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Acta Anaesthesiol Scand 2009; 53: 843–851 r 2009 The Authors

Printed in Singapore. All rights reserved Journal compilation r 2009 The Acta Anaesthesiologica Scandinavica Foundation

ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2009.02029.x

Review Article

‘Liberal’ vs. ‘restrictive’ perioperative fluid therapy – a
critical assessment of the evidence
M. BUNDGAARD-NIELSEN1,2, N. H. SECHER2 and H. KEHLET1
1
Section of Surgical Pathophysiology, and 2Department of Anaesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Background: Several studies have assessed the effect of a regimen whereas two studies found no difference and two
‘liberal’ vs. a ‘restrictive’ perioperative fluid regimen on studies found differences in the selected outcome para-
post-operative outcome. The literature was reviewed in meters.
order to provide recommendations regarding periopera- Conclusion: Liberal vs. restrictive fixed-volume regimens
tive fluid regimens. are not well defined in the literature regarding the defini-
Methods: A PubMed search identified randomized clinical tion, methodology and results, and lack the use of or
trials and cited studies, comparing two different fixed fluid information on evidence-based standardized periopera-
volumes on post-operative clinical outcome in major surgery. tive care-principles (fast-track surgery), thereby preclud-
Studies were assessed for the type of surgery, primary and ing evidence-based guidelines for procedure-specific
secondary outcome endpoints, the type and volume of admi- perioperative fixed-volume regimens. Optimization of
nistered fluid and the definition of the perioperative period. perioperative fluid management may include a combina-
Also, information regarding perioperative care and type of tion of fixed crystalloid administration to replace extra-
anaesthesia was assessed. vascular losses and avoiding fluid excess, together with
Results: In the seven randomized studies identified, the individualized goal-directed colloid administration to
range of the liberal intraoperative fluid regimen was from maintain a maximal stroke volume.
2750 to 5388 ml compared with 998 to 2740 ml for the
restrictive fluid regimen. The period for fluid therapy
and outcome endpoints were inconsistently defined and
Accepted for publication 24 April 2009
only two studies reported perioperative care principles
and discharge criteria. Three studies found an improved r 2009 The Authors
outcome (morbidity/hospital stay) with a restrictive fluid Journal compilation r 2009 The Acta Anaesthesiologica Scandinavica Foundation

F LUID administration is an integrated part of care
for almost any surgical procedure and conse-
quently an everyday issue for most anaesthesiolo-
outcome. Attention has been directed towards
different volume regimens referred to as ‘liberal’
or ‘high’ vs. ‘restricted’ or ‘low’. In minor ambula-
gists. Perioperative fluid therapy has received tory/semi ambulatory procedures, more than 18
increased interest in recent years because several randomized trials have investigated the effect of
studies have demonstrated that the strategy for administering more or o than  1 l of fluid and
fluid therapy may influence the post-operative conclude that more than 1 l of crystalloid results in
outcome.1–6 Obviously, hypovolaemia is recog- reduction of symptoms related to dehydration.2,4,7
nized as a risk factor leading to adverse effects However, the data comparing crystalloid regimens
ranging from minor organ dysfunction to multi- in major procedures have not provided similar
organ failure and even death. Conversely, liberal clear recommendations.
administration of fluid may impair pulmonary, Therefore, the purpose of this review was to
cardiac and gastro-intestinal functions, contribut- assess the randomized trials comparing a liberal
ing to post-operative complications and prolonged vs. a restricted fixed-volume crystalloid regimen
recovery.1,4,6 Yet, with no established definition of in major surgery in order to establish information
normovolaemia, it has been difficult to monitor for clinical practice and guidelines for future
how much volume is required to ensure an optimal studies.

843

lost fluid. different periods were reported arthroplasty.2 l in A PubMed search identified randomized clinical the restricted group at day 48 and 2.11. discharge were evaluated. trointestinal function.12 gastric emptying time.10 Post-operatively. Finally.14 tration and then only in the liberal groups (Table intravenous fluids were not provided post-opera- 2).11. In the study by Brandstrup with patients 418 years in the period 1966–2008.10 blood Studies were assessed for information regarding products were provided. et al.10. period. the type and volume of administered and colloid of 7 mg/kg was given.11. Kabon et al. Five studies provided additional fluid besides the mized human studies published in English and fixed-volume regimen. More- two studies by Holte et al. and additional blood loss was replaced with additional Analysis HAES. In the study by MacKay et al.14 but only on fluid intake/administration vs. a restrictive tively and fluid needs were managed by oral intraoperative fluid regimen differed between stu. ranging from ‘intraoperative’8 to ‘intraoperative gery included colorectal procedures8–12 or a variety including PACU stay’11 to ‘day of operation’10. type of anaesthesia and the use of was transfused with a haematocrit o24% (o30% in epidural analgesia was assessed. intake. blood loss.10 ‘Liberal’ vs.8 In the fast-track studies by Holte et al. In one 2900 ml in the liberal group and between 500 and study. Outcome endpoints 1). the tions9. The post-opera- tive period was defined from 1 h post-operatively12 ‘to midnight’8or as the first post-operative day. Consequently.13 and death13 were used in six studies as studies reported a volume that ranged from 1500 to the primary outcome parameters (Table 1). ‘restrictive’ fluid regimen One study primarily evaluated the post-operative Two studies reported pre-operative fluid adminis. Search terms ‘fluid therapy’ and Indications for additional fluid administration ‘outcome’ were combined and limited to rando.13 a definition of the perioperative period were regis- CVPo15 mmHg was an indication of colloid ad- tered. no indication the type of surgery.11. gastrointestinal recovery was 844 .12 The definition of a liberal vs. Additional studies were identified from synthetic colloid (HAES 6%) 1 : 1 according to review articles and papers cited in original papers. From the 187 identified studies.14 a fixed volume of over. however.13.9. and blood management. of abdominal procedures. the post-operative period strategy (Table 1).. weight before and after surgery and the In the study by Nisanevich et al. fluid losses ex.14 Finally.M. the liberal group received 1000– 1500 ml of saline with a blood loss  500 ml.vs. Methods Only two of these studies reported a conventional fluid balance of 3. When assessing the fluid volume administered dominal surgery8–13 and one study included knee intraoperatively.9. Six studies included major ab.14 teria.10 Five studies reported ported in four studies. patients with cardiac morbidity). information regarding perioperative ministration or pharmacologic support.7 l in the liberal group and 0.3 l in the liberal trials comparing the effect of two different fixed group and 1.14 fluid volumes on one or more post-operative clin- ical outcome parameters in adults undergoing major surgery. post.10. The range of a liberal intraoperative fluid regimen was from 2750 to 5388 ml compared with 998 to 2740 ml for the restrictive fluid regimen (Fig.2 l in the restricted group at day 0. complications and fitness for operative volume administration was only re. Five studies provided data length of hospital stay (LOS).14 Studies addressing abdominal sur. three studies reported well-defined discharge cri- pressed as a change in body weight (Table 2).12 provided additional fluid if diuresis waso1 ml/ Results kg/h or if MAPo70% of preinduction. a restrictive fluid regimen in one Wound infection.11.8 pul- study9 differed only 10 ml from what was defined monary function. dies. the restricted group was provided with a May 22. However. only seven rando- mized studies were selected according to the search The intra.14 post-operative complica- as liberal in another trial.9. no primary endpoint was defined but gas- 2170 ml in the restricted group.8. Bundgaard-Nielsen et al. number of patients and pri- of these or other colloid products was given.13 which was not further specified. In the mary and secondary outcome endpoints.8–11.

dizzy/drowsiness. ! . decreased/reduced. nausea. increased/improved. gastro-intestinal. High. LOS (High 9 days. appetite. i.: thio/ Wound ! Wound infection resection/253 fentanyl. fatigue.. Blinding Epi Epi Anaesthesia Outcome Result pt (n) III/IV (%) track intraop post-op Lobo8 2002 Hemi – No No No No – Gastric Low: " GI recovery colectomy/20 emptying time # LOS: High 9 days. # . propofol. Table 1 Perioperative methodology and result of fixed volume randomized trials. pain. low 6 days Brandstrup9 Colorectal 47/51/2/0 No Assessor Yes Yes – Complications Low: # complications 2003 resection/141 Kabon12 2005 Colon 10/75/15/0 No – – – i. prop. Low. ! death Mackay10 2006 Colorectal 5/70/24/1 No Assessor – – – Recovery ! GI recovery. headache.v. low 8 days). remifentanil. vola: complications " GI recovery iso/NO # complications.2 resection/69 days). intravenous. LOS Holte11 2007 Colonic 22/25/53/0 No Double Yes Yes i.v.: prop/ Physiological High: surgery/32 remi recovery # pulmonary function. remi. pulmonary function ! exercise capacity. low fluid regimen. GI. well-being. thirst. ileus. ileus. vasoactive hormones. ‘restrictive’ perioperative fluid therapy 845 . total complications ! exercise capacity. pain. volatile anaesthetic.v. no change. Study and year Procedure/ ASA I/II/ Fast. high fluid regimen.v. vola: infection iso/NO Nisanevich13 Major abdominal 22/52/26/0 Yes Assessor No Yes i. post-op hypoxaemia. ‘Liberal’ vs. LOS " . vola. fatigue. LOS (7. complications Holte14 2007 Arthroplasty/48 29/48/23/0 Yes Double Yes Yes Epi/spinal Perioperative High: physiology and # vomiting organ function " coagulation.: thio/ Death and Low: 2005 surgery/142 fentanyl. well-being.

disseminated et al. the two trials reporting LOS did not evidence-based care principles including pre-opera- define any criteria for discharge.2 2 . Post-operative period as defined in Table 2.13 one study was not blinded. inflammatory bowel dis. impaired mobility.13 One study did not regimen. or gastro-intestinal recovery and LOS (7. Two studies were assessor blinded. congestive between the liberal and the restrictive fluid regi- cardiac failure.9. Intraoperative and post-operative administered fluid volume in randomized trials comparing ‘high’ vs. ASA ranged from I to III (18%). pregnancy. ta a al al al al al al et Ka p et et e et et et et et et et et bo p bo lte n h h y on lte y tru Ka bo vic Lo Lo Ho Ho b ds ds Ka ac ac ne ne an an M M sa sa Br Br Ni Ni Fig. post-operatively. tru al. Patients with fever. alcohol consumption 435 U/week. cancer. of which one study dural and systemic analgesia.9 In the Studies with no difference in outcome (Table 2).9. Two studies reported additional use of colloid the three studies recommending a restrictive fluid (HAES 6%.12 For MacKay et al.9 (Table oral nutrition.14 omy. ‘low’ fluid regimens.9 In the study by Nisanevich et al. ary oedema were excluded in the study by Kabon betes mellitus. use Lobo et al. vic al.13 studies in colonic surgery showed no difference Patients with impaired renal function.M. men with outcome expressed as wound infection12 ascites.13 hepatect- outcome variables in two studies.2 . ‘low’ volume regimen. Intraoperative Postoperative 6000 6000 5000 5000 Volume (ml) 4000 4000 3000 3000 2000 2000 1000 1000 0 0 7 11 28 5 12 39 3 3 6 10 5 12 7 14 39 6 10 02 8 05 1 05 1 00 00 00 00 00 00 0 00 00 20 20 20 0 . early post-operative mobilization and studies used saline and dextrose/glucose8.13 provide ASA classes8 and one study included only a small number of ASA III patients (2%). Bundgaard-Nielsen et al.. ‘high’ volume regimen. renal failure and a history of pulmon- disorders.8. coagulopathy. HES 200/0. Three of seven studies found that epidural analgesia both intra. renal or hepatic dysfunction and congestive heart failure were the exclusion criteria. with two studies show. Black bar. tive information. reported in one trial13 and a battery of physiologi. secondary cancer.2 l.2 2 .13 All three stu. provided with regard to the site (thoracic vs. Grey bar. no information was ing improved gastro-intestinal recovery and a re.11. avoidance of bowel used a balanced solution (Ringers lactate)13 and two preparation.13 However.8 Updated perioperative However. infection. 846 . renal insufficiency.2 days). Two remaining study.9. insu- ease or disease hindering epidural analgesia were lin-dependent diabetes mellitus.2 . mental of diuretics. lactation. lum- duced LOS from 9 to 6 days8 and from 9 to 8 days.2 . total colectomy. hepatic disease.5). optimized opioid-reduced epi- dies reported use of crystalloid. physical disability requiring long-term care.15–17 were not described in any of 2). 1.13 and reduced incidence of complications (Table 1).8.8 whereas pregnancy. diabetes mellitus. peritoneal metastasis. age o18 years. susceptibility to ma- testinal mobility were excluded in the study by lignant hyperthermia. Outcome result One study reported that epidural analgesia was Studies with improved outcome following a restricted fluid not used perioperatively8 and one study used regimen (Table 2).9. the exclusion criteria in the study by Brandstrup cal recovery variables was utilized as secondary et al. congestive heart failure.and post-operatively9 a restrictive fluid regimen improved outcome after and the last study only used epidural analgesia major abdominal surgery.10 anaemia or those taking drugs affecting gastroin.10 renal impairment. bar) or the dose/composition of the epidural regi- respectively. dia.2 .13 Two studies also showed an overall men. Ka al. al l .

high volume group.8 0. Colloid vol.6 RL RL HES Holte11 – – Intra1 5050 1640 3900 1140 500 500 0 0 305 200 1150 700 – – – – – – – 2. low volume group. HES.6 midnight op day S1G S1G HAES HAES Kabon12 700 0 Intra – – 3900 2500 – – – – 322 333 490 310 1 h post-op – – 1100 600 – – – – – – Nisanevich13 – – Intra 3878 1408 – – – – – – 440 400 – – 24 h 2012 2170 – – – – – – RL RL HAES HAES Mackay10 – – Day 2750 2000 2750 2000 – – – – – – – – Day 1 2600 2000 2600 2000 – – 1. Table 2 Perioperative fluid administration and losses in millilitres. post-operative. Post. HAES.4.1  0. Post-op. Cryst.6 S1D S1D Brandstrup9 500 0 To 5388 2740 – – – – – – 500 400 – – First post. no information.5 of OP post-op S1D S1D 14 Holte – – Intra 4250 1740 3275 815 500 500 0 0 0 0 – – – – – – – – – 2. Blood Blood Diuresis Definition All Cryst Diuresis Weight gain type type loss kg/24 h H L H L H L H L H L H L H L H L H L H L Lobo8 – – Intra 2800 2500 2800 2500 0 0 0 0 238 275 1190 776 To midnight 2900 600 2900 600 1190 1741 2. S1D.6 0. RL. H. OP. definition of period. intraoperative. operation.1 0. hydroxyl ethyl starch 130/0. All. saline and glucose. ‘Liberal’ vs. all administered volume. S1G. Definition. 1500 500 – – – – 2. Intra. ringeŕs lactate. crystalloid. post-anaesthetic care unit. post-operative.0 0. ‘restrictive’ perioperative fluid therapy 847 . Study Pre Intra Post H L Definition All Cryst vol.2 PACU RL RL HES Pre. saline and dextrose. PACU. hydroxyl ethyl starch 200/0. –. L. pre-operative.5.

Inconsistent outcome results and study designs tion and oral nutrition were not described in the have been reported with the use of a liberal vs. dated perioperative evidence-based care principles section requiring a defunctioning stoma were the including pre-operative information. the studies suggest formed consent were the exclusion criteria.11. nausea. well-de- was not reported. The majority of identified studies.14 did not describe perio- 2. Both studies reported the use of opioids-reduced analgesia. headache. and to the defined colonic surgery11 showed benefit from a restrictive intra.11 In addition. insu. opti- mized opioid-reduced analgesia. restrictive fluid regimens. im. In exclusion criteria for participation. additional exclusion criteria post-operative outcome. tion by a liberal fluid regimen leading to a weight one. abdominoperineal resection and low-anterior re. NYHA class IV or volume fluid regimen. ance of bowel preparation. in two studies. the study by Brandstrup between groups in exercise capacity. thirst. principles ercise-capacity. age o50 years. a two studies without a difference in outcome. pain.14 The study in colonic represent the general population undergoing color- surgery found an improvement in pulmonary ectal resection. weight were reported in most studies. BMI440. restrictive when referring to the size of a fixed- lin-dependent diabetes mellitus. fatigue. Both studies used a balanced crystalloid detail. were inflammatory bowel disease. optimized non-opioid analgesia. early post-operative mobilization study (saline and dextrose). ASA IV. Nevertheless.5 days. information. avoidance of bowel crystalloid but the type was only stated in one preparation. ileus and LOS (‘high’: double-blinded studies. gain suggests that fluid excess should be avoided. Although changes in body MIo3 month. Study design ment and morphine intolerance were also the Exclusion criteria were extensive in most trials.10 The use of colloid and oral nutrition. ileus. practice. direct comparison and interpretation. but no difference population. a contraindication to tranexa- mic acid/epidural catheter. except for the two dizzy/drowsiness. glucocorticoid and tionally calculated fluid balance was only provided anticoagulant therapy or inability to provide in. Also. Accordingly. This is unfortunate because pre-operative (Ringer’s lactate) and a colloid (HES 140/0.9 only included a limited number of ASA III appetite. renin and AT-II concentration) on administer.M. we consider that the patients included proved pulmonary function and enhanced coagu. post-operative patients (ASA I/II/III: 47/51/2%) and did not hypoxaemia or LOS (4 days). blinded studies regarding knee arthroplasty14 and indications for additional fluid. chronic opioid treat. These inconsistencies re- late both to the amount of administered fluid Studies with differences in outcome (Table 2). avoid- both studies were double-blinded and with up.15–17 In both studies. Details regarding anaesthesia scribed epidural anaesthesia was used intra. et al. a conven- cohol consumption 45 U/day. avoidance of Discussion bowel preparation. inability to perform it is recommended to abandon the terms liberal and the pre-operative test programme. pain.12 and post-operatively and the type of general anaesthe- information on epidural analgesia was not given. ‘low’: 3 days) were not different perative care principles and discharge criteria in (P 5 0. nausea. Bundgaard-Nielsen et al. For both studies. well-being.52). early post-operative mobiliza.01). optimized exclusion criteria. fatigue. In the that the perioperative crystalloid excess impairs the colonic surgery study. psychiatric disorder. the worse outcome function and post-operative hypoxaemia and a demonstrated by this relatively ‘healthy’ popula- reduced vasoactive hormonal response (aldoster.08). ing a liberal fluid regimen. al. need to be representative for the procedure-specific lation with the liberal regimen.4). sia was provided in the colonic surgery study. the number of patients with complications was not Standardized evidence-based perioperative care significantly reduced (P 5 0. weight 4110 kg. Nevertheless. Although the total number of complications was reduced (Po0.and post-operative period as well as infor- or a liberal fluid regimen in different functional mation on perioperative care principles hindering parameters. and in the knee arthroplasty study. Updated perioperative evidence-based care princi- ples including pre-operative information. FEV1o1 l. In this context.and were only provided in one of the studies. The study in order to apply the study findings to daily clinical knee arthroplasty found reduced vomiting. ex. early post-operative mo- 848 . The two volume in the liberal vs. restrictive fluid regimen.

24 and may. The LOS depends on multiple factors and ted concept.25 Thus.13 A reduction in post- operative surgical complications is a tempting Conclusion evaluation of the benefit of one fluid regimen It is of concern that the literature pertaining to a over another. in studies addressing the principles (fast-track surgery). and advocating a restrictive fluid regimen did not describe discharge criteria. Therefore.and intravascular fluid compartments. needs to be examined in procedure-specific studies However.19 Therefore. be defined and evidence-based care principles gender and age are likely to influence the fluid should be adopted in order to evaluate the effect of needs. an approach is to combine the two when precise discharge criteria are not defined. 2). it come in the context of exercise capacity. the role of inconsistent regarding the definitions. mia for every patient (Fig. perioperative death is a rare concept.4 The same applies to semi.7 perioperative fluid therapy could also include a tailored individualized treatment optimizing the intravascular volume by providing maximization of cardiac stroke volume with colloid boluses. it would be of interest to dence-based guidelines for optimal procedure-spe- evaluate functional outcome variables with a cific perioperative fixed-volume regimens cannot known or at least theoretically assumed relation- be formulated.9 Therefore. prevent hypovolaemia and the risk of hypervolae- ambulatory procedures where application of evi.13 while ‘normovolaemia’. we consider that such an approach crystalloid vs. in contrast able require large sample sizes.4 agement may include a combination of fixed crys- talloid administration to replace extra-vascular losses and individualized goal-directed colloid ad- Type of fluid ministration to maintain a maximal cardiac stroke The relative role of the optimal administration of volume.18 surgery applying the ‘fast-track’ methodology had a median hospital stay of  3 days in both groups11 in contrast to the studies reporting a reduction in LOS Clinical and research strategies from 9 to 6 days8 and 9 to 8 days13 with a ‘restricted’ Because differences in surgical trauma.g. balance should be used as a background fluid regimen to function. co-morbidity. a fixed-volume regimen is unlikely to both fluid management per se. ‘Liberal’ vs.9 A more rational strategy for with the restricted regimen. methodol- fluid management in urinary tract infections may ogy and defined outcome parameters. Thus. fine optimal perioperative fluid management. Rational perioperative fluid man- ship with the amount of fluid administration. ‘restrictive’ perioperative fluid therapy bilization and oral nutrition improve post-operative saline should be avoided because they induce outcome per se. the study in abdominal hyperchloraemic acidosis. probably reflecting functional hypovolaemia ing bodyweight. anaesthetic technique. there is evidence favouring balanced combined with evidence-based principles for peri- solutions with an electrolyte concentration similar operative care (fast-track surgery) in order to de- to that found in plasma and large volumes of e. a restrictive fixed-volume regimen is cation is related to fluid therapy. the extra. Yet. when exact criteria for use and studies are hampered by the lack of information on removal of a urinary bladder catheter are not evidence-based standardized perioperative care provided. Thus.23.8. perioperative care needs to tive hydration. offer a definition of used death as a primary outcome variable. rather than choosing LOS has been widely used as a secondary outcome between a fixed-volume regimen and a goal-direc- variable. and most be questioned. provided that the registered compli- liberal vs. Consequently.20. thirst. rather dence-based perioperative care and a liberal fluid than using a fixed volume of crystalloids as the regimen ( 3 l) improved the post-operative out. the Outcome parameters so-called individualized ‘goal-directed therapy’ In elective surgery. colloid ratio has not been resolved.15–17 Thus. dizzy/drowsiness and the hormonal replace extra-vascular fluid losses and with a focus stress response compared with a restricted regimen on avoiding undesirable fluid excess and maintain- ( 1 l).20–22 This strategy has improved outcome event and studies with death as an outcome vari. evi- role of fluid therapy. re- two studies using LOS as an outcome parameter spectively. Only one study to the fixed-volume regimens. pre-opera- regimen. strategies because they replace losses from the interpretation of LOS remains elusive. in 10 randomized trials20. main strategy of perioperative volume handling.26 849 .

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