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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 3  |  Page : 157-161

Haloperidol vs. dexamethasone in lowering postoperative nausea and vomiting and pain in adult after laparoscopy: A randomized, double-blind study


Department of Anesthesiology and Intensive Care, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Date of Submission30-Mar-2022
Date of Decision19-May-2022
Date of Acceptance06-Jun-2022
Date of Web Publication27-Jul-2022

Correspondence Address:
Aldy Heriwardito
Jati Palem No. 20, Jati, Pulo Gadung, Jakarta Timur, DKI Jakarta 13220
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoa.bjoa_101_22

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  Abstract 

Background: The incidence of PONV (Postoperative Nausea and Vomiting) and pain are still one of the most common symptoms of post-surgery and prophylaxis to reduce the event is needed. Therefore, we wanted to know the effectiveness of 1 mg intravenous haloperidol compared to 5 mg intravenous dexamethasone to prevent the occurrence of nausea and vomiting and to control pain in adult patients after laparoscopic surgery. Materials and Methods: Eighty subjects (n = 40 for each group) scheduled for laparoscopic-assisted surgery were enrolled in a randomized double-blind clinical trial. One milligram intravenous haloperidol was given one hour before the end of surgery, while 5 mg intravenous dexamethasone was given right after induction. The occurrence of PONV and VAS pain score were recorded. Results: This study showed a significant difference in the incidence of nausea between haloperidol and dexamethasone at 2–6 hours (5% vs 25%, P = 0.012), 6–12 hours (10% vs 24%, P = 0.012), and 12–24 hours (12.5% vs 60%, P < 0.001) after laparoscopic surgery. The incidence of vomiting after laparoscopic surgery between two groups was not significantly different (P > 0,05). However, haloperidol group resulted in lower VAS pain score at every postoperative period with statistically significant result. Conclusion: The administration of 1 mg intravenous haloperidol is significantly better than 5 mg intravenous dexamethasone to prevent the occurrence of nausea and to lower the pain, but not significantly different to prevent the incidence of postoperative vomiting in adult patients after laparoscopic surgery.

Keywords: Dexamethasone, haloperidol, nausea, pain, vomiting


How to cite this article:
Heriwardito A, Manggala SK, Widhyanti SI, Aristya L. Haloperidol vs. dexamethasone in lowering postoperative nausea and vomiting and pain in adult after laparoscopy: A randomized, double-blind study. Bali J Anaesthesiol 2022;6:157-61

How to cite this URL:
Heriwardito A, Manggala SK, Widhyanti SI, Aristya L. Haloperidol vs. dexamethasone in lowering postoperative nausea and vomiting and pain in adult after laparoscopy: A randomized, double-blind study. Bali J Anaesthesiol [serial online] 2022 [cited 2022 Aug 10];6:157-61. Available from: https://www.bjoaonline.com/text.asp?2022/6/3/157/352399




  Introduction Top


Postoperative nausea and vomiting (PONV) are one of the most common symptoms found after anesthesia and surgery, which can lead to longer length of hospital stay. Laparoscopic surgery has a high risk in developing PONV due to the abdominal wall stretching caused by gas insulation during the procedure.[1] Other factors contributed to PONV are young age, history of motion sickness, anesthesia (opioid or volatile anesthesia administration), and surgery (duration of procedure, dehydration, untreated pain, bowel manipulation).[2] As the minimal invasive surgery keeps on developing, many patients tend to choose laparoscopy rather than open surgery.[3] It leads to an increase of the incidence of nausea and vomiting. Therefore, this research can contribute to give antiemetic choice for patients undergoing minimal invasive surgery. The incidence of PONV after laparoscopy surgery ranging from 46–75%, which is higher than in other surgery. At our hospital as per November 2019, the incidence reached 45%.[4] It caused a prolonged post anesthesia care unit (PACU), leading to more expensive hospital stay costs.

Haloperidol is one of the best alternatives which has several advantages compared to dexamethasone.[5] Haloperidol has a longer duration of action compared to dexamethasone, which will prevent the nausea and vomiting incidence in adult patients for more than 24 hours postoperative. Brettner[6] reported that the incidence of PONV after using haloperidol as the antiemetic was 35%, compared to 50% in dexamethasone group. In addition to the antiemetic effect, both haloperidol and dexamethasone also act as pain control, however, the comparison of its effectivity between both drugs has not been studied.

Due to those considerations, we conducted research to find out the effectiveness of 1 mg intravenous haloperidol compared to 5 mg intravenous dexamethasone to prevent the occurrence of nausea and vomiting also as pain control in adult patients after laparoscopic surgery.


  Materials and Methods Top


This double-blind randomized clinical trial was conducted in January to March 2020 with clinical trial registration number of NCT05246631 dated February 18, 2022. The enrollment diagram was shown in [Figure 1]. Eighty patients aged between 18–65 years old who underwent laparoscopic surgery (gynecology, digestive, or urology surgery), and ASA physical status 1–3 were studied after informed consent was given. The data were obtained after got a permission from ethics committee and written informed consent from the patient.
Figure 1: Enrollment diagram

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Patients with psychological or neurological disorders (routine haloperidol consumption), history of allergic reaction to dexamethasone or haloperidol, diabetes mellitus, and did not give the consent for this research were excluded. Patients which experienced emergency during perioperative period and allergic reaction or side effects from haloperidol consumption were dropped out.

Number of patients assessed for eligibility was 80 with no exclusion. Patients were included consecutively using computer-based randomization, continued with double-blinded random allocation into two groups of 40 patients. Group A consisted of patients given 5 mg intravenous dexamethasone after induction. Group B consisted of patients given 1 mg intravenous haloperidol one hour before the surgery ended. All samples were examined for pre-anesthesia work-up to obtain gender, age, body weight, height, and ASA physical status. After entering the operating room, patients were recorded for standard electrocardiography, non-invasive blood pressure, and pulseoximetry throughout the procedure and intravenous cannula insertion. Patients were given 0.05 mg/kg midazolam for co-induction, followed by 2 mcg/kg fentanyl after one minute. Induction was given three minutes later using 1–2 mg/kg propofol. Endotracheal tube insertion was facilitated with 0.5 mg/kg atracurium. The oxygen-to-air ratio of 1:2 with 2 L/min flow rate and sevoflurane 2 vol% as maintenance were given. The ventilator was set to 8 mL/kg volume control and 12 breaths/min. After surgery, the patients were injected with intravenous analgesia, reversal using 0.04 mg/kg neostigmine, and 0.4 mg atropine every 1 mg of neostigmine.

At the recovery room, the incidence of nausea and vomiting and pain were evaluated. Patients who vomited over 10 minutes post laparoscopy were given 4 mg intravenous ondansetron as rescue antiemetic and could be repeated once. If patients experienced respiratory depression, 6 L/min oxygen using face mask and 0.04 mg intravenous naloxone could be given. Naloxone could be titrated every 1–3 minutes until the respiratory rate reached minimum 12 breaths/min. Visual analog scale (VAS) was measured subjectively by asking the patient to place a mark on the scale that corresponds to their pain for 0–2 hours, 2–6 hours, 6–12 hours, and 12–24 hours postoperative. The patients and researchers were blinded for the intervention until the trial ended. The primary clinical outcomes were the incidence of nausea and vomiting at 0–2 hours, 2–6 hours, 6–12 hours, and 12–24 hours. The secondary outcome was pain score evaluated using VAS.

Data were analyzed using Statistical Package for the Social Science or SPSS® software (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). To test for normal distribution, the Kolmogorov-Smirnov test was carried out. The incidence of PONV was analyzed using Fischer test and Chi-square due to non-normal data distribution. The VAS score was analyzed using independent T-test, presented with mean and standard deviation. A p-value of <0.05 was considered statistically significant.


  Results Top


Eighty patients were eligible to the study, with no exclusion and drop out. The patients were divided into two groups, dexamethasone group and haloperidol group, consisted of 40 patients in each group. All the patients within group were analyzed in this study.

The demographics of two groups were comparable in terms of age, gender, body weight, ASA, Apfel score, duration of surgery, and intraoperative fentanyl dosage [Table 1]. The mean age of haloperidol was older than dexamethasone group (44.53 vs 39.88 years, respectively). Most of the patients were assessed with ASA 2 in both groups. The mean body weight in haloperidol group was 0.65 kg higher than dexamethasone group. The mean operative time in haloperidol group was longer with lower dosage of intraoperative fentanyl.
Table 1: Demographic characteristic

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The incidence of nausea and vomiting after laparoscopy were presented in [Table 2]. The incidence of postoperative nausea on dexamethasone group 2–6 hours (25% vs 5%), 6–12 hours (65% vs 10%), and 12–24 hours (60% vs 12.5%) were significantly higher than haloperidol group, with P < 0.05. The most common side effects of haloperidol consumption are prolonged QT interval, extrapyramidal symptoms, and drowsiness. As for dexamethasone’s side effects are peptic ulcer and immunosuppression. However, in this research, there was no incidence of side effect found in both groups on 24 hours after laparoscopy surgery. This may be due to the low and single dose used for both medications.
Table 2: PONV after laparoscopic surgery

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The visual analog scale (VAS) on both groups was also documented and analyzed to evaluate the effect of haloperidol and dexamethasone towards pain as the secondary outcome [Table 3]. Contrary to the PONV after laparoscopic surgery, patients in dexamethasone group showed higher pain scale compared to haloperidol for all period, with P = 0.017 for 0–2 hours postoperative, and P = 0.000 for 2–6 hours, 6–12 hours, and 12–24 hours postoperative.
Table 3: VAS after laparoscopic surgery

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  Discussion Top


The objective of this study was to compare the effectiveness of 1 mg intravenous haloperidol to 5 mg intravenous dexamethasone to prevent the incidence of nausea and vomiting in adult patients and the effectiveness of the drugs in controlling pain after laparoscopic surgery. The demographic distribution between two groups showed no significant difference; hence, both groups were comparable to each other.[7]

Postoperative nausea and vomiting (PONV) are the most common anesthesiology and surgery complication which left unpleasant experiences for patients, aspirations, prolonged duration of hospitalization, and increased hospital cost. Factors influenced the incidence of PONV were gender, age, BMI, type of surgery, duration of surgery, and opioid administration.

In this research, the incidence of nausea in haloperidol group were 5% at 6 hours, 10% at 12 hours, and 12.5% at 24 hours post laparoscopic surgery. These results were similar to Smith J et al,[5] which showed a low incidence of nausea in patients using haloperidol. It may be caused by the mechanism of action by blocking the dopamine receptor (D2) on central nervous system at chemoreceptive trigger zone (CTZ) and on peripheral nervous system, specifically at receptors alongside the digestive system. Dopamine receptor (D2) were known to have an important role of inducing nausea and vomiting. This mechanism involved adenylate cyclase blockade, thus, there was a decrease in cAMP at the nucleus solitarius tract and postrema.[8],[9] Another factor which may affect the result was within six hours postoperative, the action of drugs that caused nausea and vomiting had started to slow down and allowed the haloperidol to effectively suppressed the nausea symptoms in the patients.[5],[6]

The incidence of vomiting between both groups showed no significant result (P < 0.05). Dexamethasone is a prostaglandin antagonist, giving effect as an antiemetic by releasing endorphin which results in improved mood and higher appetite.[4] Dexamethasone is belonged to glucocorticoid group, blocking the serotonin receptor (5-HT) at cortex cerebral, causing emesis and cortisol production stimulation. It also decreases vagal and splanchnic nerve damage resulting in better recovery.[10]

Insignificant result of vomiting incidence between two groups could also be caused by gender, age, history of smoking, history of motion sickness, history of previous PONV. PONV were more commonly experienced by women. Type of surgery could play as one factor influencing the result, where laparoscopy gynecology and cholecystectomy have higher risk of nausea and vomiting due to autonomic nerve stimulation inside the abdomen. Other factors were duration of anesthesia, anesthetic agent, length of surgery, and opioid administration.[10],[11] The results were similar to Manoharan A et al, which elaborated about risk factors of PONV.[12]

The incidence increased at 12-hours and 24-hours postoperative. Based on the pharmacokinetic profile, haloperidol has longer duration of action (24-hours)[5] compared to dexamethasone (12 hours), which may be the reason why the incidence of vomiting at 12 hours and 24 hours postoperative increased. A research conducted by Ho et al.[13] showed that dexamethasone was effective in reducing the incidence of early and late onset nausea and vomiting until 12 hours postoperative. Smith et al.[5] showed that haloperidol could reduce PONV until 24 hours postoperative. If the patients experienced nausea and vomiting, 4 mg intravenous ondansetron was administered as the rescue antiemetic, especially at 12 hours and 24 hours postoperative. In this research, there were 9 cases where ondansetron was administered, 3 patients from haloperidol group and 6 patients from dexamethasone group.[5],[13]

The effectiveness of haloperidol compared to dexamethasone as analgesic or pain control after laparoscopic surgery has not been studied widely. Chu et al.[14] reported no difference on the intensity of postoperative pain between both groups. The mean values of the pain score evaluated using VAS in both groups were 2 to 4 during 2–24 hours postoperative observation period. Sharma et al.[15] reported that the need for analgesia is higher in haloperidol group, however, it was not statistically significant. The result shown were contrary to this study’s finding, where the pain score in haloperidol group was lower with significant result (P < 0.005). However, dexamethasone used as analgesic did give effect on lowering the pain rather than not giving any. One meta-analysis reported that dexamethasone had lower VAS pain scores compared to control at two hours [MD -0.49 (95% CI = -0.83 - -0.15, P = 0.005)] and 24 hours [MD -0.48 (95% CI = -0.62 - -0.35, P < 0.001)] postoperative period after laparoscopic surgery, but not in after abdominal surgery or middle ear surgery.[16]

This research still has several limitations, such as various type of surgery, either intraperitoneal and retroperitoneal, which were difficult to be separated into subgroup, which would affect the risk of nausea and vomiting, long duration of surgery, and intraoperative opioid administration. Those factors together could affect and increased the incidence of PONV. There were also several factors, such as gender, history of smoking, history of motion sickness and previous PONV, which could not be controlled and adjusted.


  Conclusion Top


One milligram intravenous haloperidol has better effect in reducing the nausea incidence and VAS pain score after laparoscopic surgery in adult patients compared to 5 mg intravenous dexamethasone, but not in vomiting. Therefore, 1 mg intravenous haloperidol can be suggested as one of the alternatives to prevent PONV in adult patients after laparoscopic surgery, especially under regional anesthesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
East JM, Mitchell DI Postoperative nausea and vomiting in laparoscopic versus open cholecystectomy at two major hospitals in Jamaica. West Indian Med J 2009;58:130-7.  Back to cited text no. 1
    
2.
Gupta S, Choudhary RK A comparative clinical study of prevention of postoperative nausea and vomiting using granisetron and ondansetron in laparoscopic surgeries. J Anesthesiol 2010;26:1.  Back to cited text no. 2
    
3.
Shinn HK, Lee MH, Moon SY, Hwang SI, Lee CS, Lim HK, et al. Post-operative nausea and vomiting after gynecologic laparoscopic surgery: Comparison between propofol and sevoflurane. Korean J Anesthesiol 2011;60:36-40.  Back to cited text no. 3
    
4.
Arslan M, Çiçek, Kalender HÜ, Yilmaz H Preventing postoperative nausea and vomiting after laparoscopic cholecystectomy: A prospective, randomized, double blind study. Curr Ther Res - Clin Exp 2011;72:1-12.  Back to cited text no. 4
    
5.
Smith JC 2nd, Wright EL Haloperidol: An alternative butyrophenone for nausea and vomiting prophylaxis in anesthesia. Aana J 2005;73:273-5.  Back to cited text no. 5
    
6.
Brettner F, Janitza S, Prüll K, Weninger E, Mansmann U, Küchenhoff H, et al. Gender-specific differences in low-dose haloperidol response for prevention of postoperative nausea and vomiting: A register-based cohort study. Plos One 2016;11:e0146746.  Back to cited text no. 6
    
7.
Pierre S, Whelan R Nausea and vomiting after surgery. Contin Educ Anaesthesia, Crit Care Pain 2013;13:28-32.  Back to cited text no. 7
    
8.
Chaparro C, Moreno D, Ramírez V, Fajardo A, González D, Sanín A, et al. Haloperidol as prophylactic treatment for postoperative nausea and vomiting: systematic literature review. Colomb J Anesthesiol 2013;41:34-43.  Back to cited text no. 8
    
9.
Büttner M, Walder B, von Elm E, Tramèr MR Is low dose haloperidol a useful antiemetic? Am Soc Anesthesiol 2004;101:1454-63.  Back to cited text no. 9
    
10.
Chu CC, Hsing CH, Shieh JP, Chien CC, Ho CM, Wang JJ The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting. Eur J Pharmacol 2014;722:48-54.  Back to cited text no. 10
    
11.
Yi MS, Kang H, Kim MK, Choi G, Park Y, Baek CW, et al. Relationship between the incidence and risk factors of postoperative nausea and vomiting in patients with intravenous patient-controlled analgesia. Asian J Surg 2017;41:301-6.  Back to cited text no. 11
    
12.
Manoharan AK, Mallick NA, Thangavelu S A cross sectional study on postoperative nausea and vomiting – risk prediction and assessment in patients undergoing elective surgical patients. Int J Contemp Med Res 2017;4:640-4.  Back to cited text no. 12
    
13.
Ho CM, Wu HL, Ho ST, Wang JJ Dexamethasone prevents postoperative nausea and vomiting: Benefit versus risk. Acta Anaesthesiol Taiwan 2011;49:100-4.  Back to cited text no. 13
    
14.
Chu CC, Shieh JP, Tzeng JI, Chen JY, Lee Y, Ho ST, et al. The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy. Anesth Analg 2008;106:1402-6, table of contents.  Back to cited text no. 14
    
15.
Sharma S, Gnanasekar N, Kurhekar P Comparison of dexamethasone, granisentron and haloperidol in prevention of postoperative nausea and vomiting following laparoscopic surgeris: A prospective, double-blinded study. Glob J Anesth 2019;6:002-5.  Back to cited text no. 15
    
16.
Waldron NH, Jones CA, Gan TJ, Allen TK, Habib AS Impact of perioperative dexamethasone on postoperative analgesia and side-effects: Systematic review and meta-analysis. Br J Anaesth 2013;110:191-200.  Back to cited text no. 16
    


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    Tables

  [Table 1], [Table 2], [Table 3]



 

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