ORIGINAL ARTICLE

Liberal Versus Restrictive Fluid Administration to Improve

Recovery After Laparoscopic Cholecystectomy
A Randomized, Double-Blind Study
Kathrine Holte, MD,* Birthe Klarskov, RN,* Dorte Stig Christensen, MD,† Claus Lund, MD, PhD,†
Kristine Grubbe Nielsen, MS,* Peter Bie, MD, PhD,‡ and Henrik Kehlet, MD, PhD*

Objective: The objective of this study was to investigate the effects

of 2 levels of intraoperative fluid administration on perioperative L imited scientific evidence on optimal intraoperative fluid
management has resulted in large variations of adminis-
tered fluid regimens in daily practice. Currently, there is a
physiology and outcome after laparoscopic cholecystectomy.
Summary Background Data: Intraoperative fluid administration is tendency toward liberal perioperative fluid administration,1
variable as a result of limited knowledge of physiological and and in laparoscopic cholecystectomy, administration of 1 to 4
clinical effects of different fluid substitution regimens. L of crystalloid has been reported.1 The stress response to
Methods: In a double-blind study, 48 ASA I–II patients undergoing surgery profoundly alters fluid homeostasis leading to fluid
laparoscopic cholecystectomy were randomized to 15 mL/kg (group conservation. Primary mediators are aldosterone, antidiuretic
1) or 40 mL/kg (group 2) intraoperative administration of lactated hormone, and the renin–angiotensin system. However, the
Ringer’s solution (LR). All other aspects of perioperative manage- effect of different fluid regimens on these hormonal responses
ment as well as preoperative fluid status were standardized. Primary
to surgery is largely unknown.1 Although perioperative ad-
outcome parameters were assessed repeatedly for the first 24 post-
operative hours and included pulmonary function (spirometry), ex-
ministration of high volumes may be deleterious in connec-
ercise capacity (submaximal treadmill test), cardiovascular hor- tion with major surgical procedures,1,2 studies in minor (am-
monal responses, balance function, pain, nausea and vomiting, bulatory) surgery suggest that fluid substitution aiming to
recovery, and hospital stay. correct preoperative dehydration may improve some param-
Results: Intraoperative administration of 40 mL/kg compared with eters of recovery (drowsiness and dizziness).3
15 mL/kg LR led to significant improvements in postoperative We therefore investigated the effects of intraoperative
pulmonary function and exercise capacity and a reduced stress fluid administration with 2 different volumes of Ringer’s
response (aldosterone, antidiuretic hormone, and angiotensin II). lactate (LR) (40 mL/kg and 15 mL/kg) for laparoscopic
Nausea, general well-being, thirst, dizziness, drowsiness, fatigue, cholecystectomy on pulmonary function, exercise capacity,
and balance function were also significantly improved, as well as stress responses (aldosterone, antidiuretic hormone 关ADH兴,
significantly more patients fulfilled discharge criteria and were dis-
angiotensin II, atrial natriuretic peptide 关ANP兴, and renin),
charged on the day of surgery with the high-volume fluid substitution.
Conclusions: Intraoperative administration of 40 mL/kg compared
and balance function as the primary outcome assessments.
with 15 mL/kg LR improves postoperative organ functions and recov- Furthermore, pain, nausea, vomiting, hospital stay, and re-
ery and shortens hospital stay after laparoscopic cholecystectomy. covery were assessed.
(Ann Surg 2004;240: 892– 899)
METHODS
In a randomized, double-blind trial, we studied 48
From the *Departments of *Surgical Gastroenterology and †Anesthesiology, consecutive patients scheduled for elective laparoscopic cho-
Hvidovre University Hospital, Hvidovre, Denmark; and the ‡Department lecystectomy from October 23, 2001, to August 20, 2002.
of Physiology and Pharmacology, University of Southern Denmark,
Odense, Denmark. Exclusion criteria were: weight ⬎100 kg; age ⬎70 or ⬍18
The study was supported by grants from the University of Copenhagen and years; pregnancy or lactation; ongoing infection (elevated
the Danish Research Council (no. 22-01-0160). C-reactive protein); inability to perform the preoperative test
Reprints: Kathrine Holte, MD, Department of Surgical Gastroenterology, program; conversion of the operation from laparoscopic to
Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. E-mail: open procedure; history of cardiovascular, pulmonary, or
[email protected].
Copyright © 2004 by Lippincott Williams & Wilkins endocrine disease; and regular intake of any medication
ISSN: 0003-4932/04/24005-0892 except anticonceptive pills, postmenopausal estrogen supple-
DOI: 10.1097/01.sla.0000143269.96649.3b mentation, or selective serotonin reuptake inhibitors (SSRIs).

892 Annals of Surgery • Volume 240, Number 5, November 2004

Annals of Surgery • Volume 240, Number 5, November 2004 Fluid Administration in Cholecystectomy

Furthermore, patients operated in the afternoon were ex- ated list of random numbers) to intraoperative infusion of 15
cluded. During the study period, 159 patients underwent mL/kg (group 1) or 40 mL/kg (group 2) LR (composition:
elective laparoscopic cholecystectomy. Seventy-nine patients Na⫹ 130 mmol/l, K⫹ 4 mmol/l, chloride 109 mmol/l, lactate
did not meet the inclusion criteria. Of the remaining 80 28 mmol/l, calcium 1.4 mmol/l). The randomization code was
patients, 28 refused to participate in the study, 1 had surgery kept separate and not known to any of the investigators until
postponed to the afternoon, and 3 were excluded as a result of the study was completed. Double blinding was achieved by
unavailability of the investigators, leaving 48 patients for hiding the fluid infusion bags in opaque sacks ensuring
randomization. All randomized patients completed the study. blinding of the surgeons, the patients, and the investigators
The Regional Ethics Committee approved the study, and obtaining the data (B.K., K.G.N., K.H.). The fluid adminis-
subjects gave written, informed consent before inclusion. tration was controlled and administered by an anesthesiolo-
Patient demographics are shown in Table 1. Three gist (D.S.C., C.L.) not involved in patient assessments. The
patients in each group were classified as ASA II as a result of investigators obtaining patient data (B.K., K.G.N., K.H.)
a body mass index ⬎30 kg/m2. were not present during the fluid infusion. The allocated
Laparoscopic cholecystectomy was performed in a amount of LR was infused at a constant rate over 1.5 hours
semiambulatory setting (patients were encouraged but not starting immediately before induction of anesthesia. After
forced to be discharged on the day of surgery) in a public termination of the infusion, the fluid bags were discarded and
university hospital with unselected patient referral. The day the peripheral venous line closed. All patients received a
of the operation was defined as day 0. Preoperative fluid similar general anesthesia with remifentanil, propofol, and
status was standardized in all patients by ensuring that all muscle relaxants for tracheal intubation. Immediately before
fasted from midnight before the operation (all surgery per- induction of anesthesia, 8 mg dexamethasone was given to all
formed between 8 and 12 AM) and drank 175 mL of water at patients. Ventilation (O2/air: 1:2) was adjusted to keep end-
6 AM on the morning of the operation. On arrival in the tidal CO2 4.5–5.5%. At the end of surgery, 30 mg ketorolac,
operating room, patients were randomized by the sealed 4 mg ondansetron, and 0.3– 0.5 ␮g/kg sufentanil were admin-
envelope method (serially numbered, sealed, and opaque istered intravenously. Laparoscopic technique and multimo-
envelopes based on an externally generated computer-gener- dal pain management was applied as described previously.4

TABLE 1. Baseline Demographics and Surgical Data

15 mL/kg LR 40 mL/kg LR P Value

Sex (F/M) 21/3 19/5 0.70

Age (yr) 34 (21–65) 37.5 (23–63) 0.34
Preoperative weight (kg) 66.3 (48.1–96.5) 73.2 (49.0–98.1) 0.13
Height (cm) 165 (155–177.5) 168.3 (152–187) 0.15
Body mass index (kg/m2) 23.6 (19–34) 25.4 (18–37) 0.38
ASA class (I–IV) I (I–II) I (I–III) 1.00
ASA class I/II 21/3 21/3 1.00
Amount fluid infused (mL) 997.5 (721.5–1455.0) 2928 (1950–3920) ⬍0.01
Duration of surgery (min) 61.5 (28–144) 73.5 (40–215) 0.04
Duration of anesthesia (min) 94.5 (63–191) 120.5 (63–253) 0.07
Induction of anesthesia (hh:mm) 9:04 AM (8:40 AM–12:14 PM) 8:56 (8:43 AM–11:47 AM) 0.09
Blood loss (mL) 0 (0–50) 0 (0–50) 0.63
Cisatracurium (mg) 6 (4–9) 7 (5–8) 0.60
Propofol (mg) 590.9 (221.5–1222.5) 707.7 (358–1821) 0.04
Remifentanil (mg) 5.34 (3.1–10.24) 7.4 (2.8–24.0) 0.01
Propofol (mg/kg/min) 0.09 (0.02–0.13) 0.09 (0.06–0.10) 0.22
Remifentanil (␮g/kg/min) 0.87 (0.46–1.10) 0.85 (0.59–1.22) 0.79
Intraoperative sufentanil (␮g) 25 (15–35) 25 (15–40) 0.43
ETCO2 (%) 5.2 (4.1–6.0) 5.0 (4.4–5.8) 0.11
Previous motion sickness 12 11 1.00
Previous postoperative nausea and vomiting 8 8 1.00
Presently smoking 13 13 1.00

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Holte et al Annals of Surgery • Volume 240, Number 5, November 2004

In the recovery room, personnel were unaware of the assessment) should be significantly altered to conclude that
fluid regimen, and pain treatment was standardized with overall balance function was significantly altered.
sufentanil (first choice) and morphine. On-demand antiemetic
treatment was standardized and consisted of 4 mg intravenous Hormonal Responses
ondansetron once (first choice) and thereafter 0.625 mg Venous blood was drawn from a cubital vein immedi-
intravenous droperidol (second choice). Patients were al- ately before induction of anesthesia, at the end of surgery
lowed (but not forced) to drink fluids after surgery without (immediately after closing the incision), 1 and 2 hours post-
restrictions. Fluid was ingested from standard cups and the operatively. A total of 28 mL was drawn at each sampling
amount was registered 0 – 4 hours after surgery. Discharge into tubes containing appropriate additives (EDTA and apro-
from the hospital was planned to 4 hours after surgery on tinin). The concentrations of peptide hormones, antidiuretic
achieving a score of ⱖ9 according to the previously validated hormone (ADH), angiotensin II, and atrial natriuretic peptide
Postanesthesia Discharge Scoring System (PADS).5 A ward (ANP) in plasma was measured after extraction9 as previ-
nurse not involved in the study determined the PADS score ously described.10 The antibody trapping method of Poulsen
and discharged the patient. and Jørgensen11 was used to determine renin activity in
Study assessments took place preoperatively, 0, 1, 2, 4, plasma. A commercial kit (Coat-A-Count Aldosterone; Di-
and 24 hours after surgery. If discharged, patients returned to agnostic Products Corp., Los Angeles, CA) was used to
the hospital for the 24-hour assessment. measure levels of aldosterone concentrations in plasma.

Pulmonary Function Statistics

Pulmonary function (forced expiratory volume in the Data were analyzed on an intention-to-treat basis using
first second 关FEV1兴, forced vital capacity 关FVC兴, and peak nonparametric statistical methods. Data are presented as me-
expiratory flow 关PEF兴) was measured preoperatively, 1, 2, 4, dian (range). P ⬍0.05 was considered significant. Continuous
and 24 hours after surgery as described previously.6 data were compared with Mann-Whitney’s test. Categorical
data were compared using Fisher exact test. Outcome assess-
Weight
ments, including multiple measurements (balance function
The patients were weighed with standardized hospital
and visual analog scales), were analyzed with summary
clothing preoperatively 4 and 24 hours after surgery.
measures to avoid multiple comparisons. VAS were analyzed
Exercise Capacity by comparing the area under the curve (AUC) (VAS analyses
A submaximal treadmill exercise test was performed on specifically separated into early 关0 – 4 hours兴 and late
a Quinton Club Track 612 (Bothell, WA) treadmill as previ- 关evening days 0 –3兴 postoperative period). Furthermore, hor-
ously described and validated6 preoperatively, 4 and 24 hours mone concentrations at the individual time points compared
after surgery. with baseline values were compared with Wilcoxon’s test for
paired observations.
Recovery Parameters Calculation of sample size was based on the hypothesis
Self-reported registrations of pain, nausea, appetite, that administration of 15 mL/kg LR may lead to an improve-
general well-being, thirst, headache, dizziness, and drowsi- ment in pulmonary function. A previous study found a re-
ness were evaluated using a 100-mm visual analog scale duction in pulmonary function (FVC) after laparoscopic cho-
(VAS) (0 ⫽ no symptoms, 100 ⫽ worst symptoms possible) lecystectomy from 3.8 to 2.3 (40%) (standard deviation,
before surgery, 1, 2, 4, and 24 hours after surgery, and in the 0.8).12 We considered a reduction in the decrease in postop-
evening of days 0, 1, 2, and 3. Number of vomiting episodes erative pulmonary function (FVC) by 50% (from a 40% to a
were registered at the same time points (1, 2, 3, 4, or ⬎4 20% reduction) clinically relevant. With a power to detect a
episodes). Fatigue was evaluated on a 10-point fatigue scale minimal relevant difference (MIREDIF) between the 2
(1 ⫽ no fatigue and 10 ⫽ worst fatigue imaginable) before groups of 80% and a level of significance of 0.05, 21 patients
surgery and 4 and 24 hours after surgery and after discharge were needed in each group. To counter for potential patient
in the evening of days 0, 1, 2, and 3.7 exclusion after randomization, we decided to include 24
Balance Assessments patients in each group. The CONSORT guidelines13 were
Balance function was assessed with a Basic Balance followed for the report of this trial.
Master system (NeuroCom International Inc., Clackamas,
US), including 15 tests (3 static and 12 dynamic) as previ- RESULTS
ously described8 preoperatively, 4 and 24 hours after surgery. Duration of surgery was significantly longer in group 2
As a result of the multiple balance assessments obtained by (high volume), which is why significantly larger amounts of
this method, we determined a priori that a minimum of 5 of propofol and remifentanil were administered intraoperatively
the 15 tests (including at least 1 static and 1 dynamic balance in group 2 compared with group 1 (Table 1). In group 1,

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Annals of Surgery • Volume 240, Number 5, November 2004 Fluid Administration in Cholecystectomy

median 997.5 mL LR was administered intraoperatively com- 1 (P ⫽ 0.03) (Fig. 2). Twenty-four hours after surgery,
pared with 2928 mL in group 2 (Table 1). Consequently, exercise capacity did not differ between groups.
there was a significantly larger increase in weight in group 2
compared with group 1 (2.2 versus 0.8 kg 4 hours postoper- Balance Function
atively, and 1.4 versus 0.75 kg 24 hours postoperatively, P Preoperative balance function did not differ between
⬍0.01). Intraoperative hemodynamic data did not differ be- the groups. Balance function was significantly better 4 hours
tween the groups (Table 2). In the recovery room, signifi- postoperatively in group 2 compared with group 1 (6 in 15
cantly smaller amounts of sufentanil was administered in tests were significantly better—1 in 3 static tests and 5 in 12
group 2 (Table 3), as well as fewer patients (although insig- dynamic tests) (data not shown). There was no significant
nificant) required morphine, ondansetron, and sufentanil (Ta- difference in any balance function assessments between the
ble 3). Postoperative oral fluid intake was significantly larger groups 24 hours postoperatively.
in group 2 compared with group 1 (Table 4). Significantly Recovery Parameters
more patients fulfilled the discharge criteria on the day of Thirst, nausea, dizziness, and drowsiness were signifi-
surgery in group 2 compared with group 1 (23 of 24 in group cantly reduced and general well-being was significantly better
2 versus 16 of 24 in group 1, P ⬍0.02). In 3 patients (1 in in group 2 compared with group 1 in both the early (0 – 4
group 1 and 2 in group 2), overnight hospital stay was hours after surgery) and the late (from the evening on the day
mandatory because these patients were living alone (all 3 of surgery to the evening on the third postoperative day)
patients fulfilled the discharge criteria at the day of surgery). postoperative period (nausea and general well-being data:
Thus, 22 patients in group 2 and 23 patients in group 1 were early and late nausea reduced from 11 to 0 and 76 to 0,
eligible for discharge on the day of surgery, and of these respectively, in group 2 关median AUC values, P ⬍0.05
patients, significantly more (21 of 22) in group 2 were between groups兴), early and late general well-being improved
actually discharged on the day of surgery compared with from 163 to 80 and 3518 to 1962, respectively, in group 2
group 1 in which 15 of 23 patients were discharged on the day 关median AUC values, P ⬍0.05 between groups兴). Fatigue
of surgery (P ⬍0.03) (Table 4). was significantly reduced in the late but not early postoper-
Pulmonary Function ative period in group 2. No differences in either early or late
Pulmonary function did not differ between the groups pain, vomiting, appetite, or headache were seen.
preoperatively. FVC was significantly improved 2 hours
Hormonal Responses
postoperatively in group 2 compared with group 1 and FEV1
There were no significant differences between the
was significantly improved 2 and 4 hours postoperatively in
plasma concentrations of any of the measured hormones
group 2 compared with group 1 (Fig. 1). There was no
preoperatively. The significant aldosterone, ADH, and angio-
difference in peak flow (Fig. 1) at any time point between the
tensin II response to surgery in group 1 was suppressed in
groups.
group 2 (Fig. 3A), whereas the ANP response was insignif-
Exercise Capacity icantly higher in group 2 (Fig. 3B).
Exercise capacity did not differ between the groups
preoperatively. Four hours postoperatively, exercise capacity DISCUSSION
was significantly higher in group 2 with 61.5 W (range, In summary, we found that intraoperative administra-
0 –129 W) compared with 25.5 W (range, 0 –116 W) in group tion of 40 mL/kg compared with 15 mL/kg LR led to

TABLE 2. Intraoperative Hemodynamic Data

15 mL/kg LR 40 mL/kg LR P Value

Lowest systolic pressure 81 (66–94) 84 (63–113) 0.42

Highest systolic pressure 116 (94–163) 114.5 (97–156) 0.16
Systolic pressure ⬍90 (min) 12 (0–62) 12 (0–65) 0.67
Ephedrine
Patients requiring 14 12 0.78
Total dose (mg) 5 (0–35) 2.5 (0–40) 0.86
Atropine (indication: bradycardia)
Patients requiring 2 2 1.00
Total dose (mg) 0 (0–1) 0 (0–1) 1.00

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Holte et al Annals of Surgery • Volume 240, Number 5, November 2004

TABLE 3. Recovery Room Data

15 mL/kg LR 40 mL/kg LR P Value

Time spent in the recovery room (min) 102.5 (40–230) 92.5 (50–135) 0.34
Highest systolic pressure 130 (110–160) 130 (110–165) 0.93
Lowest systolic pressure 105 (85–140) 107.5 (80–130) 0.88
Ephedrine
Patients requiring 0 1 1.00
Total dose (mg) 0 (0–0) 0 (0–10) 0.32
Sufentanil
Patients requiring 14 8 0.15
Total dose (mg) 10 (0–30) 0 (0–20) 0.04
Morphine
Patients requiring 6 2 0.25
Total dose (mg) 0 (0–10) 0 (0–5) 0.10
Pethidine
Patients requiring 1 2 0.62
Total dose (mg) 0 (0–50) 0 (0–12.5) 0.59
Ondansetron
Patients requiring 5 2 0.26
Total dose (mg) 0 (0–4) 0 (0–4) 0.23
Droperidol
Patients requiring 1 0 1.00
Total dose (mg) 0 (0–1.25) 0 (0–0) 0.15

TABLE 4. Discharge Data and Data From the Ward

15 mL/kg LR 40 mL/kg LR P Value

Fluid intake 6 AM preoperatively 175 (0–175) 175 (0–175) 0.98

Oral fluid intake (0–4 hours) 537.50 (175–1175) 725 (175–1500) 0.04
Fulfilling discharge criteria (PADDS ⱖ9) on the day of surgery 16/8 23/1 0.01
Discharge on day of surgery (from potentially dischargeable patients) 15/23 21/22 0.02
Morphine consumption (4 h postoperatively)
Patients requiring 6 4 0.51
Total dose (mg) 0 (0–30) 0 (0–30) 0.42
Ondansetron (4 h postoperatively)
Patients requiring 1 0 1.00
Total dose (mg) 4 (0–4) 0 (0–0) 0.32

significant improvements in pulmonary function, exercise erative pulmonary function seen with laparoscopic surgery
capacity, balance function, subjective recovery measures compared with open surgery per se.14 Furthermore, the
(nausea, general well-being, thirst, dizziness, drowsiness, and amount of sufentanil administered in the recovery room was
fatigue) together with a significantly reduced surgical stress significantly decreased in the high-volume group and medi-
response assessed by changes in hormones influencing fluid cation for nausea (ondansetron) was also decreased, although
homeostasis, and a shortened hospital stay in patients under- not significantly in the high-volume group. These results
going laparoscopic cholecystectomy. Perioperative pulmo- were obtained despite that the group allocated to 40 mL/kg
nary function was improved by up to 50% by fluid adminis- LR had longer duration of surgery and larger amounts of
tration in this study, a clinically important improvement, administered anesthetics. We deliberately chose our fluid
which is comparable in size to the improvement in postop- regimens to reflect daily clinical practice for fluid adminis-

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Annals of Surgery • Volume 240, Number 5, November 2004 Fluid Administration in Cholecystectomy

result of concerns of adverse effects of administration of the

high volume,1 we only included healthy (ASA I/II) patients,
and only 50% of our patient population were eligible for
inclusion. Thus, our results may not be applicable to patients
with cardiovascular or other systemic diseases or patients
undergoing major surgery. Our hypothesis was that intraop-
erative fluid administration leading to perioperative fluid
excess (ie, in excess of normohydration) may adversely affect
perioperative organ functions and delay recovery, and that
restriction of intraoperative fluid administration may improve
these parameters. In this study, high-dose intraoperative fluid
administration did not alter postoperative complications as
previously suggested.1 Thus, our findings reject our hypoth-
esis. We therefore conclude that high-dose fluid administra-
tion could in fact potentially decrease complications (primar-
ily nausea and pain) and improve the perioperative course
after laparoscopic cholecystectomy; however, additional
studies are needed to further establish the optimal amount of
fluid to be administered intraoperatively in laparoscopic cho-
lecystectomy as well as other procedures.
Elective laparoscopic cholecystectomy may be consid-
ered a minor- to moderate-sized surgical procedure, with
insignificant blood and fluid losses, and the perioperative
fluid requirements to maintain normohydration may, there-
fore, approximate the preoperative fasting deficit. Presuming
a fasting deficit of 1 L, this would be covered by the 15
mL/kg LR administered in group 1 together with an oral
FIGURE 1. Effect of 40 mL/kg (high fluid) versus 15 mL/kg (low intake of 175 mL fluid on the morning of surgery and patients
fluid) lactated Ringer’s solution on pulmonary function after
being scheduled for morning procedures. The demonstrated
laparoscopic cholecystectomy. FVC, forced vital capacity;
FEV1, forced expiratory volume in 1 second. *P ⬍0.05 between
benefits of administering 40 mL/kg LR are difficult to ex-
groups. plain, but may include preoperative dehydration or surgically
induced internal shifts of fluid resulting in increased fluid
requirements.
The risk of a type I error, thus accepting a “false-
positive” result, is minimized by the observation of several
concomitant significant positive findings of high fluid admin-
istration on vasoactive hormonal reduction, perioperative
physiology, and clinical outcome (hospital stay).
Our study included measurements of various hormones
known to influence fluid and electrolyte balance (renin, aldo-
sterone, angiotensin II, ADH, and ANP). The well-known
stress response in these hormones may be mediated by an
obligatory stress-induced neurogenic reflex15 or from a phys-
iological feedback mechanism leading to a high response
FIGURE 2. Effect of 40 mL/kg (high fluid) versus 15 mL/kg (low
when functional deficits in volume or electrolytes are appar-
fluid) lactated Ringer’s solution on exercise capacity after lapa-
roscopic cholecystectomy. *P ⬍0.05 between groups.
ent or a decrease when fluid or electrolyte excess occurs. The
relative role of these mechanisms after surgical stress has not
been clarified,15 but our results of a reduced hormonal stress
tration in “minor” surgical procedures, in which fluid is often response in plasma concentrations of ADH, aldosterone, and
administered according to local guidelines and traditions and angiotensin II together with a higher ANP concentration with
not in response to specifically obtained physiological param- 40 mL/kg LR suggest that a feedback mechanism is in action.
eters. Our results may therefore have broad applicability for However, whether the altered hormonal responses represent a
daily anesthetic practice in these procedures. However, as a physiological response to a functional deficit or a response to

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Holte et al Annals of Surgery • Volume 240, Number 5, November 2004

fluid excess with 40 mL/kg LR cannot be answered, although

the beneficial effects of the high-volume regimen on organ
functions and recovery suggest that it serves to correct a
functional deficit. In this context, it is interesting that other
hormonal responses to surgery, ie, cortisol, cannot be modi-
fied by glucocorticoid administration,15 suggesting that this
response may entirely be released by a neural reflex mecha-
nism rather than be a physiological feedback mechanism.
The significantly earlier hospital discharge seen in
group 2 may have major clinical implications, because the
treatment (fluid administration) is cheap and the potential cost
reduction substantial.
Previously, numerous studies have compared different
types of fluids such as colloids, crystalloids, or hypertonic
solutions for perioperative fluid replacement.16 However, the
amounts of fluid administered have varied according to the
type of volume replacement, and conclusions on the appro-
priate amount of fluid to administer obviously cannot be
made from these studies. Several randomized studies in
high-risk patients have demonstrated that goal-directed fluid
therapy may improve outcome.17,18 However, these studies
have primarily focused on administration of fluid according
to an algorithm involving invasive monitoring (esophageal
Doppler), and the results may not be applicable to general
daily practice in minor to moderately sized surgical proce-
dures in low-risk patients. The decrease in the inflammatory
response to surgery seen with minimally invasive surgery14
may result in small perioperative fluid shifts. However, in
major abdominal surgery, with a substantially larger stress
response and altered capillary permeability, the effects of
high intraoperative fluid volumes may differ from the positive
effects on organ functions we found in the present setting.
Thus, the length of postoperative ileus has been found to
correlate with the amounts of fluid administered postopera-
tively (low fluid administration resulting in shortening of
postoperative ileus).2 Future studies should therefore address
the effects of different intraoperative fluid administration
regimens on organ functions and outcome in major surgical
procedures and in high-risk patients with comorbidity. The
present study did not support the original hypothesis that
lower fluid volumes would improve outcomes in laparoscopic
cholecystectomy. It is possible that a larger fluid administra-
tion may actually enhance clinical results.
In summary, intraoperative administration of 40 mL/kg
compared with 15 mL/kg LR for laparoscopic cholecystec-
tomy improves recovery of perioperative organ functions and
reduces hospital stay.
FIGURE 3. A and B: Effect of 40 mL/kg (high fluid) versus 15
mL/kg (low fluid) lactated Ringer’s solution on hormonal re-
sponses after laparoscopic cholecystectomy. *Significant ele-
vation (P ⬍0.05) compared with baseline values. #Significant ACKNOWLEDGMENTS
decrease (P ⬍0.05) compared with baseline values. ¤Signifi- The authors thank the anesthesia nurses and anesthesi-
cant difference (P ⬍0.05) between groups. ADH, antidiuretic ologists at the department of Anesthesiology 532, Hvidovre
hormone; ANP, atrial natriuretic peptide. University Hospital, Denmark, for helpful assistance.

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Annals of Surgery • Volume 240, Number 5, November 2004 Fluid Administration in Cholecystectomy

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