1 All India Institute of Medical Sciences, New Delhi, India. 2 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 3 Northern General Hospital, Sheffield Teaching Hospital NHS Trust, Sheffield, UK. *Corresponding author: Department of Anesthesia, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Harvard Medical School, Boston, MA 02115, USA
This work was supported by institutional and departmental sources. The study was presented at the annual meeting of American Society of Anesthesiologists.
Accepted for publication: March 6, 2002
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Abstract |
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Methods. One hundred and fifty children were randomly assigned to either prophylactic (P) or early symptomatic treatment only (T) group (n=75). Children in group P received ondansetron 100 µg kg1 i.v. and those in group T received placebo at the end of the procedure. After surgery, at the earliest sign of nausea or vomiting, children in both groups received ondansetron 100 µg kg1 i.v. Besides the incidence of PONV, non-surrogate (fast tracking time, duration of stay in the postanaesthesia care unit (PACU) and parental satisfaction scores), therapeutic (numbers needed to prevent and treat) and pharmacoeconomic (cost to benefit a child and cost per PONV-free child) outcome measures were evaluated.
Results. The incidences of PONV in the immediate, early, late and first 24-h periods were significantly less in group P (20, 12, 19 and 35% respectively) than in group T (37, 29, 47 and 72%, P<0.05). Time to achieve fast-track eligibility and duration of PACU stay were significantly shorter in group P (P<0.001). Children in group P had superior mean (SD) parental satisfaction scores (8.2 (1.8)) compared with those in group T (6.8 (1.7), P<0.001). The number needed to prevent PONV was 2 and the number needed to treat PONV was 9. The cost to benefit a child was more than fourfold less and the cost per PONV-free child was 35% less in group P.
Conclusions. Compared with early symptomatic treatment with ondansetron, prophylactic ondansetron shortened fast-tracking time and duration of PACU stay and improved parental satisfaction and therapeutic outcomes at a lower direct cost.
Br J Anaesth 2002; 89: 4738
Keywords: vomiting, postoperative nausea and vomiting; vomiting, antiemetics, ondansetron; anaesthesia, audit
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Introduction |
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This trial evaluated the effectiveness of prophylactic ondansetron versus early treatment of PONV with ondansetron in children undergoing strabismus repair, a population with a high risk of PONV. Fast track eligibility time, duration of stay in the postanaesthesia care unit (PACU), parental satisfaction and therapeutic and pharmacoeconomic outcome measures were also compared.
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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 vecuronium 100 µg kg1 i.v., and anaesthesia was maintained with halothane and 66% nitrous oxide along with meperidine 0.5 mg kg1 i.v. A random number generator was used to assign each child prospectively to either the prophylactic (P) or the therapeutic (T) group (n=75). At the end of the procedure (when the last extraocular muscle was repaired), children in group P received ondansetron 100 µg kg1 i.v. (maximum of 4 mg) and children in group T received saline. The study drugs were prepared by an anaesthetist not directly 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 neostigmine 50 µg kg1 and glycopyrrolate 10 µg kg1 and the trachea was extubated when the child was awake.
All children were transported to the PACU, where they stayed for a minimum of 2 h for initial evaluation and management and for assessment of eligibility for fast tracking. One of the study personnel assessed postanaesthetic recovery, using a modified Aldretes scoring system,5 and the time to achieve eligibility for fast tracking [6] (fast tracking time, FTT). Time to achieve complete recovery (a modified Aldrete recovery score of 10) was recorded for all children. FTT was calculated as the time from the discontinuation of anaesthesia to the time at which a child had patent airway without support, no PONV and pain, and a modified Aldrete recovery score of 10. The criteria for discharge from the PACU to the 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/or pain were observed in the PACU until they had been free of PONV and pain for 1 h.
All episodes of PONV in the first 24 h in the hospital were recorded at intervals of 02, 26 and 624 h 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 younger children (less than 6 yr of age). In older children, nausea was assessed by an observer asking the child whether he or she had any nausea, in addition to self-reporting. Any child having an episode of vomiting or nausea was treated with ondansetron 100 µg kg1 i.v. (maximum 4 mg) as the first postoperative antiemetic. If ondansetron failed to control nausea and vomiting in 30 min, metoclopramide 150 µg kg1 and promethazine 0.5 mg kg1 were used as the rescue antiemetics (second and third choices respectively).
Postoperatively, analgesia was provided when older children complained or younger children cried in pain.7 Oral ibuprofen 10 mg kg1 was administered as the analgesic of first choice and, for pain in children who had PONV, ketorolac 0.5 mg kg1 i.v. was administered as the analgesic of second choice. Intravenous fluid consisted of lactated Ringers solution to replace the fluid deficit plus maintenance fluids in the recovery room.
Finally, at the end of 24 h after surgery, the health-care worker who stayed with the child for most of the time was asked to give a global assessment of satisfaction over the entire postoperative experience of the child on the basis of the presence or absence of nausea, vomiting, pain and other adverse events. Parental satisfaction scores were obtained using an 11-point verbal linear numerical scoring system (0=not at all satisfied, 10=fully satisfied).
Power analysis before the study showed that 68 children would be required in each group to give an 80% chance (ß=0.2) of detecting a 25% absolute reduction in the incidence of PONV between the groups for a basal PONV incidence of 55% with a type-1 error of 5% (Epi Info, version 6.04b; Center for Disease Control, Atlanta, GA, USA and World Health Organization, Geneva, Switzerland, 1997).
Two sample t-tests and the MannWhitney U-test were used to compare the age, weight, durations of anaesthesia, recovery and PACU stay, FTT, perioperative fluid and analgesic requirements and parental satisfaction. The incidences of PONV and rescue antiemetic requirements were compared by the 2 and Fishers exact tests with Yates continuity correction wherever appropriate. The positive numbers needed to prevent and treat (NNP and NNT) PONV were calculated as the reciprocals of absolute risk reductions of incidences of PONV from our institutes basal incidence of 83%1 for children who received ondansetron prophylactically and early symptomatic treatment respectively. Similarly, the number needed to improve satisfaction (NNS) was calculated as the reciprocal of the absolute percentage of unsatisfied parents (parental satisfaction score <7.5).
The cost to benefit a child was calculated as the drug (ondansetron) acquisition cost per child multiplied by NNT (treatment) or NNP (prevention). The ondansetron acquisition cost per child was calculated by multiplying its acquisition cost in our institution by the mean weight (kg) of the children in each group. For the pharmacoeconomic analysis, we assumed the institutional acquisition costs of 1 mg of ondansetron, 10 mg of metoclopramide and 25 mg of promethazine as US$4, US$0.29 and US$1.25 respectively. The direct antiemetic cost per PONV-free child was calculated by dividing the total acquisition costs of all antiemetics administered (including ondansetron administered prophylactically in group P) by the number of PONV-free children in each group.
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Results |
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Children in the prophylactic ondansetron group had significantly higher parental satisfaction scores than those in the therapeutic group (8.2 (1.8) vs 6.8 (1.7), P<0.001) (Table 3). More parents of children in the prophylactic ondansetron group had greater satisfaction (score of 7.5 or more) than parents of children in the therapeutic ondansetron group (64 vs 25.3%, P<0.0001). The positive number needed to improve satisfaction (NNS) was 3.95 in the early treatment group and 1.56 in the prophylactic group.
The cost to benefit a child with ondansetron was US$17.8 in the prophylactic group and US$76.7 in the early therapeutic group. The total direct cost of all antiemetics per PONV-free child was 35.5% less with prophylactic ondansetron (US$21.3) than with early treatment (US$28.9).
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Discussion |
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Strabismus repair is associated with the highest risk of PONV in children.1 8 Routine prophylactic use of ondansetron has been demonstrated recently to improve true outcome measures after strabismus repair in children, as well as reducing the incidence of PONV.1 However, prophylaxis with ondansetron in a heterogeneous (varying PONV risk) adult population undergoing ambulatory surgery has been shown not to improve outcomes after outpatient surgery compared with early symptomatic treatment.4 Our study, in a homogeneous population of children with a high risk of PONV, demonstrated that prophylactic ondansetron was more effective than the early treatment.
Most studies on PONV reported only surrogate measures, such as the incidence of PONV and the number of emetic episodes per patient. Use of surrogate outcomes alone in PONV studies has been criticized.2 In our trial, we used parental satisfaction scores for the childs perioperative experience, the duration of PACU stay and FTT as the true outcome measures. In addition, we evaluated the number needed to treat and prevent PONV.3 The NNT was 9 but the NNP was 2, indicating that alternate children benefited from prophylactic ondansetron.
Fast tracking after general anaesthesia, which has cost-reducing potential, involves transferring patients directly from the operating room to a less labour-intensive step-down unit. The time to reaching eligibility for fast tracking was shorter in the prophylactic group compared with the treatment group (Table 3). The shorter FTT in the prophylactic group can be attributed to the significant reduction in the incidence of PONV in the immediate postoperative period and the decreased need for rescue antiemetics. Transfer of patients directly from the operating room to a less labour-intensive recovery area may decrease costs.9 10 The children in our study stayed in the hospital for 24 h for social and health-care access reasons and we utilized this extended stay to assess the safety of fast tracking and to assess late PONV. Early and safe fast tracking achieved with prophylactic ondansetron reveals its cost-saving potential in this high-risk population. The FTT could have been even shorter in our study had we used propofol and sevoflurane, which were not available to us at the time of this study. As it is unusual to keep children in hospital for 24 h after strabismus surgery in other parts of the world, in order to make our findings relevant to others we measured FTT and the duration of PACU stay when we analysed costbenefit.
PONV after ambulatory surgery is one of the leading causes of delay in discharge from the PACU, unanticipated hospital admission and increase in medical costs.1113 The duration of PACU stay was shorter in children who received prophylactic ondansetron and it could have been even shorter, especially in the prophylactic group, had we used criteria based on discharge alone and not fixed the minimum duration of PACU stay at 2 h (which we needed for initial evaluation of outcomes and management). We did not assess another clinically and economically important outcome, the rate of unanticipated hospital admission, as all our patients were inpatients for 24 h. Even if the children had been discharged immediately after surgery, it would have been difficult to compare the incidence of this infrequent event because of our relatively small sample size.11 12
In this era of value-conscious health care, the cost of a drug or practice to benefit a patient is a significant factor. Value-based care is essentially the best patient outcome achieved at a reasonable cost.14 15 This is the first clinical trial that has evaluated the utility of prophylactic vs prompt therapeutic use of ondansetron on the basis of value-based care principles.14 15 Children in the prophylactic ondansetron group had significantly higher parental satisfaction scores than those in the therapeutic group. The lower cost to benefit a child and lower cost per PONV-free child in the prophylactic ondansetron group reassert the value of prophylaxis with ondansetron as a cost-effective modality compared with early symptomatic treatment in high-risk patients. Even though prophylactic ondansetron was a cost-effective approach, the higher cost of ondansetron has been a major concern. Recently, it has been demonstrated that prophylactic dexamethasone administered at induction is cost-effective in managing PONV after paediatric strabismus repair.16 However, as a sole prophylactic antiemetic, neither dexamethasone nor ondansetron was adequate to eliminate PONV completely in this high-risk population.16 Scuderi and colleagues have recently shown that multimodal management of PONV decreases the incidence of PONV better than prophylactic ondansetron alone in a population with a high risk of PONV.17
For an individual patient, the use of routine prophylactic ondansetron compared with wait and treat may increase the direct drug costs. However, we believe that the downstream benefits (higher patient satisfaction, earlier fast tracking and shorter PACU stay) more than compensated for the additional cost.
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