|Year : 2019 | Volume
| Issue : 3 | Page : 161-165
Cost-effectiveness and efficacy of combined dexamethasone–metoclopramide versus ondansetron in the prevention of postoperative nausea and vomiting in women undergoing myomectomy under spinal anesthesia
TA Ogbo1, IT Ekwere1, Kingsley Ufuoma Tobi2, NP Edomwonyi1
1 Department of Anaesthesiology, University of Benin Teaching Hospital, Benin City, Nigeria
2 Department of Surgery and Anaesthesiology, University of Namibia, Windhoek, Namibia
|Date of Submission||25-Nov-2019|
|Date of Acceptance||25-Nov-2019|
|Date of Web Publication||23-Jan-2020|
Dr. Kingsley Ufuoma Tobi
Department of Surgery and Anaesthesiology, University of Namibia, Windhoek
Source of Support: None, Conflict of Interest: None
Background: Postoperative nausea and vomiting (PONV) is a common complication following surgery under spinal anesthesia. The aim of this study was to compare the efficacy and cost-effectiveness of metoclopramide–dexamethasone combination with ondansetron as prophylaxis against PONV in the routine gynecological surgeries amenable to subarachnoid block (SAB). Materials and Methods: Following institutional ethical approval, patients were randomly assigned to receive either ondansetron 4 mg or metoclopramide 10 mg plus dexamethasone 8 mg. All patients had a SAB with 3 ml of 0.5% hyperbaric bupivacaine plus 25 μg of fentanyl. The primary outcome was proportion of patients in both groups with PONV within 24 h from institution of the SAB. Secondary outcome included comparison of severity of PONV between the two study groups, incidence of side effects related to the study drugs (i.e., sedation, headaches, and movement disorder), and cost implication of the study drugs in both groups. Results: One hundred patients were recruited in this study. The overall incidence of PONV for the 24-h period was 10% (n = 5) and 12% (n = 6) for the ondansetron group and the combination group, respectively. Side effects of the study drugs were minimal and comparable in both groups. The cost-effectiveness ratio, evaluated based on the number of women completely free of nausea and vomiting in each group, was higher at ₦ 177.78 for group ondansetron compared to ₦ 113.63 for metoclopramide and dexamethasone combination group. Conclusion: Combined dexamethasone–metoclopramide had comparable clinical effectiveness with lower cost-effectiveness compared to ondansetron for the prevention of PONV in women undergoing myomectomy under SAB.
Keywords: Antiemetic, myomectomy, postoperative nausea and vomiting, subarachnoid block
|How to cite this article:|
Ogbo T A, Ekwere I T, Tobi KU, Edomwonyi N P. Cost-effectiveness and efficacy of combined dexamethasone–metoclopramide versus ondansetron in the prevention of postoperative nausea and vomiting in women undergoing myomectomy under spinal anesthesia. Bali J Anaesthesiol 2019;3:161-5
|How to cite this URL:|
Ogbo T A, Ekwere I T, Tobi KU, Edomwonyi N P. Cost-effectiveness and efficacy of combined dexamethasone–metoclopramide versus ondansetron in the prevention of postoperative nausea and vomiting in women undergoing myomectomy under spinal anesthesia. Bali J Anaesthesiol [serial online] 2019 [cited 2020 Feb 28];3:161-5. Available from: http://www.bjoaonline.com/text.asp?2019/3/3/161/276628
| Introduction|| |
Postoperative nausea and vomiting (PONV) continues to be a major problem among surgical patients., Besides its negative impact on patient's satisfaction, PONV may also delay discharge, cause unanticipated hospital readmission, cause wound dehiscence, cause bleeding from surgical sites, increase postoperative pain, cause aspiration of gastric contents, and electrolyte imbalance.,
The incidence of PONV varies for surgeries under general and spinal anesthesia, 25%–40% and 33.33%, respectively. The occurrence of nausea and vomiting during gynecological surgeries done with subarachnoid blocks (SAB) can be attributed to various reasons. First, the female sex is a well-established independent predictor of PONV., Furthermore, the occurrence of hypotension (decrease in blood pressure (BP) of more than 20%–30% below baseline value) and dermatomal block higher than the fifth thoracic segment can predispose to PONV. Furthermore, gynecological surgery on its own has been recognized as a potential risk factor for increased incidence of PONV as traction on the peritoneum and exteriorization of the uterus during some surgeries may trigger nausea and vomiting. Another factor that may predispose patients to PONV during SAB may include the use of intrathecal opioids.,
Management and prevention of PONV is a critical aspect of the care of the surgical patient. However, the purpose of antiemetics for the treatment of PONV has been observed to be unprofitable compared to their prophylactic usage., Most widely published guidelines recommend serotonin receptor (5-HT3) blocker as one of the first-line PONV prophylactic agent , with ondansetron being the most commonly used. It was described as the “gold standard” in comparison to other antiemetics and is more effective in treating vomiting than nausea.
Ondansetron has been shown to reduce the incidence of PONV by as much as 50% in patients with high risk for PONV. However, it is expensive and not readily available in our environment. Furthermore, the current guidelines on the management of PONV emphasize a multimodal approach which is targeted at identifying patients at risk of PONV, reducing their baseline risk, and using interventions targeted at different steps of the vomiting pathway. Furthermore, a combination of antiemetic agents acts synergistically while requiring lower doses of each drug.
In our environment, metoclopramide is the most widely used antiemetic because it is relatively inexpensive, readily available, and safe. It was reported that metoclopramide is a safe and effective drug for PONV prophylaxis, especially in low-resource countries. However, the benefits of an intravenous (IV) dose of 10mg when compared to placebo have been debated by an earlier study. Dexamethasone has also been shown to be a cost-effective, safe, and effective medication for prevention of nausea and vomiting. In addition, metoclopramide–dexamethasone combination for PONV prophylaxis has been demonstrated by local studies to be particularly useful for gynecological surgeries.,
The study thus hoped to compare the efficacy and cost-effectiveness of metoclopramide–dexamethasone combination with ondansetron as prophylaxis against PONV in the routine gynecological surgeries amenable to SAB.
| Materials and Methods|| |
This was a prospective, randomized, double-blind study. The study was carried out in the University of Benin Teaching Hospital (UBTH), a tertiary health care facility situated in Benin City, Edo state Nigeria.
The study population was drawn from female patients scheduled for elective myomectomy under SAB. These included patients in American Society of Anesthesiologists (ASA) classification I or II and female patients aged 21–46 years scheduled for myomectomy under SAB. Exclusion criteria are patient's refusal, patients with known hypersensitivity to study drugs, patients with previous history of motion sickness, patients on antiemetic or steroid therapy, patients with gastrointestinal, liver, or renal diseases and patients with a history of extrapyramidal motor disease, psychiatric illness, seizure disorder, smokers, and patients with contraindications for spinal anesthesia.
Ethical clearance was obtained from the Research and Ethics Committee of the UBTH. A data and safety monitoring board supervised this study and assessed adverse complications resulting from the use of the study drugs. During preoperative evaluation, eligible patients were identified and the study including risk and benefits was explained to them. Written informed consent was obtained from those who accepted to participate in the study.
Randomization of patients was done by a resident doctor blinded to the study protocol on the day of surgery by balloting. “Group A” (ondansetron) or “Group B” (metoclopramide plus dexamethasone) was written on 100 pieces of paper (50 for each group) and then sealed in small opaque envelopes. All sealed envelopes were placed in a large-sized bag. The bag was thoroughly shaken each time a patient was about to pick a ballot paper, and based on which paper was picked, the patient was randomized into either Group A or B. The already picked ballot paper was thereafter returned into the opaque envelop, stapled on the study sheet, and was only reopened at the conclusion of the study.
For Group A, 4 mg (2 ml) of ondansetron and 2 ml of normal saline (all in separate 2 ml syringes) were prepared, while for Group B patients, 8 mg (2 ml) of dexamethasone and 10 mg (2 ml) of metoclopramide were drawn up by the theater pharmacist. The investigator who was blinded to patient allocation as well as study drugs administered the drugs, observed the patients for the study outcomes and collated the study data. Study participants were also blinded to which study drugs were given to them.
On arrival of the patient in theater, a multiparameter monitor (manufactured by GE Medical System Information Technology International, Wisconsin USA) was attached and baseline vital signs, namely pulse rate (PR), BP, mean arterial pressure (MAP), arterial oxygen saturation (SpO2), and electrocardiogram (ECG) were obtained and were recorded.
IV access was secured with a size 18G or 16G cannula for each patient, and preloading of the circulation was done with 15 ml/kg of warm 0.9% saline. Before instituting the SAB, Group A patients received intravenously 4 mg (2 ml) of ondansetron with 2 ml of normal saline (from two separate 2 ml syringes) while Group B patients were given intravenously 8 mg of dexamethasone and 10 mg (2 ml) of metoclopramide (also from two separate 2 ml syringes).
SAB was established with the patient in the sitting position under strict aseptic technique with 0.1% chlorhexidine and methylated spirit following which the back was covered with a sterile-fenestrated draping. The L3/L4 or L4/L5 interspace was identified using the iliac crest as a landmark and the skin infiltrated with 2 ml of 2% plain lidocaine. A 25G Quincke spinal needle was passed through a 20G short needle as an introducer at this level using a midline approach, and the spinal needle was advanced gently into the subarachnoid space. The subarachnoid space was identified when clear free-flowing cerebrospinal fluid was seen at the hub of the spinal needle after removal of the stylet. Each patient received 3 ml of 0.5% hyperbaric bupivacaine plus 25 μg of fentanyl.
On withdrawal of the needle, dry sterile dressing was applied over the injection site and secured with plaster. The patient was thereafter repositioned supine with the head and shoulder supported with a pillow to prevent excessive rostral spread of the anesthetic drug. The level of sensory block was assessed by loss of sensation to cold using cotton wool soaked in methylated spirit and surgery commenced on attaining a block height of T4–T6 after two consecutive assessments. If SAB height was not adequate for surgery, general anesthesia was performed and such patients were excluded from the study.
Following establishment of spinal anesthesia, BP was measured and recorded every minute for the first five minutes and thereafter every five minutes till the end of surgery. Monitoring of other intraoperative vital signs such as PR, SpO2, ECG, and temperature continued throughout the duration of surgery. The patients were also asked about the occurrence and severity of nausea and vomiting after instituting the spinal block. Fluid balance was achieved with warmed 0.9% normal saline. Blood transfusion was commenced if estimated maximum allowable blood loss was exceeded. Hypotension (decrease in BP of more than 20%–30% drop from baseline values or MAP ≤65 mmHg) was treated with IV fluid bolus, and when this was not adequate, 3 mg aliquots of IV ephedrine was given until a BP with MAP of at least 65 mmHg was noted.
The occurrence of PONV was assessed from the initiation of the SAB, during surgery, during patient's stay in recovery room and in the ward for the first 24 h at the 1st h, 3rd h, 6th h, 12th h and at the 24th h. Any retching episode was considered as vomiting. The incidence of PONV was taken as the presence of nausea or vomiting or both. The severity of PONV was graded as 0 (no nausea, no vomiting), 1 (nausea, no vomiting), 2 (vomiting once), and 3 (vomiting two or more episode). Any episode of nausea lasting more than 15 minutes or vomiting was treated with IV cyclizine 50 mg and repeated 4 hourly up to a maximum of 150 mg in 24 h if necessary after treating other possible factors such as hypotension.
The patients' vital signs were monitored and recorded every 10 min in the recovery room and every 30 min in the ward by the nurses. For the purpose of the study, the duration of anesthesia was taken as the period from establishing SAB to discharge from recovery room; while the duration of surgery was taken as time from incision time to last closing-suture was placed. Patients were also questioned about the incidence and severity of PONV in the ward by the researcher during the postoperative visits, and these were recorded.
The total cost of drugs used in each group was taken as the total cost of study drugs plus cost of rescue antiemetic. To evaluate the cost-effectiveness of study drugs, the effectiveness measure in this study was taken as the number of patients free of PONV. The cost of each unit of study and rescue drug was obtained from the hospital pharmacy. The cost evaluation analysis in this study was done using the cost-effectiveness ratio which is defined as the cost per number of patients free of PONV (i.e., cost to keep one patient free of PONV).
Data analysis was done using Statistical Package for the Social Sciences (SPSS ®) version 20.0 SPSS Inc., Chicago, IL, USA. Parametric data such as weight, height, age, duration of surgery, duration of anesthesia, PR, and BP were summarized as means with standard deviation and were analyzed using the unpaired Student's t-test. Categorical data such as ASA classification, incidence of PONV, and PONV severity grading scale were presented as counts or frequencies and analyzed using the Fisher's exact test or Chi-square test. Level of statistical significance was set at P < 0.05.
| Results|| |
The demographic characteristics of the women in both groups were comparable [Table 1]. The mean age (in years) of women in Group A and those in Group B were comparable, with no statistical difference P = 0.058. There was no statistical difference with respect to the mean weight, height and body mass index of the patients in both groups (P = 0.406, 0.652, and 0.439, respectively). The distribution of the patients based on the ASA classification in each group for ASA I and II were comparable. The mean duration of surgery and anesthesia which were also similar for both groups, P = 0.132 and 0.203, respectively.
The incidence of PONV for group A was 10% (n = 5) which was lower than that for Group B, i.e., 12% (n = 6) P = 1.000. All cases of PONV in Group B occurred within the first 3 h of the study period. The incidence of PONV for Group A patients at 0–3 h and 4–24 h were 4% (n = 2) and 6% (n = 3), respectively [Table 2]. The severity of PONV in this study is shown in [Table 3]. Patients in Group B had a score of 1 and 2. There were four patients who had nausea only (score of “1”) and two patients with one episode of vomiting (score of “2”). On the other hand, a severity score of one was observed for patients in Group A (i.e., five patients had only episodes of nausea without vomiting) with P = 0.346. No woman in the ondansetron group required the use of the rescue antiemetic agent while two women (4%) in Group B were given a single dose of cyclizine with good response, P = 0.093.
|Table 2: Incidence of postoperative nausea and vomiting in each group in the first 24 h, at 0-4 h, and at 4-24 h|
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|Table 3: Severity of postoperative nausea and vomiting, the use of rescue antiemetic in each group, the number of patients with multiple episodes of postoperative nausea and vomiting|
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The cost-effectiveness ratios for both groups are shown in [Table 4]. The average direct cost per patient for using metoclopramide plus dexamethasone (Group B) was ₦60 while that for ondansetron (Group A) was ₦160. The total cost of rescue antiemetic used in Group B was ₦2000 whereas none was used in Group A. Therefore, the total amount spent on drugs during the study for each group was ₦8000 and ₦5000 for Group A and B, respectively. The cost-effectiveness ratio based on the number of women completely free of PONV in each group was higher at ₦177.78 for Group A compared to ₦113.63 for Group B.
| Discussion|| |
The low incidence of PONV in the ondansetron group of 10% was not unexpected because IV ondansetron is considered the standard for prophylaxis against nausea and vomiting. The study also showed that ondansetron was better at preventing vomiting than nausea which is consistent with the findings from a quantitative systemic review done by Tramèr et al. Some other studies have observed a similar incidence of PONV as reported by this index study.
However, Olatosi et al. reported a higher incidence of PONV with IV ondansetron when they compared ondansetron, promethazine, and placebo for women who had major gynecological surgeries under general anesthesia. The use of general anesthesia with nitrous oxide could account for the high incidence of nausea and vomiting observed in their study. The greater antiemetic effect of ondansetron as against its antinausea effect observed in the index study could also be seen in this group of patients.
In addition, a higher incidence of PONV was reported by Lee et al. They compared the prophylactic antiemetic effect of IV ramosetron and IV ondansetron. In addition, their patients received fentanyl-based IV patient-controlled analgesia in the postoperative period. Although all the patients had gynecological surgery and received similar doses of ondansetron as in the index study, the use of general anesthesia and postoperative opioids could account for the high incidence of PONV.
The incidence of PONV among the patients who had a combination of metoclopramide and dexamethasone is similar to other studies.,, All the patients who experienced PONV had only nausea which occurred mostly in the first 3 h of their study period. The probable reason for the similarity in the incidence of nausea may be due to the use of a similar dose of IV metoclopramide and dexamethasone (i.e., 10 mg and 8 mg, respectively).
Some studies had reported a higher incidence of PONV for patients who received metoclopramide–dexamethasone combination as in the index study but under general anesthesia., These higher incidences of PONV following the use of a combination of metoclopramide and dexamethasone is not unexpected as the use of general anesthesia and nitrous oxide increases the risk for PONV compared to the use of regional anesthesia.
Our findings contradict those of Awad et al. who reported that ondansetron was more effective than a combination of metoclopramide and dexamethasone as antiemetic prophylaxis. While they studied PONV in patients (both male and female) who had laparoscopic cholecystectomy under general anesthesia, our patients were all females who had myomectomy under spinal anesthesia. A SAB lowers the risk for PONV due to the use of fewer emetogenic drugs compared to general anesthesia.
Although the cost per PONV free patient was lower for the combination of metoclopramide and dexamethasone group than that for ondansetron group, cost-effectiveness should not be assessed solely as the cost of the drugs. Other factors need to be considered. For instance, in the case of PONV, the cost of nursing care, cost of consumables, the cost of rescue antiemetic, and prolonged hospital stay must be taken into consideration.
Previously, Launois et al. assessed the cost of treatment of adverse event, personnel cost (doctor and nursing staff) and cost of materials such as kidney basins, gloves, and draw sheets among others. On the other hand, McCall et al. assessed only drug acquisition cost and gave a justification that other cost associated with drug administration such as syringes; IV tubing is identical in both study groups.
| Conclusion|| |
Metoclopramide–dexamethasone combination had comparable clinical effectiveness and lower cost-effectiveness compared with ondansetron as a prophylactic antiemetic for myomectomy under SAB.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]