Cost-effectiveness of three combinations of antiemetics in the prevention of postoperative nausea and vomiting

F. J. Pueyo1, L. López-Olaondo*,1, M. J. Sanchez-Ledesma1, A. Ortega2 and F. Carrascosa1

1 Department of Anaesthesiology and Critical Care and 2 Department of Pharmacology, University Clinic, School of Medicine, University of Navarra, Avda. Pio XII 36, E-31007, Pamplona, Spain

Corresponding author. E-mail: llolaond@unav.es

Accepted for publication: February 25, 2003


    Abstract
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Background. This study compares the cost-effectiveness of three combinations of antiemetics in the prevention of postoperative nausea and vomiting (PONV).

Methods. We conducted a prospective, double-blind study. Ninety ASA I–II females, 18–65 yr, undergoing general anaesthesia for major gynaecological surgery, with standardized postoperative analgesia (intrathecal 0.2 mg plus i.v. PCA morphine), were randomly assigned to receive: ondansetron 4 mg plus droperidol 1.25 mg after induction and droperidol 1.25 mg 12 h later (Group 1); dexamethasone 8 mg plus droperidol 1.25 mg after induction and droperidol 1.25 mg 12 h later (Group 2); ondansetron 4 mg plus dexamethasone 8 mg after induction and placebo 12 h later (Group 3). A decision analysis tree was used to divide each group into nine mutually exclusive subgroups, depending on the incidence of PONV, need for rescue therapy, side effects and their treatment. Direct cost and probabilities were calculated for each subgroup, then a cost-effectiveness analysis was conducted from the hospital point of view.

Results. Groups 1 and 3 were more effective (80 and 70%) than Group 2 (40%, P=0.004) in preventing PONV but also more expensive. Compared with Group 2, the incremental cost per extra patient without PONV was €6.99 (95% CI, –1.26 to 36.57) for Group 1 and €13.55 (95% CI, 0.89–132.90) for Group 3.

Conclusion. Ondansetron+droperidol is cheaper and at least as effective as ondansetron+ dexamethasone, and it is more effective than dexamethasone+droperidol with a reasonable extra cost.

Br J Anaesth 2003; 91: 589–92

Keywords: antagonists, ondansetron; audit, cost effectiveness analysis; hormones, glucocorticoid, dexamethasone; hypnotics, butyrophenone, droperidol; vomiting, nausea, postoperative


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
Patients with postoperative nausea and vomiting (PONV) consume more resources and require more health care professional time than those in whom these complications are avoided. It also is associated with higher cost of care to the hospital and patient.1

Economic consequences of PONV may be important for the hospital: direct costs of emesis, longer stay in recovery room, increase discharge time, PONV-generated complications and personnel time spent in the management of emesis and complications, unplanned hospital admission and delay in resumption of normal activities. The prophylactic administration of antiemetics may reduce overall PONV-related costs.

The main end-point of this study was to compare the cost-effectiveness of the combinations: ondansetron+droperidol, dexamethasone+droperidol, or ondansetron+dexamethasone in the prevention of PONV. The relative efficacy of these combinations was reported previously.2


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
A prospective, double-blind, randomized study was conducted. Ninety women, ASA I–II, aged 18–65 yr, undergoing major elective gynaecological surgery, were studied.

The study was approved by the local ethics committee and written informed consent was obtained from all patients. Patients in Group 1 received ondansetron 4 mg and droperidol 1.25 mg after induction and 1.25 mg of droperidol 12 h later. Women in Group 2 received dexamethasone 8 mg and droperidol 1.25 mg after induction and droperidol 1.25 mg 12 h later. Those in Group 3 received ondansetron 4 mg and dexamethasone 8 mg and saline 0.9% 12 h later.

The intraoperative anaesthetic and postoperative analgesic was standardized. Complete response was defined as no nausea or EE during the 48-h postoperative period.

To perform the cost-effectiveness analysis all direct costs that could be different between groups were recorded. All drugs and supplies used in every patient and personnel time were counted. Management of emesis included the acquisition cost and materials used for administering prophylactic drugs: cost for ‘emesis clean up’, rescue antiemetic therapy and management of side effects of prophylactic and rescue therapy. Consumed resources were then transformed into costs by multiplying the number of units consumed by the cost per unit.

To make data analysis easier, a decision tree was created. Patients were divided into nine mutually exclusive subgroups, depending on the incidence of PONV, need for rescue therapy, side effects, and their treatment. The probability of being in each subgroup was obtained (Pi). Mean cost per patient for each patient subgroup was calculated (Ci). Then, the expected cost for each alternative being compared for the prevention of PONV was calculated by multiplying Ci by Pi and adding all corresponding to the same treatment group (Expected cost = {Sigma} CiPi). Finally, the incremental cost-effectiveness ratio was calculated comparing alternatives by dividing the difference in expected costs of two alternatives by the difference in efficacy of these two alternatives. Efficacy was given as the probability of being PONV-free. Therefore, the result of the incremental analysis shows how much it will cost to gain one additional PONV-free patient with one alternative compared with another.

Several one-way sensitivity analysis were then conducted to test the robustness of the results to changes in some variables such as not considering labour costs or using USA drug costs instead of Spanish drug costs. Nursing labour was estimated as the mean time dedicated to clean and take care of the patient, give antiemetic rescue and in the managing of other side effects when they occurred. This time was multiplied by the mean nurse salary to obtain the cost per episode. Then, in each branch of the decision tree, this cost was multiplied by the probability of having nausea and EE. USA drug costs were obtained from the Pharmacy Department of the University of Rochester Medical Center.

There were no significant differences among the groups in factors that could modify the incidence of PONV. A complete response occurred in 80% of the patients in Group 1, in 70% in Group 3 and in 40% in Group 2 (P<0.01).

According to the decision tree, the probability of being in each mutually exclusive subgroup was calculated for each treatment (Table 1). Direct costs were calculated for a patient in each subgroup considering labour costs and excluding these costs (Table 2).


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Table 1 Probability of being in each mutually exclusive subgroup. Group 1: ondansetron+droperidol. Group 2: dexamethasone+droperidol. Group 3: ondansetron+dexamethasone
 

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Table 2 Costs in euros per patient included in each subgroup. Group 1: ondansetron+droperidol. Group 2: dexamethasone+droperidol. Group 3: ondansetron+dexamethasone. *Excluding labour costs
 
The expected cost for a patient receiving each of the three alternative treatments was calculated. When considering labour costs, this cost (95% CI) for a patient receiving ondansetron+droperidol was 11.89 (9.41; 14.36), dexamethasone+droperidol, 9.08 (6.52; 11.66) and ondansetron+dexamethasone, 13.15 (10.64; 15.67).

Groups with ondansetron were more effective and more expensive than dexamethasone+droperidol. The incremental cost-effectiveness ratio of each of those groups vs dexamethasone+droperidol was calculated in order to estimate the extra cost of having one more PONV-free patient. This ratio was 6.99 (95% CI, –1.26; 36.57) for ondansetron+droperidol and 13.55 (0.89; 132.90) for ondansetron+dexamethasone.

Results were also analysed excluding labour cost and the findings were similar (Table 2).

When Spanish drug costs were substituted with USA costs, the results remain similar increasing the extra cost of Group 1 vs 3 per PONV-free patient to €29.5 and to €40.5 when comparing Group 3 and 2. However, these estimates decrease to figures similar to Spanish results (€13 and 23) if nursing salary is adjusted to USA values.


    Comment
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 Abstract
 Introduction
 Methods and results
 Comment
 References
 
In an era of diminished resources, the choice of one antiemetic combination is based not only on the comparative safety and effectiveness profiles but also on an economic appraisal of the consequences of a particular choice.3 Cost-effectiveness analysis can be used to determine the net cost and benefits of drugs. In our study, the combinations that include ondansetron are more effective2 and more expensive than dexamethasone+droperidol. However, the extra cost of Groups 1 and 3 per additional PONV-free patient is reasonable (€6.99 and 13.55) and we think that both of them are preferred over Group 2. When selecting between ondansetron+droperidol and ondansetron+dexamethasone, the former is cheaper and at least equally effective.

There are no clinical differences in patient outcomes and satisfaction between the use of prophylactic antiemetics and the use of antiemetics when PONV occurred, when we considered all patients, regardless of the risk of developing PONV are considered.4 However, selected high-risk surgical patients (previous history of PONV or motion sickness, female, emetogenic surgery, postoperative opioids) achieved greater satisfaction when a prophylactic antiemetic was used.5

We cannot forget that PONV is one of the most common reasons for poor patient satisfaction during the perioperative period. The recent publication of analysis of patients’ ‘willingness to pay’ suggests that the prevention of PONV is highly valued by patients. The amount patients are willing to pay for a totally effective antiemetic is US$61–113.6


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comment
 References
 
1 Watcha MF. The cost/effective management of postoperative nausea and vomiting. Anesthesiology 2000; 92: 931–3[ISI][Medline]

2 Sanchez-Ledesma MJ, López-Olaondo L, Pueyo FJ, Carrascosa F, Ortega A. A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting. Anesth Analg 2002; 95: 1590–5[Abstract/Free Full Text]

3 Watcha MF, White PF. Economics of anaesthetic practice. Anesthesiology 1997; 86: 1170–96[ISI][Medline]

4 Scuderi PE, James RL, Harris L, Mims GR,III. Antiemetic prophylaxis does not improve outcomes after outpatient surgery when compared to symptomatic treatment. Anesthesiology 1999; 90: 360–71[ISI][Medline]

5 Whatcha MF, White PF. Postoperative nausea and vomiting: prophylaxis versus treatment. Anesth Analg 1999; 89: 1337–9[Free Full Text]

6 Gan TJ, Sloan F, Dear GL, El-Moalem HE, Lubarsky DA. How much are patients willing to pay to avoid postoperative nausea and vomiting? Anesth Analg 2001; 92: 393–400[Abstract/Free Full Text]