|Year : 2019 | Volume
| Issue : 1 | Page : 57-62
Comparing the efficacy of dexmedetomidine, dexamethasone, and metoclopramide in postoperative nausea and vomiting of tympanomastoidectomy surgery: A double-blind randomized clinical trial
Hesameddin Modir1, Esmail Moshiri1, Alireza Kamali1, Atefeh Khalifeh2, Abolfazl Mohammadbeigi3
1 Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak, Iran
2 Department of Student Research Committee, Arak University of Medical Sciences, Arak, Iran
3 Research Center for Environmental Pollutants, Qom University of Medical Sciences, Qom, Iran
|Date of Web Publication||22-Aug-2019|
Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: Postoperative nausea and vomiting (PONV) are of the most common complications after anesthesia and surgery that affects 20%–30% of patients. This study aimed to examine the efficacy of dexmedetomidine (DEXM), dexamethasone (DEXA), and metoclopramide (METO) on the reduction of PONV after tympanomastoidectomy. Materials and Methods: In a clinical trial study, 90 patients who undergoing tympanomastoidectomy surgery were assigned to DEXM (1 μg/kg/intravenous [IV]), DEXA (0.1 mg/kg/IV), and METO (0.15 mg/kg/IV) groups by block randomization method. The initial vital signs and vomiting score as responses to treatment were assessed using visual analog scale through 24 h (6, 12, 18, and 24) after the end of surgery. The vomiting score varied from 0 (no vomiting) to 100 (the worst possible vomiting). One-way analysis of variance (ANOVA), paired t-test, and repeated measure ANOVA was used for statistical analysis in SPSS version 12.5 (SPSS Inc., Chicago, IL, USA). Results: The incidence of PONV was 10%, in DEXM 0%, DEXA 6.7%, and 23.3% in METO. Vomiting score is much lower for the DEXM than for the other two groups, and rather rapidly declined 18 h after the intervention. The difference of time 6–24 was significant among three groups (P < 0.05). A greater reduction observed in vomiting total scores in DEXM group compared to other groups at time 18–24 as well as time 6–24. Conclusion: DEXM, DEXA, and METO are effective drugs for control of PONV after tympanomastoidectomy surgery. However, the reduction effect of DEXM and DEXA in vomiting total scores was higher than METO.
Keywords: Antiemetic, dexamethasone, dexmedetomidine, nausea, vomiting
|How to cite this article:|
Modir H, Moshiri E, Kamali A, Khalifeh A, Mohammadbeigi A. Comparing the efficacy of dexmedetomidine, dexamethasone, and metoclopramide in postoperative nausea and vomiting of tympanomastoidectomy surgery: A double-blind randomized clinical trial. J Pharm Negative Results 2019;10:57-62
|How to cite this URL:|
Modir H, Moshiri E, Kamali A, Khalifeh A, Mohammadbeigi A. Comparing the efficacy of dexmedetomidine, dexamethasone, and metoclopramide in postoperative nausea and vomiting of tympanomastoidectomy surgery: A double-blind randomized clinical trial. J Pharm Negative Results [serial online] 2019 [cited 2019 Sep 23];10:57-62. Available from: http://www.pnrjournal.com/text.asp?2019/10/1/57/265145
| Introduction|| |
Tympanomastoidectomy is two surgical procedures including tympanoplasty and mastoidectomy that often conducting together on a patient's ear to control chronic infection and restore hearing., Tympanomastoidectomy is a convenient and safe way to correct the hear impairment as an appropriate approach for the successful removal of cholesteatoma in the middle ear, attic, and mastoid cavity., This method has a minimum invasion, and damage to the area will not be sustained throughout the surgery. Tympanomastoidectomy operation is performed under general anesthesia with endotracheal tube placement. Postoperative nausea and vomiting (PONV) are the most common complications after surgery and the most important peri-operative concern for patients., The PONV incidence in tympanomastoidectomy is not higher than other surgeries, but the ENT operations are a risk factor for PONV.,
PONV as an important clinical problem that occurring within 24 h of surgery affects 20%–30% of patients., However, PONV is one of the most common complications of anesthesia in patients with laparoscopic surgery and occurring to 70% in some cases. The PONV is associated with pain and increase the electrolyte imbalance, dehydration, tracheal aspiration of vomitus acid-base imbalance, anxiety, and wound dehiscence., PONV contributes to most dissatisfactory outcomes after the anesthesia for surgery, increasing the hospital stay beside longer postoperative recovery and casting the financial burden with medical waste.
Several drugs have been used for control and prevention PONV after anesthesia and different types of surgery., Dexmedetomidine (DEXM), dexamethasone (DEXA), and metoclopramide (METO) are the most drugs that used during anesthesia for surgery in Iran.,, The aim of this study is to examine the efficacy of these three major drugs on the reduction of PONV after the Tympanomastoidectomy.
| Materials and Methods|| |
A total of 90 patients who are undergoing elective tympanomastoidectomy with general anesthesia were included in the current clinical trial. A single surgeon between January 2015 and May 2016 performed all the surgeries. The project had ethical approval from the University Ethics Committees in which the study was conducted. Moreover, this study is registered in the Iranian Clinical Trail center by IRCT2016092629993N1 code. Participants completed the written informed consent before random allocation to study groups. Sample size calculation conducted based on the results of our recent works and by applying the Cochrane formula for comparing two proportions. The prior proportion of PONB in two groups estimated based on a pilot study and was equal to 4% and 31% in DEXM and MET groups. Type one error (α) and power of study (1-β) were considered as 0.05 and 0.80, respectively. Therefore, the minimum sample size for each group calculated as 27.
Inclusion criteria for enrollment included all 20–50-year patients with ASA Class I-II or candidates presenting for elective tympanomastoidectomy. Patients who were pregnant, unable to understand and complete the questionnaires, confirmed allergy to used antiemetic drugs or local anesthetics, use of opioids for pain relief, affecting to nausea and vomiting treatment 48 h before surgery and BMI higher 35 kg/m2 were excluded. We have not placebo/control group due to ethical issues because according to Apfel risk score if a patient be at risk of nausea and vomiting, we cannot deprive him from medicine.
After recruitment of subjects, the eligible patients were randomly allocated to 1 of 3 groups including DEXM (1 μg/kg/intravenous [IV]) (n = 30), DEXA (0.1 mg/kg/IV) (n = 30), and METO (0.15 mg/kg/IV) (n = 30) groups. The flow chart of assignment of subjects to studied groups is depicted to [Chart 1]. Random allocation conducted by random permuted block method and 15 blocks was selected randomly, and the block size considered six.
Patient demographics including gender, age, history of nausea and vomiting, history of medication, blood pressure, heart rate, body mass index (BMI), and oxygen saturation (SaO2) were collected. Before the surgery, all patients were given a description of the visual analog scale (VAS).
The anesthesia protocol was the same for three groups. Anesthesia was induced by 2 μg/kg/IV fentanyl, 0.4 mg/kg/IV atracurium, and 2.5 mg/kg/IV propofol and maintained with oxygen 100% combination with isoflurane 1% minimum alveolar concentration. Atracurium 7 μg/kg/IV plus propofol 100–150 μg/kg/min/IV and fentanyl 5–7 μg/kg/h/IV were given as analgesic top up during maintenance of anesthesia for the achievement to bispectral index (BIS) 40.
For matching of the anesthesia depth in groups was used a BIS monitoring tool for assessing the depth of anesthesia. The number of 100 is sign of complete consciousness, and 0 shows the isoelectric smooth line. The range 40–60 indicates moderate-to-deep anesthesia, optimizing the depth of the case.
The initial vital signs including blood pressure and heart rate were measured: (1) during the operation and at the time before administration of the medication (T0), (2) 5 min after the administration of the medication (T1), (3) 30 min after the administration of the medications (T2), (4) 5 min after the removal of the patient's tracheal tube (T3), (5) entrance to Recovery (T4). Ten minutes after tracheal intubation, the patients in Group A were administered IV DEXM 1 μg/kg/IV, and in Group B, DEXA 0.1 mg/kg/IV and Group C METO 0.15 mg/kg/IV. In each group, the administered volume of the intervention was adjusted to 4 mL by mixing normal saline. The same surgical team performed all the surgical interventions, and a single surgeon performed all surgeries. Patients were visited to evaluate their response to treatment using the VAS through 24 h (6, 12, 18 and 24) after the end of surgery. Nausea and vomiting intensity scores were measured with a VAS from 0 (no vomiting) to 100 (the worst possible vomiting). If the VAS, nausea and vomiting score assessed was >60 or individuals demand for antiemetic medicine, 4 mg/IV Ondansetron as antinausea was injected intravenously.,
Statistical analysis was performed using SPSS version 12.5 (SPSS Inc., Chicago, IL, USA). Data are presented as mean ± standard deviation or percent. Patients' characteristics such as baselines, age, and BMI were compared with One-Way analysis of variance (ANOVA) with Sidak correction. For the comparison of the treatment effects, the repeated measure ANOVA test was used. Regarding the comparison of the mean differences of nausea/vomiting score changes between Groups I, II, and III, the one-way ANOVA test was used. The results were considered statistically significant at P < 0.05 level.
| Results|| |
The mean of age and BMI in participants was 36.03 ± 7.62 years and 26.76 ± 4.12 kg/m 2, respectively. Patient demographic and baseline data were comparable between two groups [Table 1]. There were no significant differences in age, BMI, heart rate mean blood pressure, oxygen saturation, and duration of surgery among groups based on ANOVA in baseline measurements. Moreover, the Chi-square test showed that the sex distribution, smoking, vomiting history, and history of motion sickness were same among three groups.
|Table 1: Comparing the demographic baseline characteristics of patients in three groups|
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[Figure 1] shows the marginal means over the four times for the three study groups. Results show that vomiting score is much lower for the DEXM than for the other two groups, and rather rapidly declined 18 h after surgery. The linear trend of interaction indicates that the linear trend is different among groups.
|Figure 1: The marginal means (difference) over the four times for the three study groups including dexmedetomidine, dexamethasone and metoclopramide|
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The overall incidence of PONV was 10% (9/90). This rate in DEXM was 0%, DEXA 2 (6.7%) and in METO was 7 (23.3%). Need to antiemetic drug in DEXA was 12 h after surgery in all 6.7% of patients of DEXA while this rate was 16.7% in METO group. Moreover, need to antiemetic drug in two patients of METO group (6.7%) was observed 18 h after surgery. The need to antiemetic drug was statistically significant among groups. By the end of the trial, 7 patients in METO group, 2 in DEXA, and 0 in DEXM group needed to treatment against vomiting, which was significantly different (χ2 = 8.97, P = 0.004). Repeated measure ANOVA by adjusting the effects of covariates showed a significant effect for time* group interaction (Greenhouse–Geisser corrected: F =3.406, P = 0.01).
ANOVA was used to comparing the mean of VAS for vomiting total scores through 24 h (6, 12, 18, and 24) after the end of surgery among three study groups [Table 2] and showed that the mean of VAS was significantly different among groups (P< 0.01). Moreover, repeated-measure ANOVA showed a decreasing trend in VAS for vomiting total scores in all groups [Table 2] and [Figure 2].
|Table 2: Comparing the mean of visual analogue scale for vomiting total scores in different times after surgery among dexmedetomidine, dexamethasone and metoclopramide groups|
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|Figure 2: The reduction trend in vomiting total scores in the dexmedetomidine, dexamethasone and metoclopramide groups at different time after surgery|
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The paired t-test was used to compare the difference in vomiting total scores through 24 h after surgery and showed that the differences were statistically significant among three groups (P< 0.05). However, the One-Way ANOVA test showed significantly greater reduction in vomiting total scores in the DEXM group compared to the other groups at 18–24 h after surgery as well as 6–24 h after surgery as the outcomes of this trial [Table 3] and [Figure 2]. However, other consequences in patients such as oral intake, early ambulation, and use of opioids and other analgesics among the groups were not significant, and all three groups were similar (P > 0.05).
|Table 3: Comparing the reduction in vomiting total scores (difference) in the dexmedetomidine, dexamethasone and metoclopramide groups at different time after surgery|
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| Discussion|| |
According to the results of the current study, all three study drugs including DEXM, DEXA, and METO have a reduction effect in vomiting score of patients after tympanomastoidectomy surgery are effective for PONV. However, after adjusting the effects of covariates, it was showed that only a significant interaction effect for time and study group. Our analysis showed a greater decreasing effect in vomiting score in the DEXM and DEXA groups compared with the METO after Tympanomastoidectomy. The vomiting scores were much lower in DEXM in all times and rather rapidly declined 18 h after the surgery.
A recent study in 2017 showed that DEXM used by dose of 3 μ in cesarean surgery provides better intraoperative somato-visceral sensory block characteristics and postoperative analgesia and has not any effect on neonatal Apgar scores or other side effects and stress response for mother. Moreover, the effect of using DEXM (1 μg/kg over 10 min) comparing to remifentanil at an initial target effect-site concentration of 4 ng/ml during the induction of anesthesia assessed for the first 24 h in 2 time periods (0–2 h and 2–24 h) by Choi et al. They showed that at the 2 times, the incidence and severity of PONV in DEXM group were significantly lower than other group and consequently the need for using antiemetic drugs was significantly lower in DEXM group. Moreover, DEXM was superior regarding to postoperative pain relief. DEXM also was appropriate drug for premedication of patients undergoing electroconvulsive therapy with high patient' satisfaction. Moreover, it could have a myocardial protection effects in percutaneous coronary interventional patients.
The overall incidence of PONV in our study was 10%, and it is calculated 0% for DEXM, 6.7% for DEXA and 23.3% for METO. However, the antiemetic effect of DEXM and DEXA was statistically lower than METO. Similar results observed in other studies. In Apipan et al. study the incidence of PONV after general anesthesia for oral and maxillofacial surgery was estimated 25.26%. Age lower 30 years, history of PONV and/or motion sickness, and anesthesia duration >4 h were the most predictors of PONV based on the multiple regression model. As the same study, the overall incidence of nausea was calculated in Entezariasl et al. study 22% in the recovery room as 44% for placebo, 20% in METO, 16% in DEXA, and 8% in the combination of METO and DEXA. Moreover, the vomiting incidence was lower and estimated 4% for both METO and DEXA.
We used 0.1 mg/kg/IV (8 mg) DEXA in this study, and our results showed that lower effect in preventing PONV than DEXM but better effect than METO. The results of a meta-analysis showed that a 4–5 mg dose of DEXA is effective in reduction of PONV as the same of 8–10 mg dose with or without the combination of other drugs. Another meta-analysis in women with cesarean delivery and abdominal hysterectomy after receiving neuraxial morphine showed that DEXA is an effective antiemetic drug and decrease the PONV.
This study could compare the efficacy of three most common antiemetic drugs in Iran including DEXM, DEXA, and METO by a scientific manner. However, we cannot compare the PONV effect of these drugs with control/placebo due to ethical consideration of Apfels scoring or with a combination of drugs. Future studies suggest to assess these limitations of the current study.
| Conclusion|| |
According to our results, DEXM, DEXA, and METO are effective drugs for control and prevention of PONV after tympanomastoidectomy. However, the reduction effect of DEXM and DEXA in vomiting total scores was higher than METO and can be used more in tympanomastoidectomy. Furthermore, the need to antiemetic drugs in DEXM group was lower and higher in METO group.
Financial support and sponsorship
This study was supported by Arak University of Medical Sciences, Arak, Iran.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]