Postoperative nausea: inhalational agents

Postoperative nausea and vomiting (PONV) is a common complication of general anesthesia, affecting roughly 20-30% of all patients, but up to 80% of high risk patients [1,2,3]. It is also a major cause of patient dissatisfaction. In one study, more patients rated vomiting as their most undesirable anesthetic outcome (24%) over gagging on the endotracheal tube (22%), pain (21%), or recall without pain (20%) [4].

Volatile agents are a well-known cause of PONV and are the leading risk factor for vomiting in the early postoperative period (0-2 hours). After this period, other risk factors, such as childhood, early PONV, and use of postoperative opioids become the main predictors [5]. Modern volatile anesthetics do not appear to differ significantly in their emetogenic potency, despite major differences in their pharmacokinetic properties. Multiple studies have shown similar incidences of PONV with isoflurane, enflurane, sevoflurane, and desflurane, and an increased incidence of PONV with volatile agents when compared to total intravenous anesthesia (TIVA) with propofol (19% reduction in early PONV), or regional techniques alone (patients receiving general anesthesia have been shown to be up to 11 times more likely to experience PONV) [3,6,7,8]. There appears to be a dose-dependent relationship between volatile agents and PONV, with longer duration of use being associated with increased incidence of PONV (however, duration of surgery itself – regardless of anesthetic technique used – is an independent risk factor for PONV) [9].

It is poorly understood how volatile agents contribute to PONV [3]. Isoflurane and halothane have been shown to enhance 5-HT₃ receptor function in cell-based assays, which could contribute to stimulation of vagal afferent pathways implicated in nausea and vomiting [10]. Other studies have shown that in animal models, inhalational agents directly stimulate vagal afferents [11]. One study showed that patients experienced more dizziness after sevoflurane than propofol, perhaps suggesting an effect on the vestibular system [12]. It is also known that volatile agents disrupt normal gastrointestinal function, with gastric dysrhythmias being an established biomarker for nausea and vomiting [13]. However, the exact mechanisms through which volatile agents cause PONV have yet to be elucidated [3].

Nitrous oxide (N₂O) is also a contributor to PONV, although early studies likely overemphasized its effect. Subsequent studies have shown that the emetogenic effects of N₂O are less than that of volatile anesthetics; however, its emetogenic properties are additive, meaning that adding N₂O to a volatile anesthetic further increases the chances of PONV [6]. Furthermore, this risk likely increases with an increased inspiratory concentration of N₂O, as well as increased duration of N₂O exposure [14,15]. However, a more recent study showed that there was no difference in the incidence of PONV when 70% N₂O was added during the last 30 minutes of an isoflurane-based anesthetic for laparoscopic vaginal hysterectomy (the rescue antiemetic was actually required less frequently in the N₂O group, and there was reduced time to extubation, eye opening, and orientation) [16]. Other studies have shown that any increased risk of PONV with N₂O is eliminated by pretreatment with one or more common antiemetics, such as dexamethasone or ondansetron [17]. Thus, although there is broad agreement that N₂O contributes to PONV, there remains some controversy as to the extent of its effect.

As with the volatile agents, the mechanism of N₂O-associated PONV is poorly understood, but it has been hypothesized to occur though changes in middle ear pressure, bowel distension, activation of the dopaminergic system in the chemoreceptor trigger zone, as well as interaction with opioid receptors [16].

In sum, inhalational agents remain an important contributor to PONV, particularly in the early postoperative period. Alternative techniques, such as TIVA and regional anesthesia, as well as multi-agent antiemetic prophylaxis, should be considered in high-risk patients.