LETTERS TO EDITOR Year : 2021  |  Volume : 65  |  Issue : 6  |  Page : 487-488  

Intravenous amisulpride: A safer and possibly effective anti-emetic for postoperative nausea and vomiting

Abhijit Nair1, Suresh Seelam2
1 Department of Anaesthesiology, Ibra Hospital, Ministry of Health-Oman, Sultanate of Oman
2 Department of Anaesthesiology, Royal Hospital, Muscat, Ministry of Health-Oman, Sultanate of Oman

Date of Submission14-Feb-2021Date of Decision18-Mar-2021Date of Acceptance18-Mar-2021Date of Web Publication22-Jun-2021

Correspondence Address:
Abhijit Nair
Department of Anaesthesiology, Ibra Hospital, Ministry of Health-Oman, P.O. Box 275, Ibra-414
Sultanate of Oman

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ija.IJA_102_21

How to cite this article:
Nair A, Seelam S. Intravenous amisulpride: A safer and possibly effective anti-emetic for postoperative nausea and vomiting. Indian J Anaesth 2021;65:487-8
How to cite this URL:
Nair A, Seelam S. Intravenous amisulpride: A safer and possibly effective anti-emetic for postoperative nausea and vomiting. Indian J Anaesth [serial online] 2021 [cited 2021 Jun 22];65:487-8. Available from: https://www.ijaweb.org/text.asp?2021/65/6/487/319091

Sir,

Postoperative nausea and vomiting (PONV) is a common phenomenon after receiving an anaesthetic for surgery. Currently, the prevalence of PONV has been estimated to be 30-40% even after two or three prophylactic antiemetic medications and in patients with all four of the Apfel risk factors for PONV.[1] The most common factors predisposing to PONV are the female gender, history of PONV and/or motion sickness, non-smokers, younger age group patients, volatile anaesthetic with or without nitrous oxide, opioids use. PONV not only adds significant postoperative discomfort and dissatisfaction but also increases the length of hospital stay and overall cost of treatment. Presently the commonly used medications for PONV prophylaxis are dexamethasone, 5 HT3-antagonists (ondansetron, ramosetron, palanosetron), anti-histaminic, neurokinin-1 receptor antagonist aprepitant, scopolamine, and metoclopramide.[2],[3]

Amisulpride is a potent and selective dopaminergic D2 and D3 receptor antagonist which was available for clinical use as an atypical antipsychotic since 1970. It became popular due to the lesser incidence of extrapyramidal effects with recommended doses (50-1200 mg) at that time. Recently the United States Food and Drug Administration (US-FDA) has approved intravenous (IV) amisulpride for managing PONV. The D2 receptor is notorious for manifesting PONV even in surgical patients. Therefore, it was hypothesised that drugs with D2 receptor antagonist properties can be used as prophylaxis and for treating PONV. Droperidol was developed with this knowledge and was used successfully till it was issued a black-box warning in 2001 due to reports of prolonged QTc and life-threatening arrhythmias like torsade de pointes.[4]

QTc prolongation mediated by dopaminergic antagonists is because of binding to the potassium ion channel human ether-à-go-go-related gene (hERG). Antiemetics like droperidol, haloperidol, and prochlorperazine have a high affinity to hERG channel and thus the higher propensity of developing arrhythmias. Amisulpride has an edge over other agents in this regard because its affinity to hERG channel is less than 100 times weaker. The effect of IV amisulpride on QTc was demonstrated in a study by Täubel et al.[5] Authors compared a 5 mg single dose with a 40 mg IV amisulpride in 40 healthy subjects. They concluded that there is dose-dependent QTc prolongation (with 40 mg dose). However, the recommended dose is 5-10 mg IV which is considered safe. The use of IV amisulpride has not demonstrated any serious drug interactions yet and is devoid of enzyme induction or inhibition of cytochrome liver enzymes. All antipsychotics including amisulpride have a propensity of QTc prolongation therefore caution should be exercised.

The initial IV preparation of amisulpride was known by the name APD421. As early as 2013, Kranke et al. conducted a randomised, double-blind, placebo-controlled, multicentric trial by recruiting 215 adult surgical patients with more than 2 Apfel risk factors for PONV undergoing surgery and expected to last more than 1 hour with standardised inhalational anaesthesia.[6] The authors concluded that when administered before surgery, amisulpride i.e., APD421 is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. Several studies followed thereafter and established the safety and efficacy of IV amisulpride [Table 1]. It has been shown in pharmacokinetic studies that after the initial IV dose of 5-10 mg, there are therapeutic levels for at least 24 hours with a terminal half-life of 4-6 hours and a complete clearance from the system in approximately 96 hours.

Table 1: Published Papers Which Investigated Efficacy and Safety of Intravenous Amisulpride

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Amisulpride is presently marketed as BARHEMSYS by Acacia Pharma, United States. US-FDA has approved its use for preventing PONV, either alone or in combination with another antiemetic and also for treating PONV in patients who have received antiemetic prophylaxis with an agent of a different class or those who have not received prophylaxis.It should be used with caution in patients with rhythm disturbances, electrolyte abnormalities (low potassium/magnesium levels), and with other drugs causing QTc prolongation. Future studies could focus on the efficacy of amisulpride in patients undergoing specific surgeries with a high propensity for PONV.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 

   References 
1.Gan TJ, Kranke P, Minkowitz HS, Bergese SD, Motsch J, Eberhart L, et al. Intravenous amisulpride for the prevention of postoperative nausea and vomiting: Two concurrent, randomized, double-blind, placebo-controlled trials. Anesthesiology 2017;126:268-75.  
    2.Li J, Ye H, Shen W, Chen Q, Lin Y, Gan X. Retrospective analysis of risk factors of postoperative nausea and vomiting in patients undergoing ambulatory strabismus surgery via general anaesthesia. Indian J Anaesth 2020;64:375-82.  
  [Full text]  3.Kumar A, Solanki SL, Gangakhedkar GR, Shylasree TS, Sharma KS. Comparison of palonosetron and dexamethasone with ondansetron and dexamethasone for postoperative nausea and vomiting in postchemotherapy ovarian cancer surgeries requiring opioid-based patient-controlled analgesia: A randomised, double-blind, active controlled study. Indian J Anaesth 2018;62:773-9.  
[PUBMED]  [Full text]  4.Habib AS, Kranke P, Bergese SD, Chung F, Ayad S, Siddiqui N, et al. Amisulpride for the rescue treatment of postoperative nausea or vomiting in patients failing prophylaxis: A randomized, placebo-controlled phase III trial. Anesthesiology 2019;130:203-12.  
    5.Täubel J, Ferber G, Fox G, Fernandes S, Lorch U, Camm AJ. Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects. Br J Clin Pharmacol 2017;83:339-48.  
    6.Kranke P, Eberhart L, Motsch J, Chassard D, Wallenborn J, Diemunsch P, et al. I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: A randomized, double-blind, placebo-controlled, multicentre trial. Br J Anaesth 2013;111:938-45. https://www.accessdata. fda.gov/drugsatfda_docs/label/2020/209510s000lbl.pdf. [Last accessed on 2021 Feb 02].  
    

 
 

  [Table 1]