Analg. 2002;94(3):737-40.
135. Marrel J, Blanc C, Frascarolo P, Magnusson L. Videolaryngoscopy improves intubation condition in morbidly obese patients. Eur J Anaesthesiol. 2007;24(12):1045-9.
136. Pelosi P, Ravagnan I, Giurati G, Panigada M, Bottino N, Tredici S, et al. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. Anesthesiology. 1999;91(5):1221-31.
137. Perel A, Habicher M, Sander M. Bench-to-bedside review:
Functional hemodynamics during surgery - should it be used for all high-risk cases? Crit Care. 2013;17(1):203.
138. Bundgaard-Nielsen M, Ruhnau B, Secher NH, Kehlet H. Flow-related techniques for preoperative goal-directed fluid optimization. Br J Anaesth. 2007;98(1):38-44.
139. Popescu WM, Schwartz JJ. Perioperative Considerations for the Morbidly Obese Patient. Advances in Anesthesia. 2007;25:59-77.
140. Pinsky MR, Teboul JL. Assessment of indices of preload and
volume responsiveness. Curr Opin Crit Care. 2005;11(3):235-9.
141. Cannesson M. Arterial Pressure Variation and Goal-Directed Fluid Therapy. Journal of Cardiothoracic and Vascular Anesthesia. 2010;24(3):487-97.
142. Slagt C, Breukers RM, Groeneveld AB. Choosing patient-tailored hemodynamic monitoring. Crit Care. 2010;14(2):208.
143. Ramsingh DS, Sanghvi C, Gamboa J, Cannesson M, Applegate
RL, 2nd. Outcome impact of goal directed fluid therapy during high risk abdominal surgery in low to moderate risk patients: a randomized controlled trial. J Clin Monit Comput. 2013;27(3):249-57.
81
144. Alhashemi JA, Cecconi M, Hofer CK. Cardiac output monitoring: an integrative perspective. Crit Care. 2011;15(2):214.
145. Ramsingh D, Alexander B, Cannesson M. Clinical review:
Does it matter which hemodynamic monitoring system is used? Critical Care C7 - 208. 2013;17(2):1-13.
146. Wang P, Wang HW, Zhong TD. Effect of stroke volume variability- guided intraoperative fluid restriction on gastrointestinal functional recovery. Hepatogastroenterology. 2012;59(120):2457-60.
147. Vieillard-Baron A, Charron C, Chergui K, Peyrouset O, Jardin F. Bedside echocardiographic evaluation of hemodynamics in sepsis: is a qualitative evaluation sufficient? Intensive Care Med. 2006;32(10):1547-52.
148. Barbier C, Loubieres Y, Schmit C, Hayon J, Ricome JL, Jardin
F, et al. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med. 2004;30(9):1740-6.
149. Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004;30(9):1834-7.
150. Boyd JH, Walley KR. The role of echocardiography in hemodynamic monitoring. Curr Opin Crit Care. 2009;15(3):239-43.
151. Charron C, Caille V, Jardin F, Vieillard-Baron A.
Echocardiographic measurement of fluid responsiveness. Curr Opin Crit Care. 2006;12(3):249-54.
152. Pinsky MR. Hemodynamic monitoring over the past 10 years. Crit Care. 2006;10(1):117.
153. McLean AS, Huang SJ, Kot M, Rajamani A, Hoyling L. Comparison of cardiac output measurements in critically ill patients: FloTrac/Vigileo vs transthoracic Doppler echocardiography. Anaesth Intensive Care. 2011;39(4):590-8.
154. Canty DJ, Royse CF, Kilpatrick D, Bowman L, Royse AG. The
impact of focused transthoracic echocardiography in the pre-operative clinic. Anaesthesia. 2012;67(6):618-25.
82
155. Manecke GR. Edwards FloTrac sensor and Vigileo monitor: easy, accurate, reliable cardiac output assessment using the arterial pulse wave. Expert Rev Med Devices. 2005;2(5):523-7.
156. Mayer J, Boldt J, Poland R, Peterson A, Manecke GR, Jr.
Continuous arterial pressure waveform-based cardiac output using the FloTrac/Vigileo: a review and meta-analysis. J Cardiothorac Vasc Anesth. 2009;23(3):401-6.
157. Hofer CK, Senn A, Weibel L, Zollinger A. Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac and PiCCOplus system. Crit Care. 2008;12(3):R82.
158. De Backer D, Marx G, Tan A, Junker C, Van Nuffelen M, Huter L, et al. Arterial pressure-based cardiac output monitoring: a multicenter validation of the third-generation software in septic patients. Intensive Care Med.37(2):233-40.
159. Biais M, Vidil L, Sarrabay P, Cottenceau V, Revel P, Sztark F.
Changes in stroke volume induced by passive leg raising in spontaneously breathing patients: comparison between echocardiography and Vigileo/FloTrac device. Crit Care. 2009;13(6):R195.
160. Hoiseth LO, Hoff IE, Myre K, Landsverk SA, Kirkeboen KA. Dynamic variables of fluid responsiveness during pneumoperitoneum and laparoscopic surgery. Acta Anaesthesiol Scand.56(6):777-86.
161. Mayer J, Boldt J, Beschmann R, Stephan A, Suttner S. Uncalibrated Arterial Pressure Waveform Analysis for Cardiac Output Determination in Obese Patients. Anesthesiology. 2008;109(A1491):A1491.
162. Raghunathan K, Bloomstone JA, McGee WT. Cardiac output
measured with both esophageal Doppler device and Vigileo-FloTrac device. Anesth Analg. 2012;114(5):1141-2; author reply 2.
163. Meng L, Tran NP, Alexander BS, Laning K, Chen G, Kain ZN, et al. The impact of phenylephrine, ephedrine, and increased preload on third-generation Vigileo-FloTrac and esophageal doppler cardiac output measurements. Anesth Analg.113(4):751-7.
164. Lambert DM, Marceau S, Forse RA. Intra-abdominal pressure in the morbidly obese. Obes Surg. 2005;15(9):1225-32.
165. Sugerman HJ. Effects of increased intra-abdominal pressure
in severe obesity. Surg Clin North Am. 2001;81(5):1063-75.
83
166. Kirkpatrick AW, Roberts DJ, De Waele J, et al. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med. 2013;39(7):1190-206.
167. Vivier E, Metton O, Piriou V, Lhuillier F, Cottet-Emard JM,
Branche P, et al. Effects of increased intra-abdominal pressure on central circulation. Br J Anaesth. 2006;96(6):701-7.
168. Chandrakantan A, Glass PS. Multimodal therapies for postoperative nausea and vomiting, and pain. Br J Anaesth. 2011;107 Suppl 1:i27-40.
169. Petersen PL, Mathiesen O, Torup H, Dahl JB. The transversus abdominis plane block: a valuable option for postoperative analgesia? A topical review. Acta Anaesthesiol Scand. 2010;54(5):529-35.
170. Kasner M, Gaub R, Westermann D, et al. Simultaneous
estimation of NT-proBNP on top to mitral flow Doppler echocardiography as an accurate strategy to diagnose diastolic dysfunction in HFNEF. Int J Cardiol. 2011;149(1):23-9.
171. Pfister R, Schneider CA. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: application of natriuretic peptides. Eur Heart J. 2009;30(3):382-3; author reply 3.
172. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350(7):655-63.
173. Muzi M, Colinco MD, Robinson BJ, Ebert TJ. The effects of
premedication on inhaled induction of anesthesia with sevoflurane. Anesth Analg. 1997;85(5):1143-8.
174. Lavazais S, Debaene B. Choice of the hypnotic and the opioid for rapid-sequence induction. Eur J Anaesthesiol Suppl. 2001;23:66-70.
175. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22(2):107-33.
176. Rudski LG, Lai WW, Afilalo J, et al. Guidelines for the
echocardiographic assessment of the right heart in adults. J Am Soc Echocardiogr. 2010;23(7):685-713.
84
177. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification. J Am Soc Echocardiogr. 2005;18(12):1440-63.
178. Brennan JM, Blair JE, Goonewardena S, Ronan A, Shah D,
Vasaiwala S, et al. Reappraisal of the use of inferior vena cava for estimating right atrial pressure. J Am Soc Echocardiogr. 2007;20(7):857-61.
179. Kircher BJ, Himelman RB, Schiller NB. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol. 1990;66(4):493-6.
180. Beaulieu Y, Marik PE. Bedside ultrasonography in the ICU: part 1. Chest. 2005;128(2):881-95.
181. Goonewardena SN, Blair JE, Manuchehry A, Brennan JM,
Keller M, Reeves R, et al. Use of hand carried ultrasound, B-type natriuretic peptide, and clinical assessment in identifying abnormal left ventricular filling pressures in patients referred for right heart catheterization. J Card Fail. 2010;16(1):69-75.
182. Blair JE, Brennan JM, Goonewardena SN, Shah D, Vasaiwala S, Spencer KT. Usefulness of hand-carried ultrasound to predict elevated left ventricular filling pressure. Am J Cardiol. 2009;103(2):246-7.
183. Jensen MB, Sloth E, Larsen KM, Schmidt MB. Transthoracic echocardiography for cardiopulmonary monitoring in intensive care. Eur J Anaesthesiol. 2004;21(9):700-7.
184. Vincent JL. Understanding cardiac output. Crit Care.
2008;12(4):174.
185. Bundgaard-Nielsen M, Jorgensen CC, Secher NH, Kehlet H. Functional intravascular volume deficit in patients before surgery. Acta Anaesthesiol Scand.54(4):464-9.
186. Feissel M, Michard F, Mangin I, Ruyer O, Faller JP, Teboul JL. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest. 2001;119(3):867-73.
187. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson
PW, et al. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004;109(5):594-600.
85
188. Mayer J, Boldt J, Beschmann R, Stephan A, Suttner S. Individualized intraoperative patient optimization using uncalibrated arterial pressure waveform analysis in high-risk patients undergoing major abdominal surgery. Critical Care. 2009;13(Suppl 1):P219.
189. Jones RM, Moulton CE, Hardy KJ. Central venous pressure
and its effect on blood loss during liver resection. Br J Surg. 1998;85(8):1058-60.
190. Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative fluid management. Anesthesiology. 2008;109(4):723-40.
191. Bundgaard-Nielsen M, Secher NH, Kehlet H. 'Liberal' vs. 'restrictive' perioperative fluid therapy--a critical assessment of the evidence. Acta Anaesthesiol Scand. 2009;53(7):843-51.
192. Iijima T. Complexity of blood volume control system and its
implications in perioperative fluid management. J Anesth. 2009;23(4):534-42.
193. Bundgaard-Nielsen M, Holte K, Secher NH, Kehlet H. Monitoring of peri-operative fluid administration by individualized goal-directed therapy. Acta Anaesthesiol Scand. 2007;51(3):331-40.
194. Borup T, Hahn RG, Holte K, Ravn L, Kehlet H. Intra-operative colloid administration increases the clearance of a post-operative fluid load. Acta Anaesthesiol Scand. 2009;53(3):311-7.
195. Hartog CS, Kohl M, Reinhart K. A systematic review of third-
generation hydroxyethyl starch (HES 130/0.4) in resuscitation: safety not adequately addressed. Anesth Analg.112(3):635-45.
196. White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg. 2005;101(5 Suppl):S5-22.
197. Sollazzi L, Modesti C, Vitale F, Sacco T, Ciocchetti P, Idra AS, et al. Preinductive use of clonidine and ketamine improves recovery and reduces postoperative pain after bariatric surgery. Surg Obes Relat Dis. 2009;5(1):67-71.
198. Dikmen Y, Eminoglu E, Salihoglu Z, Demiroluk S. Pulmonary
mechanics during isoflurane, sevoflurane and desflurane anaesthesia. Anaesthesia. 2003;58(8):745-8.
86
199. Salihoglu Z, Demiroluk S, Dikmen Y. Respiratory mechanics in morbid obese patients with chronic obstructive pulmonary disease and hypertension during pneumoperitoneum. Eur J Anaesthesiol. 2003;20(8):658-61.
200. Landoni G, Fochi O, Torri G. Cardiac protection by volatile
anaesthetics: a review. Current vascular pharmacology. 2008;6(2):108-11.
201. Kojima A, Kitagawa H, Omatsu-Kanbe M, Matsuura H, Nosaka S. Sevoflurane protects ventricular myocytes against oxidative stress-induced cellular Ca2+ overload and hypercontracture. Anesthesiology. 2013;119(3):606-20.
202. Lopez-Alvarez S, Mayo-Moldes M, Zaballos M, Iglesias BG, Blanco-Davila R. Esmolol versus ketamine-remifentanil combination for early postoperative analgesia after laparoscopic cholecystectomy: a randomized controlled trial. Can J Anaesth. 2012;59(5):442-8.
203. Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in
anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth. 2004;93(6):799-805.
204. Feng CK, Chan KH, Liu KN, et al. A comparison of lidocaine, fentanyl, and esmolol for attenuation of cardiovascular response to laryngoscopy and tracheal intubation. Acta Anaesthesiol Sin. 1996;34(2):61-7.
205. Hui TW, Short TG, Hong W, Suen T, Gin T, Plummer J. Additive interactions between propofol and ketamine when used for anesthesia induction in female patients. Anesthesiology. 1995;82(3):641-8.
206. Min JH, Chai HS, Kim YH, et al. Attenuation of hemodynamic
responses to laryngoscopy and tracheal intubation during rapid sequence induction: remifentanil vs. lidocaine with esmolol. Minerva Anestesiol. 2010;76(3):188-92.
207. Jean J, Compere V, Fourdrinier V, Marguerite C, Auquit-Auckbur I, Milliez PY, et al. The risk of pulmonary aspiration in patients after weight loss due to bariatric surgery. Anesth Analg. 2008;107(4):1257-9.
