Simulated plasma concentrations of propofol during the first 6 h postoperatively. Propofol administered as an induction agent (PI); propofol administered for induction and at the end of surgery (PIP); propofol used for both induction and maintenance of anesthesia (PP). The bold lines indicate median concentrations for each group.
Propofol versus thiopental in middle ear surgery
In a double-blind, randomized trial, Honkavaara et al. compared the antiemetic efficacy of thiopental (1.0 mg/kg) versus propofol (0.5 mg/kg) administered at the end of middle ear surgery, a procedure often associated with emetic sequelae[11]. The subhypnotic dose of propofol provided superior prophylaxis against retching and vomiting during the first 6 postoperative hours. The authors noted, however, that the incidence of nausea was not significantly reduced by propofol when compared with thiopental.
Propofol versus inhaled anesthetics
In a systematic review of the literature, Gupta et al. compared postanesthesia recovery from either propofol, isoflurane, desflurane or sevoflurane[12]. The authors reported that a propofol infusion was associated with a lower incidence of PONV and postdischarge nausea and vomiting (PDNV) over inhaled anesthetics, with a number needed-to-treat (NNT) of 8.6 and 11.2 and an NNT of 12.5 and 10.3 for PONV and PDNV, respectively.
Visser et al. conducted a randomized trial involving over 2,000 surgical patients randomized to receive anesthesia with either isoflurane–nitrous oxide or TIVA with propofol. TIVA with propofol resulted in a statistically significant reduction of PONV compared with isoflurane–nitrous oxide anesthesia, with an NNT of 6[13].
As experience with the administration of TIVA has grown and costs have declined, the use of TIVA with propofol has become increasingly popular, particulary for use in outpatient procedures. However, recent financial analyses suggest that the routine use of TIVA for prophylaxis against PONV is not cost-effective[13]. Therefore, it would be reasonable to reserve the use of propofol TIVA for patients who are at the highest risk for experiencing PONV. Gan recommends considering TIVA with propofol in patients with at least four of the following PONV risk factors: female gender, nonsmoker status, history of PONV or motion sickness, or use of postoperative opioid medications[14]. Additionally, patients undergoing laparoscopy, laparotomy, major breast surgery, otolaryngologic surgery, craniotomy, plastic surgery or strabismus surgery are at increased risk for PONV[14].
Patient-controlled propofol for PONV
Gan et al. evaluated the efficacy of patient-controlled (on-demand) subhypnotic doses of propofol for the direct treatment of PONV[15]. Patients undergoing ambulatory surgery who experienced significant nausea (defined as a nausea score of at least 5 on an 11-point nausea verbal rating scale) or emesis and who requested an antiemetic within 1 h of entry to the PACU were randomized to receive either propofol 20 or 40 mg, or intralipid as a placebo. The authors found that patients receiving 20 mg of propofol experienced a 25% lower incidence of nausea, and patients receiving 40 mg of propofol experienced a 29% lower incidence of nausea compared with the placebo group (20 mg dose versus placebo, P = 0.03; 40 mg dose versus placebo, P = 0.006). Additionally, the time to discharge from the PACU was significantly shorter in the groups receiving propofol compared with the placebo group (20 mg propofol, 131 ± 35 [mean ± standard deviation] min; 40 mg propofol, 141 ± 34 min; placebo, 191 ± 92 min; P = 0.005). Because the authors found no difference in efficacy between the two doses of propofol, they recommended the lower 20-mg demand dose of propofol in order to avoid the side effects that are possible with a higher dose.
Benzodiazepines
Benzodiazepines, such as midazolam and lorazepam, have sedative, anxiolytic and amnestic properties as a result of their ability to enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA). Benzodiazepines have been demonstrated, in both pediatric and adult populations, to decrease the anxiety often associated with anesthesia and surgery, thereby decreasing the incidence of PONV[16].
Midazolam versus placebo in children undergoing tonsillectomy
In a double-blind study, Splinter et al. assessed the antiemetic effect of midazolam in pediatric patients undergoing tonsillectomy[17]. The children (n = 215) were administered either placebo or midazolam 75 μg/kg IV after induction of anesthesia with nitrous oxide and halothane. The administration of midazolam was associated with a lower incidence of vomiting when compared with placebo (42% versus 57%, respectively; P < 0.02). Additionally, the placebo group experienced a higher incidence of unscheduled admissions to the hospital secondary to nausea and vomiting (9% versus 2%, respectively; P < 0.05). It was concluded that IV midazolam administered intraoperatively reduces vomiting after tonsillectomy in children.
Midazolam versus propofol during cesarean section
Tarhan et al. compared the effects of subhypnotic doses of midazolam and propofol on peripartum nausea and vomiting during cesarean deliveries under spinal anesthesia[18]. Parturients received, at random, either IV placebo (normal saline), a propofol infusion (1.0 mg/kg/h), or a midazolam infusion (1.0 mg/h) once the umbilical cord was clamped. The researchers found that the incidence of nausea and vomiting was significantly lower in patients who received propofol or midazolam compared with those in the control group, leading to the conclusion that midazolam is as effective as propofol in reducing the incidence of nausea and vomiting in women undergoing cesarean section.
Midazolam versus metoclopramide during cesarean section
Shahriari et al. compared the prophylactic antiemetic efficacy of a bolus dose of midazolam versus metoclopramide during cesarean delivery under spinal anesthesia[19]. In this study, 80 parturients were randomly allocated to receive midazolam (2 mg) or metoclopramide (10 mg) immediately preceding skin incision. The incidence of nausea and vomiting was lower in the midazolam group compared with those receiving metoclopramide (15% versus 52%, respectively). However, sedation scores within the first three postoperative hours were significantly higher in patients receiving midazolam. Additionally, there were incidences of respiratory depression (respiratory rate <10 breaths per minute) observed in 17 patients who had received midazolam; no respiratory depression was observed in those receiving metoclopramide. Given these findings, the authors emphasized the need for additional studies to further evaluate the safety of midazolam in cesarean deliveries.
Midazolam versus ondansetron in adults
Lee et al. compared the efficacy of midazolam with ondansetron in preventing PONV in 90 patients scheduled for either hysteroscopy or ureteroscopy[20]. IV midazolam (2 mg) or ondansetron (4 mg) was administered 30 min prior to the conclusion of the procedure. The percentages of patients who experienced PONV during the first 24 h postoperatively were not significantly different between the midazolam and ondansetron groups (30% and 27%, respectively), suggesting antiemetic prophylaxis with ondansetron was not superior to midazolam in these procedures.
Lorazepam versus droperidol in children
In a double-blind study, Khalil et al. compared the efficacy of lorazepam versus droperidol in reducing emetic symptoms of children (1–13 years of age) undergoing strabismus correction surgery[21]. The children were randomly allocated to receive IV droperidol (75 μg/kg), IV lorazepam (10 μg/kg) or placebo. They reported that lorazepam and droperidol resulted in a lower incidence of postoperative vomiting (POV) compared with placebo (P < 0.024), with no difference between lorazepam and droperidol.
Alpha-2 adrenergic agonists (clonidine and dexmedetomidine)
Clonidine, a centrally acting agonist of alpha-2 adrenergic receptors, is commonly used to reduce blood pressure by decreasing peripheral vascular resistance. Clonidine binding to its receptors inhibits the release of norepinephrine, which decreases sympathetic tone[22]. Although clonidine has been historically prescribed for its antihypertensive properties, other uses have been described more recently. New studies have demonstrated the efficacy of clonidine in treating postoperative, neuropathic and cancer-associated pain[23].
Clonidine is also effective as a preanesthetic medication in the adult and pediatric populations. Clonidine has been shown to blunt the sympathetic response to anesthesia, decrease intraoperative anesthetic requirements, provide preoperative sedation, stabilize perioperative hemodynamics, and even prevent POV[24].
Some clinical trials in adults have suggested that oral clonidine is effective in reducing the incidence of PONV. However, there are conflicting results in the literature regarding clonidine’s antiemetic efficacy[25–27].
Clonidine versus placebo in adults undergoing ear surgery
Taheri et al. evaluated the effect of oral clonidine on PONV in adult patients undergoing outpatient ear surgery[25]. In a double-blind study, 60 adults were randomized to receive either clonidine or placebo. A complete response (no PONV and no need for rescue antiemetic medication) during the first 24 h postoperatively was 33% with placebo and 67% with clonidine (P = 0.01). The authors concluded that oral premedication with clonidine reduces the incidence of PONV in adults undergoing outpatient ear surgery.
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