G. Preventive strategies and pharmacotherapy
Prevention of PONV is paramount in the management of PONV and the benefit of pharmacological prophylaxis in moderate and high-risk patients is without dispute. However, the benefit is less clear in low-risk patients. Authorities like the Society for Ambulatory Anesthesia (USA) and the Royal College of Anaesthetists (UK) recommend against the routine use of anti-emetic medication in low-risk patients in ambulatory settings. Therefore, prophylaxis must be selected by weighing the risks and benefits of each drug in any given scenario.
Prevention of PONV starts with the identification of moderate and high-risk patients utilizing various scoring systems (Apfel) that identify patient and surgical characteristics to define risk (Table 7.3). Once identified, the provider can then take measures to decrease the risk of PONV in patients at risk. These measures may include pharmacologic prophylaxis with dexamethasone and/or5-HT3 antagonist, scopolamine transdermal patch, avoidance/minimization of conventional pharmacological triggers (e.g., inhalational agents, opioids, nitrous oxide, neostigmine), maximization of regional anesthetic techniques, and utilization of non-pharmacological strategies when possible. The intraoperative administration of ultrashort-acting remifentanil may not be as problematic as other opioids in causing PONV. However, it must be remembered that remifentanil can cause hyperalgesia and an increased need for analgesic agents postoperatively. Utilization of a total intravenous anesthetic (TIVA) technique with aggressive pharmacologic prophylaxis has also been demonstrated to eliminate vomiting and significantly decrease nausea in a group of high-risk patients.
History of PONV or motion sickness
Age: younger patients have more PONV
Volatile anesthetic agents use
Nitrous oxide use
Duration of surgery
Type of surgery
High-risk procedures include ENT surgery, gynecologic surgery, strabismus surgery, breast surgery, shoulder surgery
For treatment of a failed prophylactic anti-emetic for PONV occurring in the PACU, an anti-emetic from a different drug class not previously given should be administered. Additionally, evidence proves that combination therapy is more efficacious than single agent therapy.[37,38,40] For example, if the patient received ondansetron prior to emergence, another dose of ondansetron is unlikely to be effective. Instead, an anti-histamine or phenothizine would be a better option. Due to the relatively short half-life of most anti-emetic medications, however, prophylactic anti-emetics from the same drug class may need to be repeated after 12–24 hours.
If no prior anti-emetic prophylaxis was given, a 5-HT3 antagonist should be the initial treatment. Second-line treatment of breakthrough PONV should utilize droperidol, promethazine, small doses of propofol, dimenhydrinate, or dexamethasone.[37,41–43] All anti-emetic therapies and their dosing are found in Table 7.4.
It must be noted, however, that in 2001, the FDA placed a “black-box warning” on droperidol after the discovery that some patients had experienced episodes of ventricular dysrhythmias after receiving droperidol – some of which were fatal. Although the dosages these patients received were far greater than commonly used anti-emetic dosages, this has significantly reduced the popularity of droperidol as an anti-emetic. The authors agree with many experts that this “black-box warning” should not preclude the use of droperidol for PONV in anti-emetic dosages (0.5–0.75 mg). We do, however, typically administer it at the beginning of the case because by doing so, we have monitored the patient for the requisite “2–3 hours” recommended by the FDA prior to discharge.
In patients with known congenital or acquired prolonged QT syndrome and in pediatric patients who may have undiagnosed long QT syndrome, one should be especially cautious with the use of any anti-emetic that may prolong the QT interval (droperidol, 5-HT3 antagonists, phenothiazines). At the authors’ institution, the electrophysiologists prefer the use of scopolamine, dexamethasone, and anti-histamines such as dimenhydrinate in patients with known QT prolongation. If PONV persists despite these therapies, they recommend the use of other anti-emetics (e.g., ondansetron) only with inpatient ECG monitoring.
The treatment of recognized PONV should also include the treatment of conditions which may exacerbate PONV, such as anxiety, pain, hypotension, hypoxia, and inadequate hydration. Commonly used drugs for the prevention and treatment of PONV are listed in Table 7.4. These drugs are also discussed below along with their mechanisms of action, common adverse effects, and cautions prior to use.
Act through antagonism of 5-HT3 receptors.
Adverse effects: dose-dependent QT interval prolongation, headache, dizziness.
Caution: avoid in patients with congenital or prolonged QT.
Act through antagonism of dopaminergic (D2) receptors in the central nervous system.
Adverse effects include sedation and extrapyramidal side effects such as dystonia and akathisia.
Caution: avoid in patients with Parkinson’s disease.
Act through antagonism of central D2 receptors, mild alpha receptor antagonism.
Adverse effects include sedation, QT interval prolongation, hypotension, rare extrapyramidal side effects, neurolepsis.
Act through antagonism of dopamine (D2) receptor antagonism, some 5-HT3 receptor antagonism.
Adverse effects include extrapyramidal side effects, agitation, sedation.
Act through H1-receptor antagonism, some antidopaminergic (promethazine) antimuscarinic (diphenhydramine) and anti-alpha adrenergic effects and antiserotonergic effects (promethazine).
Adverse effects include sedation, anticholinergic side effects, QT interval prolongation in overdose.
Caution: sedative action.
Act through antagonism of CNS muscarinic receptors.
Adverse effects include antimuscarinic side effects such as dry mouth, sedation, blurred vision, tachycardia, inhibition of sweating, urinary retention, etc., agitation in elderly patients.
Exact mechanism of action still unknown.
Adverse effects include hyperglycemia in susceptible population, potential for immune suppression, delayed wound healing, etc.
Acts through antagonism of NK 1 receptor in the central and peripheral nervous system and inhibition of action of substance P47.
Acts on cannabinoid receptors (CB1 and CB2 receptors) in the peripheral nervous system, CNS and immune cells.
Can cause drowsiness, confusion, administration can precipitate psychosis and panic attacks.
Efficacy is not documented for PONV.
Precise mechanism of action of ephedrine is unknown, although several studies have confirmed positive effect on PONV. Midazolam most likely works by decreasing dopamine’s input at the chemoreceptor trigger zone; it is effective when given after induction, rather than as a premedication.
Adequate hydration with fluids helps to prevent PONV as the NPO patient may be dehydrated which may be exacerbated by intraoperative fluid losses. In addition, acupuncture and acupressure have been shown to decrease the incidence of PONV by both a direct and opioid-sparing effect. Acustimulation at the P6 acupoint also has demonstrated efficacy in the prevention of PONV. Uncontrolled pain may contribute to PONV, although this may be a result of increased perioperative opioid administration. Perioperative anxiolysis and hypnosis may also have a beneficial effect on prevention of the PONV.
Approximately 30–60% patients may experience PONV after discharge to home and this is commonly termed post-discharge nausea and vomiting (PDNV), which may lead to readmission or emergency department visit.[49,50] PDNV may persist many days beyond surgery. Commonly recognized risk factors for PDNV include: (i) female gender; (ii) age < 50 years; (iii) history of PONV; (iv) PACU opioids; and (v) nausea in the PACU. Possible useful approaches to help decrease the incidence of PDNV include: (i) prophylactic combination anti-emetic therapy; (ii) TIVA substituting propofol for inhalation anesthesia; (iii) P6 acupoint stimulation; and (iv) use of home anti-emetics. The management of PDNV should extend into the postoperative and post-discharge period and include prescription of oral anti-emetics such as ondansetron or dolasetron, more expensive options such as aprepitant and additional non-opioid-based analgesics (NSAIDs, acetaminophen). Continuous pump infusions of local anesthetics for nerve catheters should be utilized for opioid-sensitive patients.[51,52]
The authors’ preference for prevention and management of PONV in a high-risk patient receiving GA: