| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
| ||||||||||||||
| ||||||||||||||
|
|
|
|
||||||||||||
|
||||||||||||||
*Department of Anaesthesia and Intensive Care Medicine, University College Hospital; and Department of Anaesthesia, Clinical Sciences Institute, National University of Ireland, Galway, Ireland
Address correspondence to Dr. J. G. Laffey, Department of Anesthesia, Clinical Sciences Institute, National University of Ireland, Galway, Ireland. Address e-mail to john.laffey{at}nuigalway.ie.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Intravascular volume deficits may be a factor in PONV and perioperative administration of IV fluids may reduce the incidence of adverse outcomes in outpatient surgery (8,9). Perioperative administration of a sufficient volume of IV fluids to correct this deficit may effectively prevent PONV, without the expense or potential for side effects seen with pharmacologic approaches to this problem. However, studies of perioperative fluid administration have used differing methodologies and have drawn conflicting conclusions (8,10–13). Therefore, the potential efficacy of IV fluid therapy in reducing PONV remains to be convincingly demonstrated.
One key factor may be that many of these studies contained patients at low baseline risk for PONV. McCaul et al. (12), in a study of patients undergoing diagnostic gynecologic laparoscopy, found an incidence of PONV of 22% within the first 24 postoperative hours. Until recently, it has been difficult to predict which patients will develop PONV. However, a validated predictive scoring system for PONV now offers the potential to selectively identify and target those patients likely to develop PONV (6). This scoring system identifies four primary risk factors for PONV in patients receiving balanced anesthesia: female gender, nonsmoking status, history of motion sickness or PONV, and the use of postoperative opioids (6). In addition, the type of ambulatory surgical procedure may also increase PONV risk, with up to 88% of patients undergoing ambulatory gynecologic laparoscopy reporting PONV (1).
We wished, therefore, to examine the hypothesis that the administration of large volume IV fluids to patients at high risk for PONV undergoing ambulatory gynecologic laparoscopy would reduce the incidence and/or severity of this important and distressing phenomenon.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients were randomized to two groups by sealed envelopes and both the patient and their anesthesiologist were blinded to their group assignment. The fluid volume to be administered was calculated on the basis of the interval since last oral intake (called hereafter the "fasting time"). The control group (control) received a perioperative fluid bolus of 3.0 mL/kg compound sodium lactate (CSL), whereas the large volume infusion group (large volume) received a perioperative CSL volume of 2.0 mL · kg–1 · h–1 of fasting time. This volume was administered in both groups before induction of anesthesia over approximately 20 min by an anesthesiologist not otherwise involved in the clinical care of the patient.
All patients received a standardized general anesthetic. Standard monitoring, including electrocardiogram, noninvasive arterial blood pressure, arterial oxygen saturation, end-tidal carbon dioxide, and volatile anesthetic were used throughout. Before induction of anesthesia, all patients were given IV fentanyl (1–1.5 µg/kg). A sleep dose of propofol (2–3 mg/kg) was titrated to induce anesthesia, with atracurium 0.35 mg/kg used to facilitate tracheal intubation. In all patients, the lungs were mechanically ventilated for the duration of the procedure and anesthesia was maintained with sevoflurane (1%–3%) in a mixture of nitrous and oxygen in a 2:1 ratio. Pharmacologic antiemetic prophylaxis was not given. No further fluids were administered during the operative period. In the event that patients developed intraoperative hypotension, or excessive blood loss occurred, the patient was withdrawn from the study, data collection was discontinued, and further fluid management was at the discretion of the primary anesthesiologist. At the end of the surgical procedure, all patients received infiltration of their abdominal incisions with 10 mL of 0.25% bupivacaine. Muscle relaxation was then antagonized with neostigmine (2.5 mg) and glycopyrrolate (0.5 mg), diclofenac 100 mg was administered rectally, anesthesia was discontinued, and the endotracheal tube removed upon resumption of spontaneous ventilation. The patient was then moved to the postanesthesia care unit (PACU).
An investigator blinded to the patient group assessed the patients postoperatively. Patients were assessed by interview using a standardized questionnaire at five time intervals. First, in PACU when conversant; second, 1 h later on discharge from the PACU; third, 4 h later in the ward area; and at 24 and 72 h postoperatively, by telephone.
Nausea was measured using a verbal analog scale (VAS, 0 = no nausea, 10 = worst imaginable) scoring system. A PONV episode was defined as the occurrence of nausea (score 1–10), vomiting, or need for antiemetic therapy. The severity of nausea was further classified based on the highest VAS PONV score as mild (VAS 1–2), moderate (VAS 3–5), or severe (VAS 6–10). Rescue antiemetics were offered to any patient who complained of nausea or vomited before hospital discharge. This consisted of ondansetron 4 mg IV, which could be repeated once, followed by IM prochlorperazine 12.5 mg if necessary. At postdischarge follow-up, patients were also asked whether or not they vomited and whether they required antiemetic therapy after discharge. Pain was also recorded using a 0–10 VAS scoring system. On-demand analgesia was given to patients complaining of pain (morphine 2 mg IV p.r.n. in PACU; codeine 30 mg and/or acetaminophen 1 g per os 8 hourly p.r.n. after discharge).
We based our sample size estimation on the incidence of PONV. For the purposes of sample size calculation, we considered that a clinically important reduction in the incidence of PONV in these high risk patients would be a 30% absolute reduction in PONV. We projected an incidence of PONV of 80% in the untreated group, based on our previous observations, previous reported incidence in this type of surgery (14), and predictive risk scoring (6). Based on these figures, using an 
= 0.05 and ß = 0.2, for an experimental design incorporating 2 equal sized groups, we estimated that 40 patients would be required per group.
Statistics were performed using a standard statistical program (SPSS© version 11.0; SPSS Inc., Chicago, IL). Demographic data were analyzed using Student's t-test or Fisher's exact test as appropriate. Repeated measurements (nausea VAS scores, pain VAS scores) were analyzed by repeated measures analysis of variance, with further paired comparisons at each time interval performed using the t-test, with corrections for multiple comparisons where appropriate. Categorical data were analyzed using 
2 analysis or Fisher's exact test where applicable. Normally distributed data were presented as means ± sem, non-normally distributed data were presented as medians ± quartiles (interquartile range), and categorical data were presented as raw data and as frequencies. The level for all analyses was set as P < 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
The overall incidence of PONV in the first 72 postoperative hours (control 87% versus large volume 59%) was significantly (P < 0.05) reduced in the large volume group compared with control (Fig. 1). The frequency of nausea was significantly (P < 0.05) reduced in the large volume group compared with control at 4, 24, and 72 h postoperatively (Fig. 1). The frequency of both moderate and severe nausea was significantly reduced in the large volume group (Table 2). The number needed to treat (NNT) to prevent an occurrence of PONV was 3.45 (95% confidence interval, 2.63–5.0). Mean postoperative VAS nausea scores were significantly (P < 0.05) lower in the large volume group compared with the control group in the PACU and at 1, 4, 24, and 72 h postoperatively (Fig. 2). Mean worst postoperative nausea scores were significantly (P < 0.05) lower in the large volume group compared with the control group at both the 4–24 and 25–72 h postoperative time intervals (Table 2). Postoperative antiemetic requirements, in terms of the number of patients requiring antiemetic therapy, and the mean ondansetron dose, were significantly (P < 0.05) reduced in the large volume group compared with control (Table 2, Fig. 3).
|
|
|
|
Mean postoperative VAS pain scores were significantly (P < 0.05) lower in the large volume group compared with the control group in the PACU and at 1, 24, and 72 h postoperatively (Fig. 4). Mean worst postoperative pain scores were significantly (P < 0.05) lower in the large volume group compared with the control group at both the 4–24 and 25–72 h postoperative time intervals (Table 3). Postoperative supplemental analgesic requirements, in terms of the number of patients requiring morphine, the mean morphine requirement, the number of patients requiring oral analgesics, and the mean acetaminophen requirement were significantly (P < 0.05) reduced in the large volume group compared with control (Table 3, Fig. 3). In addition, there was a clear trend to reduced postoperative requirement for codeine in the large volume group, although this was not statistically significant (Table 3).
|
|
The finding that large volume IV fluids decreased postoperative pain and opioid requirements raised the possibility that this could alone account for the decreased PONV, with the IV fluids having little direct effect. Postoperative opioid therapy is a known risk factor for PONV (6). However, between group differences in postoperative opioid requirement did not account for the reduced incidence of PONV in the large volume group. The risk of PONV based on Apfel et al.'s (6) criteria was calculated using the three preoperative criteria only (sex, smoking status, and history of motion sickness or PONV) and then calculated using all four Apfel criteria (Table 1). This isolated the contribution of the requirement for postoperative opioids to the risk of PONV in our patients. There was no significant contribution of postoperative morphine requirement to the risk of PONV in either group (Table 1). In addition, in the control group, the incidence of PONV in patients who required morphine was 92% compared with 80% in control patients who did not require morphine.
Finally, postoperative opioid requirement did not contribute to the need for antiemetic prophylaxis in the control group. Of the 24 patients in the control group who required postoperative morphine, 12 required antiemetic therapy whereas 12 did not require antiemetic therapy.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Large volume preoperative IV rehydration has been proposed as a method of reducing PONV (8–14). However, studies of preoperative IV rehydration have drawn conflicting conclusions (8–14). McCaul et al. (12) were unable to demonstrate a decrease in PONV after the administration of CSL 1.5 mL · kg–1 · h–1 of fasting, with and without added dextrose 0.5 g/kg, in patients undergoing diagnostic gynecologic laparoscopy. Cook et al. (9) also found no decrease in PONV in patients undergoing gynecologic laparoscopy given 20 mL/kg CSL. Conversely, Ali et al. (14) demonstrated that preoperative administration of 15 mL/kg CSL decreased the incidence of PONV in patients undergoing a combination of laparoscopic gynecologic or abdominal procedures or open abdominal surgery. Yogendran et al. (8), in an important study, demonstrated that 20 mL/kg of an isotonic electrolyte solution decreased the incidence of several adverse symptoms, in a diverse population of male and female ambulatory surgical patients undergoing gynecologic, orthopedic, and general surgical procedures. However, this study failed to convincingly demonstrate the potential for preoperative large volume IV fluid therapy to attenuate PONV (8). Although they did report a trend to a reduced incidence of nausea at all time points in their study, this difference was not significantly different, with the exception of the final time point studied, i.e., at 24 hours (8).
These reported differences in the potential for preoperative IV fluids to reduce PONV may have resulted from the methodologic limitations in these studies. Specifically, important sources of potential bias existed, such as a failure to eliminate important potential confounders, including gender (8,11), type of surgery (8,11), differences in anesthetic technique (8), and differences in the amounts of intraoperative fluid administration (14). In addition, the criteria for the diagnosis of PONV in several studies were relatively insensitive (8–11,13,14), and the postoperative follow-up times were generally limited (8–14). Furthermore, these studies focused on patients at relatively low baseline risk for PONV, and may not have been sufficiently large to detect a treatment effect in this patient group (8–14).
The potential for preoperative large volume IV fluid therapy to reduce PONV in ambulatory surgical patients remains unclear. In fact, recent consensus guidelines regarding the management of PONV do not recommend large volume preoperative IV fluid therapy to reduce the risk of PONV (7). A clear determination of whether IV fluid administration decreases PONV is required for two reasons. First, large volume IV fluid administration, admittedly using volumes well in excess of that used in this study, has been demonstrated to transiently decrease pulmonary function in volunteers (16). Thus, aggressive fluid administration may not be entirely devoid of side effects. Second, the administration of large volumes of IV fluid imposes logistic and practical difficulties in a busy ambulatory facility, and there are associated cost implications.
Our aim in this study was to definitively test the hypothesis that preoperative large volume IV fluid therapy attenuates PONV. Our study focused on the specific subgroup of patients at most risk for PONV, and eliminated potential confounders such as the effects of gender, or of type of surgery or anesthesia. We therefore confined recruitment to patients undergoing ambulatory gynecologic laparoscopy that were at high risk for PONV, using the Apfel score, a validated risk scoring system (6). Furthermore, given that the purpose of preoperative IV fluid therapy is to correct accumulated fluid deficits, we elected to take duration of fasting into account when calculating fluid requirements in the large volume group. We extended our data collection up to 72 hours postoperatively, given that the only significant reduction in nausea in the study by Yogendran et al. (8) occurred at the final time point studied, i.e., at 24 hours postoperatively. This raised the possibility that the effect of large volume fluids on PONV might be delayed beyond 24 hours postoperatively. Furthermore, because of the relatively insensitive method of detecting nausea used in previous studies, we decided to actively elicit a VAS score for nausea for all patients at each time point.
Our study clearly demonstrates, for the first time, the potential for large volume IV fluid therapy to markedly attenuate the incidence of PONV in high risk patients. This is the patient group for which effective therapies to attenuate PONV are most urgently required, as evidenced by the frequent incidence of PONV in these patients in our study. The frequent detected incidence of PONV was contributed to by the sensitivity of the detection tool (i.e., verbal rating scales, in which a score more than zero at any time point was taken to indicate the presence of nausea), and the relatively long postoperative follow-up period. If the analysis is limited to the incidence of moderate to severe nausea, then the incidence of nausea seen in the control group, at 54%, is almost exactly that predicted by Apfel's criteria. Of importance, the large volume IV fluid therapy was most effective in reducing the incidence of moderate and severe nausea in these high risk patients. Large volume IV fluids markedly reduced both the mean severity of nausea and the worst nausea scores in these patients, and the need for antiemetic therapy, at all time points studied. A further novel finding is the fact that the treatment effect was prolonged, and was still present at 72 hours postoperatively. The clinical significance of the treatment effect, as determined by an NNT analysis (17), suggests one needs to treat 3.45 patients with large volume fluid administration to prevent 1 episode of PONV. This figure compares favorably with that for ondansetron 4–8 mg, for which the NNT to prevent nausea is 6–7 (7).
Our study is the first to clearly demonstrate the potential for large volume IV fluids to markedly reduce postoperative pain. Large volume IV fluids markedly reduced both the mean severity of pain and the worst pain scores in these patients, and the need for supplemental parenteral opioid and oral analgesia, at all time points studied. There were no surgical reasons for the between group differences in postoperative pain profiles. A further novel finding is that the treatment effect was prolonged, and was still present at 72 hours postoperatively. However, this important and novel finding is not without precedent. In fact, a close examination of other studies of preoperative fluid regimens does reveal evidence for reduced postoperative pain with large volume preoperative IV fluid therapy, although this has received little attention. Ali et al. (14) demonstrated a marked trend toward less opioid and nonsteroidal antiinflammatory use in the patients who received the larger volume IV fluids. In fact, Ali et al. reported that patients in the large volume group required 50% less fentanyl in the first postoperative hour, and 50% less morphine and 50% less ketorolac in the first 24 postoperative hours, although these differences were not statistically significant (14). In the study by Yogendran et al. (8), less patients in the large volume group required postoperative morphine. Cook et al. (9) reported less codeine and acetaminophen use in the large volume group of their study. In fact, large volume IV fluids significantly reduced the combined need for analgesic and antiemetic medication in their study (9). Ooi et al. (10) reported that few patients who received preoperative IV fluids complained of moderate or severe postoperative pain. Conversely, McCaul et al. (12) found that large volume rehydration with a solution containing dextrose resulted in an increased requirement for opiate therapy in the PACU, compared with an equal volume of Ringer's lactate solution or no IV fluids. This increase in postoperative fentanyl requirement was likely caused by the presence of dextrose in the IV fluid, given that this did not occur with Ringer's lactate solution alone. In summary, the potential for preoperative IV fluid regimens to modulate the severity of postoperative pain and analgesic requirements is clear. Our study provides the first clear demonstration of the analgesic potential of preoperative large volume IV fluids. The mechanism underlying these analgesic effects remains to be determined.
The finding that large volume IV fluids decreased postoperative pain and opioid requirements raised the possibility that this could alone account for the decreased PONV, with the IV fluids having little direct effect. Postoperative opioid therapy is a known risk factor for PONV, as recognized by Apfel et al.'s criteria (6). However, our analysis of the contribution of postoperative opioid therapy to the risk of PONV indicates that between group differences in postoperative opioid requirement do not account for the increased incidence of PONV in the control group. In fact, although postoperative morphine requirement did increase the risk for PONV in both groups, and this effect was more pronounced in the control group, it did not significantly contribute to the risk of PONV. In addition, the requirement for morphine had only a minor effect on the incidence of PONV within the control group, with similar levels of PONV seen in control patients who did not receive postoperative morphine. Finally, postoperative opioid requirements did not contribute to the need for antiemetic prophylaxis in the control group. Thus, preoperative large volume IV fluid administration decreased PONV by a mechanism largely independent of its potential to reduce opioid requirements. A likely mechanism by which large volume preoperative IV rehydration reduces PONV is the correction of intravascular volume deficits, thereby minimizing the potential for splanchnic ischemia, a potential cause of PONV (14).
There are several limitations that deserve careful examination when considering the clinical significance of this study. First, caution must be exercised in generalizing from these data to different patient populations. The clinical efficacy of IV fluid administration in preventing PONV is likely to be substantially less in patients with a lower baseline risk for PONV. Nevertheless, the fact that IV fluid administration effectively attenuates the incidence and severity of PONV in high risk patients provides strong support for its use in all ambulatory surgical patients. Second, our patients received individualized, preoperative fluid therapy, calculated to replace the deficit incurred by mandatory fasting. This imposes logistic difficulties in a busy ambulatory surgical unit and may be impractical in all clinical settings. However, it seems logical to account for duration of fasting in correcting perioperative fluid deficits, and this is supported by our findings. Third, our patients had relatively long fasting times, of the order of 12–13 hours. This occurred despite clear preoperative fasting instructions to fast for 6–8 hours from solids, depending on the type of food consumed, and to refrain for 4 hours from fluids. These guidelines are similar to that currently advocated by the ASA, and are similar to those in other similar recently published clinical studies (12,14). Nevertheless, our findings might therefore be less relevant to patient groups in which substantially shorter fasting times are permitted and achieved. Finally, although this was a population with a high predicted baseline risk of PONV, antiemetic prophylaxis was not used. However, the use of universal PONV prophylaxis remains controversial (18) and prophylaxis with ondansetron prevents nausea only in one-fifth of those patients to whom it is administered (18). In our study, patient distress was minimized by the provision of immediate, IV antiemetic therapy to all patients complaining of nausea before hospital discharge. This minimized the severity of nausea and the incidence of vomiting in our patients, and is reflected in the relatively low mean VAS nausea scores at all time intervals in our study.
In conclusion, we report for the first time the potential for large volume preoperative IV administration of a balanced salt solution to significantly reduce the incidence and severity of PONV, and pain in patients at high risk for PONV. The potential for large volume IV fluids to produce a sustained reduction in PONV is novel, and seems to be independent of its ability to reduce postoperative pain and opioid and simple analgesic requirements. We recommend the administration of a volume of 2 mL/kg for every hour of fasting to high risk patients undergoing ambulatory surgical procedures.
The authors sincerely thank Dr. Conan McCaul for his advice and help regarding the design of the study, and the Medical and Nursing staff of the Department of Obstetrics and Gynaecology, University College Hospital, for their assistance in conducting the study.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  E. Deflandre, V. Bonhomme, and P. Hans Delta down compared with delta pulse pressure as an indicator of volaemia during intracranial surgery Br. J. Anaesth., February 1, 2008; 100(2): 245 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Holte, B. B. Kristensen, L. Valentiner, N. B. Foss, H. Husted, and H. Kehlet Liberal Versus Restrictive Fluid Management in Knee Arthroplasty: A Randomized, Double-Blind Study Anesth. Analg., August 1, 2007; 105(2): 465 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. White, H. Kehlet, J. M. Neal, T. Schricker, D. B. Carr, F. Carli, and the Fast-Track Surgery Study Group The Role of the Anesthesiologist in Fast-Track Surgery: From Multimodal Analgesia to Perioperative Medical Care Anesth. Analg., June 1, 2007; 104(6): 1380 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Baumgarten The Real Ultrasound Revolution Anesth. Analg., May 1, 2007; 104(5): 1292 - 1292. [Full Text] [PDF]
|
|
|
|
|
|
K. Tominaga and T. Nakahara The Twenty-Degree Reverse-Trendelenburg Position Decreases the Incidence and Severity of Postoperative Nausea and Vomiting After Thyroid Surgery Anesth. Analg., November 1, 2006; 103(5): 1260 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Way, R. Dhamrait, A. Wade, and I. Walker Perioperative fluid therapy in children: a survey of current prescribing practice Br. J. Anaesth., September 1, 2006; 97(3): 371 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Gan Risk factors for postoperative nausea and vomiting. Anesth. Analg., June 1, 2006; 102(6): 1884 - 1898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. White, J. Tang, M. A. Hamza, B. Ogunnaike, M. Lo, R. H. Wender, R. Naruse, A. Sloninsky, R. Kariger, S. Cunneen, et al. The use of oral granisetron versus intravenous ondansetron for antiemetic prophylaxis in patients undergoing laparoscopic surgery: the effect on emetic symptoms and quality of recovery. Anesth. Analg., May 1, 2006; 102(5): 1387 - 1393. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
