Department of Anaesthesiology and Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110 029, India. 1Beth Israel Deaconess Medical Centre, Boston, MA02215, USA. 2All India Institute of Medical Sciences, New Delhi, India. 3Bedford General Hospital, Bedfordshire, UK*Corresponding author
Accepted for publication: July 19, 2000
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Abstract |
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Br J Anaesth 2001; 86: 849
Keywords: vomiting, nausea; vomiting, antiemetics
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Introduction |
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Materials and methods |
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Children were not premedicated. Anaesthesia was induced with halothane and nitrous oxide in oxygen via a facemask or with i.v. thiopental. After induction of anaesthesia and establishment of venous access, tracheal intubation was facilitated with 100 µg kg1 i.v. vecuronium, and anaesthesia was maintained with halothane and nitrous oxide along with 0.5 mg kg1 of i.v. meperidine. A random number generator was used to assign each child prospectively to receive dexamethasone 1 mg kg1 (maximum 25 mg), ondansetron 100 µg kg1 (maximum 4 mg) or saline placebo. The study drugs were prepared by an anaesthetist not otherwise involved in patient care, to a fixed volume of 5 ml, to maintain the double-blind nature of the study. Intraoperative i.v. fluid management consisted of administration of lactated Ringers solution sufficient to correct half of the preoperative fluid deficit in the first hour, followed by maintenance fluids according to body weight. At the end of the procedure, residual neuromuscular blockade was antagonized with 50 µg kg1 of neostigmine and 10 µg kg1 of glycopyrrolate and the trachea was extubated when the child was awake. The gastric contents were aspirated by suction via a tube passed before extubation. No nasogastric tube was left in situ during the procedure.
After operation, all children were transported to the postanaesthesia care unit (PACU). The anaesthetist who provided intraoperative care assessed postanaesthetic recovery using the modified Aldrete scoring system.4 Time to achieve complete recovery (score 10) was recorded for all children. After operation, analgesia was provided when older children complained or younger children cried in pain.5 Oral ibuprofen 10 mg kg1 was given as the analgesic of first choice, and for pain in children who had PONV in the immediate postoperative period in the PACU, ketorolac 0.5 mg kg1 i.v. was administered as the analgesic of second choice by the anaesthetist who provided intraoperative care. Intravenous fluid comprised lactated Ringers solution replacing the remaining fluid deficit plus maintenance fluids in the recovery room.
All episodes of nausea and vomiting in the first 24 postoperative hours in the hospital during the intervals of 06 h and 624 h were evaluated using a numeric scoring system for PONV (0=no nausea or vomiting, 1=nausea but no vomiting, 2=vomiting once in 30 min or more, 3= persistent nausea (>30 min) or two or more vomits in 30 min) by the PACU and ward nursing staff, who were aware of the nature of the study but blinded to the study drug. We did not assess nausea in very young children (less than 6 yr of age). In older children, nausea was assessed by an observer and by self-reporting. Any child having a PONV score of 3 was considered to have severe PONV and was treated with metoclopramide 150 µg kg1 i.v. as a rescue antiemetic. The time to achieve eligibility for fast tracking (fast tracking time, FTT) was calculated as the time from the discontinuation of anaesthesia to the time at which the child had a patent airway without support, no PONV, no pain and a recovery score of 10.
The criteria for discharge from PACU to ward included stable vital signs, adequate pain control and no nausea and vomiting in the first 2 h after surgery. Children who had PONV and pain in the first 2 h of stay were observed in PACU till they had remained free of PONV and pain for an hour.
Finally, at the end of 24 h after surgery, the primary caretaker was asked to give a global assessment of their satisfaction over the entire postoperative experience of the child (parental satisfaction score) using an 11-point verbal numeric scoring system (0=not at all satisfied, 10=fully satisfied).
Statistical analysis
Power analysis before the study showed that 41 children would be required in each group to have a 95% chance (ß=0.05) of detecting a 50% relative reduction in PONV, from our Institutes basal incidence of 80%6 with a type-1 error of 5% (=0.05) and 95% confidence interval limits (Version 6.04b, Epi Info, Centre for Disease Control, Atlanta, GA, USA, and World Health Organization, Geneva, Switzerland, 1997). Two-sample t-tests and Mann Whitney U-tests were used to compare the age, weight, duration of surgery, anaesthesia, recovery, fast tracking and PACU stay, perioperative fluid and analgesic requirements, and the parental assessment scores of the childs perioperative experience. The incidence and severity (requirement of rescue antiemetic) of PONV were compared by
2 and Fishers exact tests with Yates continuity correction wherever appropriate. The positive number needed to prevent (NNTP) PONV (which indicates how many children had to be exposed to dexamethasone or ondansetron to prevent PONV) was calculated as the reciprocal of the absolute risk reduction of the incidences of PONV from the basal (placebo) incidence for children who received dexamethasone or ondansetron. The cost to benefit a child was calculated as the drug acquisition cost per patient times the NNTP for dexamethasone or ondansetron. P-values less than 0.05 were considered statistically significant, and data are presented as mean (SD) unless otherwise specified.
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Results |
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Recovery time was comparable in all groups. The FTT was similar in the ondansetron (28.4 (31.7) min) and dexamethasone (36.6 (44.5) min) groups (P=0.67). The FTT in the placebo group (67.5 (60.00) min) was significantly greater than that in the ondansetron (P=0.0003) and dexamethasone (P=0.007) groups. Duration of stay in the PACU was significantly longer in the placebo group (153.66 (41.41) min) than in the ondansetron (P=0.0002) and dexamethasone (P=0.007) groups, but comparable between the ondansetron and dexamethasone groups (P=0.16). The positive NNTP was comparable in the ondansetron (NNTP=2.36) and dexamethasone (NNTP=1.95) groups. The number of postoperative analgesic supplements in dexamethasone group (1.04 (0.7)) was significantly lower than in the ondansetron (1.7 (0.5)) and placebo (1.7 (0.7)) groups (P=0.0000) but comparable in the ondansetron and placebo groups (P>0.99). In the dexamethasone group, 11.1 and 7.1% of the children had facial flushing and headache respectively, and 8.8% of children in the ondansetron group had headache (Table 3). The parental assessment scores for the childrens perioperative experiences were comparable in the dexamethasone and ondansetron groups (P=0.08). Children in the ondansetron and dexamethasone groups had significantly higher parental satisfaction scores than those in placebo group (P<0.0001).
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Discussion |
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Dexamethasone has been shown to be an effective antiemetic in children undergoing ambulatory adenotonsillectomy.3 13 Though the mechanisms of its antiemetic effects are still unclear, it may act through prostaglandin antagonism,14 serotonin inhibition in the gut15 and by releasing endorphins.16
In our study, the incidence of PONV was 33.3% in the ondansetron group, 24.4% in the dexamethasone group and 75.6% in the placebo group. Dexamethasone was as effective as ondansetron in decreasing the incidence and severity of PONV in the first 24 h after operation. The antiemetic efficacy of dexamethasone was most pronounced in the late postoperative period. The incidence and severity of PONV in the late postoperative period were significantly lower in the dexamethasone group than in the ondansetron and placebo groups. This prolonged antiemetic efficacy of dexamethasone may be explained by its prolonged biological half-life (3672 h). Similar findings have been reported in patients undergoing ambulatory surgery.13 17 18 Dexamethasone has been shown to provide greater protection from delayed chemotherapy-induced nausea and vomiting compared with ondansetron19 and granisetron.20
In this trial, the groups were comparable with respect to patient characteristics, surgical procedure, anaesthetics administered and i.v. fluids used in the perioperative period. Therefore, the difference in the incidence and severity of PONV and true and therapeutic outcome measures among the groups in this trial can be attributed to the study antiemetics that were administered.
Betamethasone prophylaxis has been shown to decrease postoperative pain and late PONV in ambulatory surgical patients.21 In our study, the requirement for postoperative analgesic supplements was significantly lower in the dexamethasone group. The antiemetic and analgesic effects of dexamethasone were more pronounced in the late postoperative period. This probably added to the comfort of the patients when they were discharged home.
In our trial, we used parental assessment scores of the childs perioperative experience, duration of PACU stay and fast tracking time as true outcome measures. Dexa methasone was as effective as ondansetron in improving true outcome measures in this group of patients.
We included a placebo group to allow us to calculate the absolute reduction in the risk of PONV, and thereby the NNTP. The NNTP indicates how many children need to be exposed to the treatment in order to prevent PONV in one of them. Meta-analyses have reported that the best NNTP with the well-documented regimens were between 4 and 6 for ondansetron1 and 4 for dexamethasone.22 In our trial, NNTP with dexamethasone (1 mg kg1) and ondansetron (100 µg kg1) was approximately 2. In the meta-analyses,1 22 NNTP was reported to be greater possibly because of the heterogeneous patient population and defects in the meta-analyses of PONV.6 23
The timing of prophylactic antiemetic administration is important. We administered the drugs at the beginning of the procedure. It has been confirmed recently that dexamethasone is more effective when administered at induction than when given at the end of anesthesia.24 Though it has been suggested that ondansetron given at the end of surgery will reduce antiemetic requirements more effectively in the postoperative period,25 in short surgical procedures like strabismus surgery administering ondansetron at the beginning or end of surgery did not affect the outcome.26
In this pharmacoeconomic era, the cost to benefit a patient for prophylactic antiemetic is a significant factor. In the ondansetron group, the acquisition cost of drug per patient was 18.6 times higher than in the dexamethasone group. The cost to benefit a patient (i.e. NNTP times the cost of drug per patient) was 22 times higher in the ondansetron group than in the dexamethasone group. This reasserts the value of prophylactic dexamethasone as a cost-effective alternative to ondansetron.
Facial flushing was seen in five children (11%) after administration of dexamethasone. There were no associated haemodynamic changes in any of these patients. We requested the surgeons to inform us if any child was admitted with wound infection or delayed wound healing. There were no wound-related problems in any group. Headache was seen in three, four and two children in the dexamethasone, ondansetron and placebo groups respectively. Our sample size was inadequate to identify an adverse effect with an incidence of less than 2.2% (100/45). Meta-analysis may be effective in identifying adverse effects with low incidence. The recent meta-analysis on dexamethasone and PONV did not reveal any significant side-effects.22 As yet, there is no evidence in the literature for dexamethasones potential side-effects, such as hyperglycaemia, delayed wound healing and hypothalamicpituitary adrenal axis suppression after a single dose.
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