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© 2000 International Anesthesia Research Society
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Abstract |
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This study compares intrathecal (IT) fentanyl with IV ondansetron for preventing intraoperative nausea and vomiting during cesarean deliveries performed with spinal anesthesia. Thirty healthy parturients presenting for elective cesarean delivery with standardized bupivacaine spinal anesthesia were randomized to receive 20 µg IT fentanyl (Group F) or 4 mg IV ondansetron (Group O) by using double-blinded methodology. At eight specific intervals during the surgery, a blinded observer questioned the patient about nausea (1 = nausea, 0 = no nausea), observed for the presence of retching or vomiting (1 = vomiting or retching, 0 = no vomiting or retching), and recorded a verbal pain score (0–10, 0 = no pain, 10 = worst pain imaginable). Cumulative nausea, vomiting, and pain scores were calculated as the sum of the eight measurements. Intraoperative nausea was decreased in the IT fentanyl group compared with the IV ondansetron group: the median (interquartile range) difference in nausea scores was 1 (1, 2), P = 0.03. The incidence of vomiting and treatment for vomiting was not different (P = 0.7). The IT fentanyl group had a lower cumulative perioperative pain score than the IV ondansetron group; the median difference in the cumulative pain score was 12 (8, 16) (P = 0.0007). The IT fentanyl group required less supplementary intraoperative analgesia. The median difference in the cumulative fentanyl dose was 100 (75, 100) µg fentanyl, (P = 0.0002).
Implications: Intrathecal fentanyl as part of a spinal anesthetic for cesarean delivery is superior to IV ondansetron for the prevention of intraoperative nausea. In addition, intrathecal fentanyl offers better perioperative pain control and is less expensive than ondansetron.
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Introduction |
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Intraoperative nausea and vomiting occurs in as many as 66% of cesarean deliveries performed under regional anesthesia (1). This can be distressing to the patient, can make the surgery difficult to perform, and may increase the risk of aspiration of gastric contents (1).
Several antiemetics are proven to diminish this problem. IV metoclopramide and droperidol reduce the incidence of intraoperative nausea during cesarean delivery (1,2). Unfortunately, there are significant side effects with these medications. Droperidol may cause extrapyramidal symptoms and dysphoria (3). Metoclopramide is rarely associated with dystonic reactions (3) and may exacerbate stress-induced tachycardia (4). The 5-HT3 antagonists (ondansetron, granisetron) are also effective in reducing nausea in this setting (5,6). Although these medications have a low incidence of side effects, high acquisition costs may discourage routine use.
Intrathecal lipophilic opioids (fentanyl, sufentanil) increase both the duration and intensity of spinal anesthesia (7–11) and decrease intraoperative nausea and vomiting (8–11). IT fentanyl is inexpensive and has few serious side effects, making it an attractive drug for intraoperative nausea and vomiting prophylaxis. Although both IV ondansetron and IT fentanyl have demonstrated efficacy in preventing nausea and vomiting during cesarean delivery, no direct comparative studies have been performed. Therefore, we designed a randomized, double-blinded clinical study comparing IT fentanyl with IV ondansetron for the prevention of intraoperative nausea and vomiting during elective cesarean delivery under spinal anesthesia.
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Methods |
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After institutional review board approval and written informed consent, 30 ASA physical status I or II parturients presenting for elective cesarean delivery were enrolled. Parturients with a history of motion sickness, hyperemesis gravidarum, contraindications to regional anesthesia, or allergies to the study medications were excluded. Subjects were randomized in blocks of 10 to one of two groups by using computer-assisted allocation. A person uninvolved in the study had previously prepared sealed envelopes containing each subject’s group assignment. Study drugs were prepared by an anesthesiologist not involved in this study and dispensed in unlabeled syringes.
The IT fentanyl group received 20 µg (0.4 mL) IT fentanyl, and 2 mL IV normal saline immediately after the placement of the spinal. The IV ondansetron group received 0.4 mL IT normal saline and 4 mg (2 mL) IV ondansetron after spinal placement. All subjects received 12 mg hyperbaric bupivacaine for spinal anesthetic. Thirty milliliters per os sodium bicitrate and an IV bolus of 500 mL of lactated Ringer’s solution were administered to each subject before arrival in the operating room. No other premedication was given.
Spinal anesthesia was performed by using a 25-gauge Whitacre needle at the L2–3 or L3–4 interspace. Immediately after the intrathecal injection, subjects were placed supine with left uterine displacement while a 1000-mL lactated Ringer’s fluid bolus was given. The level of sensory blockade was recorded 10 min after IT injection. Standard monitors were used, and noninvasive blood pressure measurements were performed at 2-min intervals for 10 min, then 5-min intervals for the remainder of the procedure. All patients received supplemental oxygen via nasal cannula throughout the procedure. Hypotension was treated with IV ephedrine (5–15 mg) and additional 250-mL boluses of IV fluid. Patients who complained of pain were given 50-µg increments of IV fentanyl. Vomiting or retching by patients in either study group was treated with 4 mg of IV ondansetron. Pruritus was treated with 25 mg IV diphenhydramine. At the end of the procedure, all patients received 30 mg IV ketorolac, which was repeated every 6 h for 24 h postoperatively. Each patient also received morphine by patient-controlled analgesia (PCA), which was available in the recovery room and was continued for at least 24 h. PCA parameters were 1-mg bolus, 10-min "lockout" interval, with no continuous infusion.
Study variables were assessed by an observer blinded to treatment group assignment at eight sequential intervals during the procedure: spinal placement until skin incision, skin incision until delivery, delivery until uterine exteriorization, uterine exteriorization until replacement of uterus, uterine replacement until start of fascial closure, fascial closure until skin closure, skin closure until arrival in recovery room, and recovery room stay (approximately 1 h). At each interval, an observer questioned the patient about the presence or absence of nausea, observed for the presence of retching or vomiting, and requested a verbal pain score (0–10, 0 = no pain, 10 = worst pain imaginable.) A total of eight measurements were recorded for each patient. To reduce the degrees of freedom, nausea (1 = nausea, 0 = no nausea), vomiting vomiting (1 = retching or vomiting, 0 = no retching or vomiting), and pain scores were summed across the eight measurements. Other variables recorded included perioperative fentanyl usage, intraoperative ephedrine usage, the interval between spinal placement and first request for postoperative analgesics, and PCA morphine usage during the first 6 and 24 h postoperatively. Differences between the groups were evaluated by using the Wilcoxon-Mann-Whitney U-test as appropriate. Median values with confidence intervals were estimated by using the Hodges-Lehmann algorithm using exact estimation; exact 75% confidence intervals were used as the IQR (interquartile range). Data were reported as mean ± SD or as median (IQR). A Spearman’s correlation test was performed to evaluate an association between perioperative nausea and perioperative fentanyl use and between perioperative nausea and perioperative pain. Fisher’s exact test was used for binary variables. Statistical software was StatXact-4 for Windows (CYTEL Software Corporation, Cambridge, MA).
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Results |
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There were 15 patients in each of the two study groups. Maternal characteristics were not different between the two groups (Table 1). An adequate surgical block was documented in all patients (>T4) before the start of the operation. Summary values for responses variables are listed in Table 2.
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Perioperative nausea occurred less frequently with IT fentanyl compared with IV ondansetron; the median difference in number of episodes of nausea was 1 (1,2) (P = 0.03).
Perioperative vomiting or retching was similar for IT fentanyl and IV ondansetron; the median difference in number of episodes of vomiting or retching was 0 (0, 0) (P = 0.65).
The IT fentanyl group had a lower cumulative perioperative pain score than the IV ondansetron group; the median difference in the cumulative pain score was 12 (8,16) (P = 0.0007). The IT fentanyl group required less supplementary intraoperative analgesia. The median difference in the cumulative fentanyl dose was 100 (75, 100) µg fentanyl (P = 0.0002). Ten patients in the IV ondansetron group and no patient in the IT fentanyl group required supplemental perioperative analgesia. To account for the possibility of intraoperative nausea being correlated with perioperative treatment with IV fentanyl (cumulative amount) or with the cumulative sum of the perioperative pain scores, a Spearman’s correlation test was performed. There was no association between nausea and fentanyl (r = -0.16, P = 0.57) or between nausea and pain score (r = 0.09, P = 0.64).
The IT fentanyl group needed less ephedrine for the treatment of intraoperative hypotension than the IV ondansetron group; the median difference in the total dose was 10 (0, 20) mg ephedrine, (P = 0.03). A Spearman’s correlation test found no significant correlation between ephedrine requirements and nausea (r = 0.40, P = 0.19). No patients required treatment for pruritus, and all patients maintained adequate oxygenation (SaO2 
97%) with nasal cannula supplemental oxygen.
Postoperatively, the IT fentanyl group had decreased morphine requirements in the first 6 h postintrathecal injection compared with the IV ondansetron; the median difference in the 6-h total dose was 5.5 (1, 10) mg morphine (P = 0.01). No difference was found in the time interval between the spinal and the first request for analgesia. No statistically significant difference was found in the morphine usage from 6 to 24 h postspinal or in the total 24-h morphine usage (Table 2). Apgar scores at 1 min and 5 min were not different between the groups (Table 2).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Nausea and vomiting commonly occurs during cesarean delivery performed with regional anesthesia (1) and is frequently related to peritoneal traction and exteriorization of the uterus. These problems may be accompanied by visceral pain, which occurs despite apparently adequate dermatomal sensory blockade (12). Various prophylactic antiemetics have been used. Metoclopramide, droperidol, and the 5-HT3 antagonists (ondansetron, granisetron) are all effective in decreasing intraoperative nausea and vomiting during cesarean delivery. Unfortunately, side effects and cost issues may limit routine use. Pan and Moore (5) compared prophylactic droperidol and ondansetron during cesarean delivery and recommended consideration of ondansetron on the basis of equivalent efficacy and decreased side effects. However, ondansetron, may cause transient headaches and mild elevation of liver enzymes (13). More significantly, 5-HT3 drugs are expensive. At the University of Utah, the acquisition cost for 4 mg of ondansetron is $8.14 vs $0.21 for an 2-mL ampule of fentanyl.
IT lipophilic opioids have been studied extensively as adjuvants to spinal anesthesia for cesarean delivery (14) and may provide improved intra- and postoperative analgesia (7–11). An additional benefit is decreased intraoperative nausea and vomiting. Dahlgren et al. (8) studied women undergoing cesarean delivery and added either 10 µg fentanyl, 2.5 µg sufentanil, 5 µg sufentanil, or saline placebo to IT bupivacaine. All of the groups receiving IT lipophilic opioids had significantly less intraoperative vomiting. Palmer et al. (9) reported decreased nausea and vomiting in patients who received 15 µg fentanyl added to lidocaine spinal anesthesia. Randalls et al. (10) studied the effects of adding epinephrine and fentanyl, individually or in combination, to bupivacaine spinal anesthesia. Epinephrine increased and IT fentanyl decreased the incidence of intraoperative nausea. Finally, Cooper et al. (11) also observed decreased intraoperative nausea when 25 µg of fentanyl was added to bupivacaine spinal anesthesia for cesarean delivery. We chose 20 µg for our IT fentanyl dose because it was midrange for doses quoted in the literature (9,11).
Because both IT fentanyl and IV ondansetron decrease nausea and vomiting during cesarean delivery, we felt it unnecessary (and perhaps unethical) to include a placebo control group. Our results showed that patients receiving IT fentanyl had significantly less intraoperative nausea compared with the patients receiving IV ondansetron. By using median values, the patients receiving IT fentanyl had 1.5 episodes of intraoperative nausea compared with 2.5 in the IV ondansetron group.
Because the increased incidence of intraoperative nausea in the IV ondansetron group could have been related to the increased need for intraoperative IV fentanyl, a Spearman’s correlation test was performed to examine the relationship between the two variables. No correlation between the two was observed. Thus, it is unlikely that the increased incidence of intraoperative nausea of patients in the IV ondansetron group was caused by the increased use for intraoperative IV fentanyl. This conclusion is consistent with earlier studies on parenteral morphine, in which nausea was rarely evident in the supine, nonmoving patient. Emetic episodes associated with parenteral opioids typically occur in conjunction with patient movement, suggesting a vestibular component to the mechanism of opioid-induced emesis (3).
Hypotension occurs commonly with spinal anesthesia and was aggressively treated in our study with IV fluid and boluses of IV ephedrine. We observed a significant decrease in ephedrine requirements for the IT fentanyl group compared with the IV ondansetron group. The cause of this is unclear, but may involve a greater need for IV fentanyl supplementation during surgery in the ondansetron group. Although a Spearman’s correlation test was not significant, small sample size may not permit adequate study of this issue. Subjects in both groups received the same dose of IT bupivacaine, no patient in our study had a level of spinal blockade >T2, and no patient in either group had hypotension that did not respond rapidly to treatment.
Pruritus is another common side effect of IT opioids and at times may be quite distressing to the patient. Various studies have reported that pruritus seems to occur more commonly at larger IT opioid doses (8,15). Although pruritus was not studied, no patient requested or received treatment.
There have been reports of life-threatening respiratory depression when IT lipophilic opioids have been used for labor analgesia (15,16). During cesarean delivery, however, significant sedation or respiratory depression has not been seen (7–11). Intense monitoring, verbal stimulation, and routine supplemental oxygen may minimize the clinical significance of any mild respiratory depression that might occur. In our study, no patient in either group experienced clinically significant sedation or had oxygen saturations lower than 97%.
Although Apgar scores were similar between the two groups (Table 2), we acknowledge that this is not a highly sensitive means of neonatal assessment. Umbilical cord blood gas analysis and neonatal neurobehavioral scores may have revealed more subtle effects.
Postoperative morphine requirements were decreased in the IT fentanyl group for the first six hours postspinal, although no difference was seen in the time interval from the spinal to the first request for postoperative analgesia. However, it should be noted that 10 patients in the ondansetron group had already received supplemental IV fentanyl during surgery. There was a trend toward increased morphine requirements in the IT fentanyl group from 6 to 24 hours after spinal placement, although this did not reach statistical significance (P = 0.06). The 24-hour morphine usage was not different between the groups. Our findings have some similarities to a previous study by Cooper et al. (11), in which patients who received IT fentanyl had greater postoperative morphine requirements from 6 to 23 hours after spinal placement. They suggested that the most likely explanation for this finding was an acute spinal opioid tolerance induced by the IT fentanyl. The small size of our study, combined with the use of parenteral ketorolac as part of our postoperative analgesic regimen, may have obscured this relationship.
Finally, our study excluded parturients with a history of motion sickness and hyperemesis gravidarum. However, patients undergoing cesarean delivery under spinal anesthesia are inherently at high risk for intraoperative nausea and vomiting. Although IT fentanyl appears superior to IV ondansetron as a single drug to prevent perioperative nausea, it is possible that treatment with multiple drugs with different sites of action might benefit certain patient groups.
The limitations of this study include small sample size, which may prevent detection of subtle differences between groups. Also combination therapy was not investigated. As an example, would combined IV ondansetron and IT fentanyl be superior to IT fentanyl alone? In addition, no dose-response curve was performed for either IT fentanyl or IV ondansetron. Although both drug doses are commonly used in contemporary clinical practice, it is possible that a larger dose of ondansetron would have been more effective or a lower dose of fentanyl would have been sufficient.
In summary, our study suggests that 20 µg IT fentanyl is superior to 4 mg IV ondansetron for the prevention of perioperative nausea during cesarean delivery performed with bupivacaine spinal anesthesia. IT fentanyl is cost effective, has a low incidence of serious side effects, and greatly improves the quality of surgical anesthesia, making it an attractive drug in this setting for routine use.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Lussos SA, Bader AM, Thornhill ML, Datta S. The antiemetic efficacy and safety of prophylactic metoclopramide for elective cesarean delivery during spinal anesthesia. Reg Anesth 1992;17:126–30.[Web of Science][Medline]
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Santos A, Datta S. Prophylactic use of droperidol for control of nausea and vomiting during spinal anesthesia for cesarean section. Anesth Analg 1984;63:85–7.
[Free Full Text] - Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment and prevention. Anesthesiology 1992;77:162–84.[Web of Science][Medline]
- Eisenach JC, Dewan DM. Metoclopramide exaggerates stress-induced tachycardia in pregnant sheep. Anesth Analg 1996;82:607–11.[Abstract]
- Pan PH, Moore CH. Intraoperative antiemetic efficacy of prophylactic ondansetron versus droperidol for cesarean section patients under epidural anesthesia. Analg 1996;83:982–6.[Abstract]
- Fujii Y, Tanaka H, Toyooka H. Granisetron prevents nausea and vomiting during spinal anaesthesia for caesarean section. Acta Anaesthesiol Scand 1998;42:312–5.[Web of Science][Medline]
- Hunt CO, Naulty JS, Bader AM, et al. Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989;71:535–40.[Web of Science][Medline]
- Dahlgren G, Hultstrand C, Jakobsson J, et al. Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section. Anesth Analg 1997;85:1288–93.[Abstract]
- Palmer CM, Voulgaropoulos D, Alves D. Subarachnoid fentanyl augments lidocaine spinal anesthesia for cesarean delivery. Reg Anesth 1995;20:389–94.[Web of Science][Medline]
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Randalls B, Broadway JW, Browne DA, Morgan BM. Comparison of four subarachnoid solutions in a needle-through-needle technique for elective caesarean section. Br J Anaesth 1991;66:314–8.
[Abstract/Free Full Text] -
Cooper DW, Lindsay SL, Ryall DM, et al. Does intrathecal fentanyl produce acute cross-tolerance to i.v. morphine? Br J Anaesth 1997;78:311–3.
[Abstract/Free Full Text] - Alahuhta S, Kangas-Saarela T, Hollmen AI, Edstrom HH. Visceral pain during caesarean section under spinal and epidural anaesthesia with bupivacaine. Acta Anaesthesiol Scand 1990;34:95–8.[Web of Science][Medline]
- Castle WM, Jukes AJ, Griffiths CJ, et al. Safety of ondansetron. Eur J Anaesthesiol 1992;9 (Suppl 6):63–6.
- Hamber EA, Viscomi CM. Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth 1999;24:255–63.
- Lu JK, Schafer PG, Gardner TL, et al. The dose-response pharmacology of intrathecal sufentanil in female volunteers. Anesth Analg 1997;85:372–9.[Abstract]
- Hays RL, Palmer CM. Respiratory depression after intrathecal sufentanil during labor. Anesthesiology 1994;81:511–2.[Web of Science][Medline]
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