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Prophylatic efficacy of dexamethasone, ketamine and dexmedetomidine against intra- and postoperative nausea and vomiting under spinal anesthesia

1 Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak, Iran
2 Department of Gynecology, Arak University of Medical Sciences, Arak, Iran
3 Students Research Committee, Arak University of Medical Sciences, Arak, Iran

Date of Submission09-Apr-2018
Date of Decision30-May-2018
Date of Acceptance21-Aug-2018

Correspondence Address:
Esmail Moshiri,
Department of Anesthesiology and Critical Care, Arak University of Medical Sciences, Arak
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/fjs.fjs_37_18


Introduction: This study aims to compare the prophylactic effects of dexamethasone, ketamine, and dexmedetomidine versus normal saline on intra- and postoperative nausea and vomiting (PONV) associated with cesarean section (CS) under spinal anesthesia.
Materials and Methods: A double-blind prospective clinical trial was performed on 140 patients scheduled for elective CS and was assigned randomly to four groups. The first group received 20 cc normal saline; the second group received dexamethasone at a dose of 0.1 mg/kg; the third group received ketamine at a dose of 0.5 mg/kg; and the fourth group received IV dexmedetomidine (1 μg/kg). Nausea and vomiting score was measured by visual analog scale and sedation levels by Ramsay sedation scale (RSS).
Results: There was a significant difference among the four groups in PONV scores immediately after and 1, 2, 3, and 4 h following administration of the drug (P = 0.001). Nausea and vomiting score was the lowest in the dexmedetomidine group. Significant differences were observed in Ramsey score at the 10th–110th min following administration, and the dexmedetomidine group had a higher RSS than the other groups. The incidence of metoclopramide intervention in three experimental groups is comparable. Heart rate (HR) and mean blood pressure show decreasing trend following spinal anesthesia in dexmedetomidine group.
Conclusion: The tested groups (dexamethasone, dexmedetomidine, and ketamine) all present a lower incidence of nausea and vomiting than the placebo group. In addition, dexmedetomidine provides the best efficacies in the reduction of nausea and vomiting but is more liable in lowering blood pressure and HRs. We recommend that dexmedetomidine is the drug of choice in decreasing nausea and vomiting for patients undergoing CS with spinal anesthesia.

Keywords: Cesarean section, dexamethasone, dexmedetomidine, ketamine, nausea and vomiting

How to cite this URL:
Modir H, Moshiri E, Kamali A, Shokrpour M, Shams N. Prophylatic efficacy of dexamethasone, ketamine and dexmedetomidine against intra- and postoperative nausea and vomiting under spinal anesthesia. Formos J Surg [Epub ahead of print] [cited 2019 Feb 16]. Available from: http://www.e-fjs.org/preprintarticle.asp?id=250869

  Introduction Top

Cesarean section (CS) with spinal anesthesia has attracted much attention in recent years and is now a common surgical practice.[1],[2] Intra- and postoperative nausea and vomiting (IONV and PONV) can be considered the most common problems observed during CS under spinal anesthesia,[3],[4],[5] which may occur during or after birth and may affect the health status of the mother and the newborn.[6] PONV can also lead to critical complications such as airway obstruction, aspiration pneumonia, and wound dehiscence.[7],[8] Nausea and vomiting can result from a number of underlying causes including progesterone-induced decrease in lower esophageal tone, increased intragastric pressure,[4] hypotension due to sympathetic block,[9] reduced cardiac output, exteriorization of the uterus, visceral stimulation, and the use of opioids.[1] Due to the complex pathophysiology, the physicians are faced with many challenges how to prevent and treat PONV; they have tried a wide range of drugs including serotonin and dopamine-receptor antagonists, corticosteroids, antihistamines, sedatives, and anticholinergics.[6],[10],[11]

Dexamethasone is a medication used to prevent nausea and vomiting, with an unknown mechanism, but it is likely to inhibit the prostaglandins that reduce PONV.[12],[13] Visceral pain and vagal stimulation may be the most important mechanisms involved in inducing nausea and vomiting.[9] Therefore, ketamine can prevent the incidence of spinal anesthesia-induced hypotension due to its unique central sympathomimetic, vagolytic, and analgesic properties,[14] which are assumed to reduce the incidence of nausea and vomiting.[15] Dexmedetomidine is an alpha2-adrenergic agonist widely used because of its anxiolytic, sedative, analgesic, sympatholytic, and hemodynamic-stabilizing properties. The intraoperative use of dexmedetomidine can reduce restlessness and has a favorable recovery. It also reduces postoperative pain without hemodynamic effects, and thus, it can prevent PONV.[16] Low doses of dexmedetomidine have been shown in numerous studies to reduce PONV.[17],[18],[19] Since no studies have been designed to compare the efficacy of three drugs in controlling IONV and PONV, this study was aimed to compare the effects of dexamethasone, ketamine, and dexmedetomidine with those of normal saline on IONV and PONV associated with CS under spinal anesthesia.

  Materials and Methods Top

This study was a randomized double-blind prospective clinical trial, with 140 patients undergoing CS under spinal anesthesia. Patients were enrolled according to the inclusion and exclusion criteria after signing a consent form and then randomly assigned preoperatively to four groups receiving ketamine, dexamethasone, dexmedetomidine, and placebo, respectively. Random assignment was conducted by block random allocation method. This project is registered in Iranian Clinical Trail Center by IRCT2016091320258N10 code. Moreover, the ethical committee of Arak University of Medical Sciences approved this project IR.ARAKMU.REC.1395.181

The inclusion criteria were singleton pregnancies, age 18–35 years, elective CS, and ASA physical status I–II. Exclusion criteria were including all patients who taken general anesthesia for surgery (due to failure of spinal anesthesia), needs to opioids after childbirth, body mass index (BMI) >35, below 18 years and above 35 years of age, evidence of intrauterine growth retardation, any antiemetic treatment within 24 h before surgery, a history of motion sickness, gastrointestinal disease, allergy to the study drugs, nausea and vomiting before clamping the umbilical cord, and dissatisfied patients.

Demographic information, blood pressure, heart rate (HR), and arterial oxygen saturation were recorded, and then a 20 cc/kg Ringer's solution was infused to all patients. Spinal anesthesia was performed with a 27-gauge Quincke needle at the L4–L5 intervertebral space, and a fixed dose of 15 mg of hyperbaric bupivacaine 0.5% (3 ml; AstraZeneca) was injected after ensuring that the needle was positioned in the subarachnoid space and the cerebrospinal fluid was excreted. Patients were immediately placed in the supine position and supplemented with oxygen 5–6 L/min through facemask. Before surgery, with a 20-gauge needle pinprick was performed in the midaxillary line and surgery was started after ensuring the appropriate level of sensory block (T4–T6). A decrease in systolic blood pressure (more than 20% below baseline) and/or systolic blood pressure <90 mmHg was recorded as hypotension, and the following routine treatments were used as follows: semiTrendelenburg position, increasing intravenous fluid administration, or administering intravenous ephedrine (5–10 mg). After the delivery of the newborn, 20 units of oxytocin were administered as an infusion in the serum.

After umbilical cord clamping, patients were assigned to four groups with random allocation. The first group received 20 cc of normal saline; the second group received dexamethasone (4 ml/2 mg; Alborz Darou Co.) at a dose of 0.1 mg/kg solution in normal saline, and a total volume of 20 ml was administered. The third group received ketamine (50 ml/mg, Hospira) at a dose of 0.5 mg/kg solution in normal saline with a total volume of 20 ml, and the fourth group received dexmedetomidine (100 μg/ml Hospira) at a dose of 0.5 μg/kg solution in normal saline with a total volume of 20 ml for 10 min. The frequency and severity of nausea and vomiting were recorded on the basis of a visual analog scale (VAS) after umbilical cord clamping for up to 4 h after surgery; and blood pressure, HR, and arterial oxygen saturation were recorded every 5 min until discharge from recovery room.

The VAS consists of a 10 cm ruler extending longitudinally between 0 and 10, which represent “no nausea” and “the most severe possible condition,” respectively.[20] Patients are asked to mark their level of nausea and vomiting, expressed as the distance from the zero point, on the ruler. Ten mg of metoclopramide solution in 10 cc of normal saline was slowly injected to all the groups to control vomiting, if needed (the total dose of metoclopramide was also recorded for all patients). To assess the level of sedation of the patient, the Ramsay sedation scale (RSS) was used and the sedation score was recorded just before the injection of the study drugs and then every 10 min until discharge from recovery room.[21],[22] It should be noted that the second project executive, who was unaware of the grouping assignment, recorded the data.

The RSS is both reliable and valid and a clinically derived scale with high correlation with the Richmond Agitation-Sedation Scale for assessing agitation and sedation.[23] The scoring of RSS is varied between 1 and 6 including as 1 – anxious, agitated, and restless, 2 – sedation oriented and tranquil, 3 – sedation response to commands, 4 – brisk response to light glabellar tap, 5 – sluggish response to light glabellar tap, and 6 is deep sedation with no response.[24]

Finally, data analysis conducted using SPSS (Version 20.0. IBM Corp., Armonk, NY) software. Comparing quantitative variables including VAS, RSS, HR, mean blood pressure (MBP), and SaO2 among groups conducted the analysis of variance test. When the ANOVA test was significant, the Tukey post hoc test was used to determine significance level for two by two comparisons. Moreover, the assessing the trend of VAS and other variables performed by repeated measurement ANOVA.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.

  Results Top

The mean age of participants in our study was 25.6 ± 3.8 years, and there was no significant difference among groups regarding age (P ≥ 0.05). The mean of BMI in all patients was 28.9 ± 3.6 kg/m2 and showed some difference among studied groups (P = 0.03). The BMI of dexmedetomidine was higher than the placebo group (P = 0.043), while the other groups did not differ significantly (P > 0.05).

Based on our results, the VAS scores from low-to-high were the dexmedetomidine group, dexamethasone group, ketamine group, and placebo group [Figure 1]. There is a significant difference in VAS scores between the dexmedetomidine group and the other groups (P < 0.001). The VAS scores in dexamethasone group and ketamine groups showed of a similar trend but no statistical difference between the dexamethasone group and placebo group. In addition, the VAS scores gradually decreased in each time interval regardless of the patient groups [Figure 1].
Figure 1: Changes of intra- and postoperative nausea and vomiting scores (visual analog scale) for pregnant women at different time points following spinal anesthesia and cesarean section for pregnant women in the four groups of dexamethasone, dexmedetomidine, ketamine, and placebo

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Based on the analysis of RSS data [Table 1] and [Figure 2], there was no significant difference in initial RSS between the placebo group and the other three groups. Significant differences were observed in Ramsey score at the 10th–110th min following administration of the study drugs. The Tukey post hoc test showed that the dexmedetomidine group (and then the ketamine group at the 10th min and the 60th–110th min) had a higher RSS than the other groups. The dexmedetomidine group, as shown in [Table 1], has a higher RSS than the other groups.
Table 1: Comparison of Ramsay Sedation Scores of the pregnant women at different time points following spinal anesthesia and caesarean section in the 4 groups of dexamethasone, dexmedetomidine, ketamine and placebo

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Figure 2: Changes of Ramsay sedation scores at different time points following spinal anesthesia and cesarean section for pregnant women in the four groups of dexamethasone, dexmedetomidine, ketamine, and placebo

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According to the analysis of variance, we observed that a significant difference among four groups at all times except for initial HR [Table 2]. The Tukey post-hoc test showed that the mean of HR was lower in dexmedetomidine group than other groups (P < 0.05) except at initial HR (P = 0.064).
Table 2: Comparison of heart rates of pregnant women at different time points following spinal anesthesia and caesarean section in the four groups of dexamethasone, dexmedetomidine, ketamine and placebo

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Repeated measurement analysis showed that no significant trend was observed in the mean of HR in the placebo group (P = 0.0929). However, the trend of HR in all three-intervention groups was decreasing (P < 0.005).

According to [Table 3], there were significant differences in MBP among four groups in all times (P < 0.05) except at the initial, 75th, 85th, and 95th min following administration. The Tukey post-hoc test showed that in all time, the lowest blood pressure level in the dexmedetomidine group (P < 0.05). The trend of blood pressure based on repeated measurement test was not significant in all groups except in the placebo group (P = 0.004) and dexmedetomidine group (P = 0.001).
Table 3: Comparison of blood pressure of pregnant women at different time points following spinal anesthesia and caesarean section in the four groups of dexamethasone, dexmedetomidine, ketamine and placebo

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The analysis of variance showed that there was a significant difference in SaO2 [Table 4] among four groups at times 35th–75th and at 95th min following administration (P < 0.001). In these times, the SaO2 in the placebo group was higher than in the other groups based on the Tukey post-hoc test. The repeated measurement test showed that only the placebo group has an increasing trend in SaO2 (P < 0.001). Nevertheless, the trend of SaO2 in other groups was not significant (P > 0.05).
Table 4: Comparison of oxygen saturation percentage of pregnant women at different time points following spinal anesthesia and caesarean section in the four groups of dexamethasone, dexmedetomidine, ketamine and placebo

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Adverse effects

Two of patients in placebo group need to metoclopramide for control of nausea and vomiting. However, no significant difference was observed in need to metoclopramide among the groups (P = 0.107). In addition, the Apgar score of newborns at the 1st and 5th mins was not significantly different in all groups (P = 0.178).

  Discussion Top

Based on the results, the VAS scores of nausea and vomiting ranking from low to high present as dexmedetomidine, dexamethasone, ketamine, and placebo, and the tendency keeps the same ranking. The Ramsey scores also showed dexmedetomidine >dexamethasone >ketamine >placebo at initial time interval and with similar trend after drugs injection. Therefore, using single-dose dexmedetomidine in pregnant patients undergoing CS with spinal anesthesia provides a low incidence of nausea and vomiting and adequate sedation.

In a meta-analysis study, the efficacy of dexmedetomidine for prophylaxis against nausea and vomiting after general anesthesia was evaluated and showed that dexmedetomidine could reduce the incidence of nausea and vomiting in comparison to placebo significantly. Dexmedetomidine is an α2-adrenergic agonist. The antiemetic effect may be mediated through its inhibition of catecholamine by parasympathetic tone but may induce its side effects of bradycardia and hypotension.[25] The results of this study were consistent with our study where dexmedetomidine could better reduce nausea and vomiting as compared to other groups. Nevertheless, the results of another study showed that dexamethasone did not reduce nausea and vomiting.[26] and therefore were inconsistent with our study. Some difference was existing between Bakri et al., and our study that difference in outcomes could be attribute to the difference in the type of surgery, the duration of patient monitoring, observation, and the patients gender of two studies. The study participants in our work were female, whereas in Bakri et al. study, both genders were participated. In addition, a study among 86 patients at Sudan in 2015 has similar results and showed that dexmedetomidine and dexamethasone were effective antiemetic drugs in reducing the incidence and severity of PONV after laparoscopic cholecystectomy. Moreover, patients in the dexmedetomidine group reported less pain in the first 24 h after surgery.[27]

The hemodynamic effect of dexmedetomidine was assessed in other studies and showed that dexmedetomidine has better effect in controlling of HR, MBP, and SaO2 than other antiemetic drugs such as lidocaine, alfentanil, and propofol.[28],[29],[30],[31]

Another study evaluates the IONV effect on 308 German patients in four groups: Group 1, received either no prophylaxis; Group 2, received tropisetron and metoclopramide; Group 3, received dimenhydrinate and dexamethasone; and Group 4, received only tropisetron. The results showed that, although all prophylactic drugs could contribute significantly to the reduction of IONV, the prophylactic treatment with tropisetron and metoclopramide was more effective than the other groups.[32] Consistent with this study, our study showed dexmedetomidine and dexamethasone were effective in reducing nausea and vomiting, but tropisetron and metoclopramide may be another good choice for prophylaxis of INOV and PONV.

In a study on 2029 Egyptian patients, the effect of ketamine on IONV was assessed during elective CS under spinal anesthesia and showed that IV infusion ketamine (0.5 mg/kg for 20 min) could significantly reduce the incidence of PONV and hypotensive episodes[15] that was consistent with our study. Another study showed no statistical difference in prophylactic effect of ondansetron and dexamethasone on PONV after Intrathecal Meperidine in Women Scheduled for Elective CS. So that dexamethasone and ondansetron could equally reduce the incidence of nausea, vomiting, and itching induced by intrathecal injection of meperidine.[33] In our study, dexamethasone immediately reduced the incidence of nausea and vomiting than placebo but was more effective with dexmedetomidine. In another study, the effectiveness of metoclopramide, dexamethasone, and propofol compared in control of IONV during spinal anesthesia for emergency CS and found similar antiemetic effects of propofol and metoclopramide in 144 patients. This study concluded that the lowest incidence of IONV was in propofol group and the highest in the dexamethasone group, and propofol may also be a good choice for prophylaxis of INOV and PONV.[34]

This study has some limitations. It was not designed to assess the effect of mixture of dexamethasone and ketamine in IONV and PONV in after cesarean delivery. Moreover, the patient's satisfaction regarding pain did not evaluate in our study. We plan to look at this in further studies and suggest that do future studies with more than sample size.

  Conclusion Top

Using all three drugs could improve nausea and vomiting in patients. Nevertheless, dexmedetomidine has a greater effect in reducing nausea and vomiting and was more effective in reduce blood pressure and HR. However, dexamethasone and ketamine were same in the next rank. Therefore, dexmedetomidine is recommended to prevent nausea and vomiting in patients scheduled for CS, but anesthesiologists should be aware of side effects such as hypotension and bradycardia. In the end, a long-term regular follow-up is recommended, and also, studies for patients with conditions other than pregnancy are suggested.


This study is based on part of the author's thesis (with the Code of Ethics: IR.ARAKMU.REC.1395.181), registered in the Iranian Registry of Clinical Trials with the registration number IRCT2016091320258N10. The researchers would like to thank the Deputy of Research of Arak University of Medical Sciences, the Clinical Research Center of Valiasr hospital in Arak and all those who participated and helped us in this study.

Financial support and sponsorship

Arak University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4]


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