Introduction

Postoperative nausea and vomiting (PONV) is defined as nausea and/or vomiting which occurs within 24 hours after surgery. It is the most common and undesirable side effect following surgery and affects between 20-30% of patients. However, 70-80% of high risk patients may be affected. PONV results in increased patient discomfort, costs related to delayed hospital discharge, and could also lead to serious medical complications such as pulmonary aspiration of gastric contents, or fluid and electrolyte disturbances.

Risk Factors

The aetiology of PONV is thought to be multi-factorial. They can be divided into three main groups; patient specific factors, anaesthetic agents, and the type of surgery performed.

A patient who is a female non-smoker, with a history of PONV or motion sickness, has a greater need for PONV medication. The use of intra-operative and postoperative opioids, nitrous oxide, volatile inhalational anaesthetics (ether), and some intravenous anaesthetics (ketamine, etomidate) are associated with an increase in PONV. Certain types of surgeries such as plastic (breast), gynaecological, ophthalmic (strabismus repair), ENT, laparotomy, laparoscopy and craniotomy are also known to predispose to PONV.

Pharmacological Prevention and Treatment of PONV

Prophylaxis isn’t generally indicated in low-risk patients, single drug prophylaxis is appropriate for moderate-risk patients, and multiple intervention prophylaxis is reserved for high-risk patients. Apfel et al. developed a simplified risk score consisting of four predictors for PONV.

There are four major receptor systems involved in the aetiology of PONV. Current available antiemetics may act at the cholinergic (muscarinic), dopaminergic (D2), histaminergic (H1), or serotonergic (5HT3) receptors.

Serotonin (5HT3) Receptor Antagonists

Ondansetron was the first drug of this class, and is still the most commonly used. Others include granisetron, tropisetron and dolasetron. They produce pure antagonism of the 5HT3 receptor. Gan et al. found that there was no evidence of any difference in the efficacy and safety profile of the different 5HT3 receptor antagonists in the prophylaxis of PONV. Ondansetron is well tolerated with few adverse effects; headache, light-headedness, dizziness, elevated liver enzymes, and constipation being the most commonly reported. Studies have shown that intravenous ondansetron 4-8mg given at the end of surgery is significantly better than before induction of anaesthesia in treatment of PONV.

Granisetron is more selective than ondansetron, and a low dose of 1mg given intravenously is effective in the prevention and treatment of PONV. The elimination half-life is nine hours, about two and a half times longer than ondansetron, and so may require less frequent dosing. However, its high cost limits its clinical application.

Dolasetron is a highly potent selective serotonin receptor antagonist. The recommended intravenous dose of dolasetron is 12.5mg given 15-30 minutes before the end of surgery. Dolasetron is metabolised into hydrodolasetron, which has an elimination half-life of approximately eight hours and is 100 times more potent.

Tropisetron has a longer elimination half-life of 8-12 hours compared to ondansetron. Alon et al. reported intravenous tropisetron 2mg may be effective against PONV in most surgeries. Intravenous tropisetron 5mg before the anaesthesia has been found to be effective for PONV of breast and gynaecological surgery.

Droperidol

Droperidol acts competitively on central dopaminergic receptors, and side effects include sedation, drowsiness (dose dependent), dysphoria, restlessness, and extrapyramidal reactions (rarely). Ku and Ong stated that intravenous low doses of droperidol 0.625-1.25mg have been shown to be as effective as ondansetron 4mg without increasing sedation, agitation or anxiety.

According to Kovac, numerous studies have shown that droperidol and ondansetron are similarly effective in preventing PONV in adults. However, a “black box” warning issued by the U.S Food and Drug Administration about droperidol states that it may cause death associated with prolonged QT interval and increased risk of Torsades de Pointes.

Metoclopramide

Metoclopramide is a benzamide prokinetic agent with dual sites of action, blocking the dopamine receptors in the gastrointestinal tract and centrally in the chemoreceptor trigger zone. It also antagonises serotonin receptors at high doses. Metoclopramide increases the lower oesophageal sphincter tone and facilitates gastric emptying into the small intestine. Opioid-induced PONV can be treated with metoclopramide because it reverses the gastric stasis induced by morphine. Metoclopramide is best reserved for use pre or postoperatively in those procedures where there is evidence for delayed gastric emptying, or, for patients at risk of gastro-oesphageal reflux.

Extrapyramidal side effects such as akathisia, acute dystonia, pseudoparkinsonism and tardive dyskinesia can occur. It is not recommended following gastrointestinal surgery involving anastamoses. In a meta-analysis performed by Domino et al., metoclopramide has been shown not to be as effective as ondansetron and droperidol for prophylaxis of PONV.

Phenothiazines

Promethazine and prochlorperazine exert a direct dopamine 2 receptor antagonism effect in the chemoreceptor trigger zone with moderate antihistaminergic and anticholinergic actions. Promethazine is an effective prophylactic antiemetic, although less effective than prochlorperazine, and with more sedation, more prolonged recovery period from anaesthesia, and higher incidence of extrapyramidal side effects. Both agents are believed to be effective in the treatment of opioid-induced PONV, but their use as the primary treatment of PONV is limited by their tendency to cause sedation.

Neuroleptic malignant syndrome (catatonia, cardiovascular instability, hyperthermia and myoglobinaemia mortality in excess of 10%) has been reported with prochlorperazine, promethazine, droperidol, and metoclopramide.

Other Agents

Dexamethasone, a corticosteroid administered intravenously at a dose of 8-10mg has been shown to be an effective prophylaxis for PONV. The mechanism of action is still uncertain, however its long duration of action and cost-effectiveness makes it an attractive first line treatment. Unfortunately, it has no role in the treatment of established nausea and vomiting. Early administration is required due to its slow onset of action (peak effect at 1-2 hours).

Henzi et al. reported that when there is a high risk of postoperative nausea and vomiting, a single prophylactic 8-10mg dose of intravenous dexamethasone is effective compared with placebo. Dexamethasone has been shown to be more effective when it is used in combination with other antiemetic agents (ondansetron or dolasetron) than when it is used as a single agent.

Combination Therapy

Some studies have shown repeating a second dose of a single agent is unlikely to increase efficacy. In fact, in addition to increasing the cost, it is likely to increase the risk of side effects. It is reasonable to choose additional agents with a different mechanism of actions, as a combination should be more effective than a single agent alone in inhibiting the complex emetic reflex. Combination therapy should be reserved for when a single agent is ineffective, and for those patients at high risk of PONV.

References:

  1. Alon E, Buchser E, Herrera E, Christiaens F, De Pauw C, Ritter L, et al. Tropisetron for treating established postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled study. Anesth Analg 1998; 86: 617–23.
  2. Apfel CC, Greim CA, Haubitz I, Goepfert C, Usadel J, Sefrin P, Roewer N. A risk score to predict the probability of postoperative vomiting in adults. Acta Anaesthesiol Scand 1998; 42: 495–501.
  3. Domino KB, Anderson EA, Polissar NL, Posner KL. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis. Anesth Analg 1999; 88: 1370–9.
  4. Gan T. Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs 2005; 19 (3): 225–38.
  5. Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ. Eubanks S, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003; 97; 62–71.
  6. Henzi I, Sonderegger J, Tram r MR. Efficacy, dose-response, and adverse effects of droperidol for prevention of postoperative nausea and vomiting. Can J Anaesth 2000; 47(6): 537–51.
  7. Kovac A. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000; 59(2): 213–43.
  8. Ku CM, Ong BC. Postoperative nausea and vomiting: a review of current literature. Singapore Med J 2003; 44(7): 366–74.
  9. McCracken G, Houston P, Lefebvre G. Guideline for the management of postoperative nausea and vomiting. J Obstet Gynacecol Canada 2008; 30(7): 600–7.
  10. Smith HS, Smith EJ, Smith BR. Postoperative nausea and vomiting. Ann Palliat Med 2012; 1(2): 94–102.
  11. Yuill G, Gwinnutt C. Postoperative nausea and vomiting. Update in Anaesthesia 2003; 17: 2–7.

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