(previous POV, motion sickness or family history of POV)
(tonsillectomy, tympanoplasty
strabismus)
strabismus)
NA, not applicable; PONV, postoperative nausea and vomiting; POV, postoperative vomiting; VPOP, vomiting in the postoperative period.
b Low risk: total score of 0–1; moderate risk: total score of 2–3; high risk: total score of 4–6.
c The factors of predisposition to POV, duration of anesthesia >45 mins, high-risk surgery and multiple doses of opioids are scored as 0 or 1 only. Age is scored as 0, 1 or 2 according to criteria listed above.
Factors that have been disproved or of limited clinical relevance in adults have been discussed in other chapters. In children, preoperative anxiety was not found to be associated with increased POV[13], and routine gastric suctioning and intraoperative therapeutic suggestion did not reduce POV[5,13–15]. Whilst airway and pulmonary complications are higher in children coming from households with smokers, the effect of second-hand smoking on POV in children is unknown[2,5,16,17]. The preoperative visit may be an opportunity to introduce the child’s caretakers to smoking cessation programs.
Reducing baseline risks of POV
Strategies recommended to reduce baseline risk and incidence of POV include[2,5]:
the avoidance of general anesthesia by the use of regional anesthesia
preferential use of propofol infusions
avoidance of nitrous oxide
avoidance of volatile anesthetics
minimization of perioperative opioids
adequate hydration.
Regional anesthesia is associated with less PONV than general anesthesia in both children and adults[2]. In the pediatric patient population, regional anesthesia is usually performed after induction of general anesthesia to reduce stress associated with inserting needles. A major benefit of a combined general and regional anesthetic technique is the reduction in perioperative opioid requirements, and consequently, reduced postoperative emesis. Children randomized to a wrist block during hand surgery had less emesis than those receiving perioperative opioids[18]. Similarly, children receiving a peribulbar block, subtenon block or topical lidocaine during strabismus repair had less emesis than a control group[19,20].
When general anesthesia is required, use of propofol for induction and maintenance of anesthesia lowers the incidence of early PONV occurring within the first 6 h[21]. Children receiving intraoperative propofol in subhypnotic doses (bolus of 1 mg/kg followed by an infusion at 20 μg/kg/min), combined with dexamethasone or tropisetron during tonsillectomy procedures, had less emesis than those receiving dexamethasone or tropisetron alone[22,23]. However, single induction doses of propofol have no effect on POV[2].
The combination of propofol and air/oxygen (total intravenous anesthesia) has additive effects, reducing PONV risk by approximately 25% in adults[24,25]. Nitrous oxide has little impact when the baseline risk for PONV is low, but avoidance of nitrous oxide is associated with decreased POV in high-risk subjects[5,26].
Baseline risk for PONV can also be reduced by minimizing perioperative opioids by supplemental nonopioid analgesics or regional nerve blocks. Perioperative nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, alpha-2 agonists, such as clonidine and dexmedetomidine, and ketamine may have a morphine-sparing effect with decreased opioid-related PONV[27–32]. A systematic review of 12 trials with 928 children showed less emesis in a group receiving NSAIDs (odds ratio, 0.49; 95% confidence interval (CI), 0.29–0.83)[28].
Adequate hydration is another simple strategy to reduce emesis. High-dose intravenous fluids at 30 mL/kg are associated with less emesis than the standard 10 mL/kg therapy in children[33,34]. However, routine gastric decompression and limiting oral intake after surgery are ineffective in reducing pediatric POV[35,36]. Other strategies initially thought to be effective were later shown to have minimal or no effect, including supplemental oxygen and minimization of neostigmine[2].
Prophylactic antiemetic therapy in children at increased risk for POV
In children, the POV rate can be twice as high as in adults, which suggests a greater need for POV prophylaxis in this population. Many drugs are effective for POV prophylaxis in children including 5-HT3 antagonists, steroids, antihistamines, anticholinergic drugs and dopamine antagonists, such as butyrophenones, phenothiazines and benzamides (Table 12.2).
| Drug | Dose | Maximum |
|---|---|---|
| Dexamethasone | 150 μg/kg | 5 mg |
| Dimenhydrinate | 0.5 mg/kg | 25 mg |
| Droperidola | 10–15 μg/kg | 1.25 mg |
| 5-HT3 antagonists: Ondansetron Tropisetron Granisetron Dolasetron | 50–100 μg/kg 0.1 mg/kg 40 μg/kg 350 μg/kg | 4 mg 2 mg 0.6 mg 12.5 mg |
a FDA black box warning calls for 12-lead electrocardiogram to rule out prolonged QT syndrome before administering droperidol and continuous electrocardiogram monitoring for at least 2–3 h after administering droperidol.
Ondansetron and other 5-HT3 antagonists
There is good evidence from meta-analyses and large studies to suggest that 5-HT3 antagonists and dexamethasone are the most effective antiemetics in the prophylaxis of pediatric POV[37–39]. Ondansetron was more effective than metoclopramide in 557 children undergoing adenotonsillectomy[37]. In a systematic review of children undergoing this procedure, the 5-HT3 antagonists and dexamethasone were found to be the most effective prophylactic antiemetics, with insufficient evidence for the efficacy of dimenhydrinate, droperidol or perphenazine in children[38]. Perphenazine was effective compared to placebo in children, but a 5-HT3 antagonist (ondansetron or granisetron) was more effective[40]. In a Bayesian meta-analysis of six single-drug therapies and five combinations of antiemetics in children, Engelman et al. noted that the most pessimistic expectations of single-drug prophylaxis with the 5-HT3 receptor antagonists or dexamethasone would result in a 50–60% relative risk (RR) reduction, and that the expected RR reduction of the combination is 80%[39]. In this study, the risk reduction with droperidol was 40%.
Ondansetron is effective in children as young as 1 month[41] and the pharmacokinetics have been established in children between 1 and 48 months[42]. Clearance decreased by 31%, 53% and 76% for the typical 6-, 3- and 1-month-old, respectively, compared to published data in older children aged 3–12 years, and was attributed to immaturity of cytochrome P450 enzymes. Ondansetron 0.1 mg/kg in children <6 months produced exposure similar to a 0.15 mg/kg dose in older children, suggesting a need for close monitoring when used in children <4 months old[42].
There is greater experience with ondansetron, the first available antiserotonin drug compared to other 5-HT3 antagonists, such as granisetron, dolasetron or tropisetron, but little evidence to suggest improved efficacy with any one of these drugs. Dolasetron is no longer available in the USA because of risks of cardiac arrhythmias. Tropisetron is not available in the USA but has been used in Europe. There are also no published pediatric data to make recommendations on the use of palonosetron in pediatric POV. A randomized controlled trial without a placebo arm showed no differences in the 48-h rates of POV in children receiving 0.5, 1.0 or 1.5 mg/kg palonosetron[43]. The low cost of generic ondansetron and similar efficacy makes it difficult to show any advantage in using the other first-generation antiserotonin drugs.
Data to base a recommendation on the timing of administration of these drugs in children are sparse. No differences were found in POV in children who received tropisetron immediately after induction or at the end of surgery during short tonsillectomy procedures[44].
Dexamethasone
Corticosteroids have been shown to be very effective in the prevention of POV in children, with administration at induction recommended rather than toward the end of anesthesia[39]. The mechanism of action of steroids in POV prophylaxis may be related to depletion of the serotonin precursor tryptophan, prevention of release of gut serotonin and 5-HT3 receptor sensitization to other antagonists[45]. Most studies have been with dexamethasone 0.5 mg/kg, but methylprednisolone 2.5 mg /kg is noninferior[46]. However, the dose–effect relationship of dexamethasone in POV prophylaxis is unclear. Kim et al. did not find differences in POV rates or secondary outcomes in children receiving 0.0625, 0.125, 0.25, 0.5 or 1 mg/kg (maximum dose 24 mg) during adenotonsillectomy procedures[47]. Another study of the same patient population showed a dose-dependent reduction in POV, with the best response in children receiving 0.5 mg/kg compared to 0.05 and 0.15 mg/kg doses[48]. An updated Cochrane review of steroids for tonsillectomy patients stated that “the question of appropriate dosing remains unanswered and final recommendations must await randomized dose-control trials”[49].
Older drugs
A number of older drugs are also effective in POV management. These include antihistamines (dimenhydrinate), dopamine antagonists such as butyrophenones (e.g., droperidol and haloperidol), phenothiazines (promethazine, prochlorperazine and perphenazine), benzamides (metoclopramide) and cholinergic antagonists (scopolamine). There are few dose-ranging data and limited evidence for the efficacy of these drugs. In addition, the 5-HT3 antagonists are more effective and associated with a lower side-effect profile[38,39]. Concerns about the effect of droperidol on cardiac rhythms have led to a black box warning that may not be entirely justified as similar effects on cardiac rhythm are seen with other antiemetics[50]. Side effects for metoclopramide and phenothiazines also include extrapyramidal symptoms (Table 12.3). With the availability of lower-priced generic ondansetron, the use of the older drugs is now limited to second-line options as rescue therapy when other drugs have failed or when 5-HT3 antagonists are contraindicated.
| Drug | Dose (mg/kg) | Maximum single dose (mg) | Side effects |
|---|---|---|---|
| Diphenhydramine | 1.0 | 25 | Sedation, dry mouth, blurred vision, urinary retention |
| Metoclopramide | 0.25b | 10 | Extrapyramidal reactions more common in children. Not recommended below 1 year of age |
| Phenothiazines: Perphenazine Prochlorperazinec Promethazined | 0.07 0.1–0.2 0.25–0.5 | 2.0 2.5 25 | Sedation, hypotension (particularly in hypovolemic patients), extrapyramidal syndromes can occur with phenothiazines Promethazine is contraindicated in children below 2 years. It is also an IV irritant with a risk for severe tissue injury |
| Scopolamine (IM, IV, SC)e | 0.006 | 0.3 | Drowsiness, dry mouth, visual disturbances, dizziness |
IM, intramuscular; IV, intravenous; SC, subcutaneous.
a Dose: ranging and efficacy studies are sparse for these older drugs. These drugs may be used for rescue therapy after failure of 5-HT3 antagonists and are usually not used for routine prophylaxis.
b Although higher doses may be more effective, there is a higher incidence of side effects.
c Prochlorperazine is not recommended for children under the age of 2 years or less than 10 kg body weight.
d Promethazine has two black box warnings by the FDA: (1) not to be used below 2 years because of the potential risks of fatal respiratory depression, and (2) severe tissue injury and gangrene with perivascular extravasation or unintentional intra-arterial injection. The preferred route of administration is deep IM injection and SC injection is contraindicated[51].
e Scopolamine patches should not be divided. The patch should not be used in children below 12 years of age.
Combination therapy
Prophylaxis with drugs acting at different receptor sites may be more effective even if this is an additive and not a synergistic effect[24]. Whilst low-risk patients may not require prophylactic antiemetics, those with a moderate-to-high risk of POV and children with a potential for medical sequelae from emesis (e.g., wound dehiscence, wired jaws) should receive prophylactic combination therapy with two or three antiemetics from different classes[2]. The prophylactic use of a combination of dexamethasone and ondansetron is strongly recommended in most pediatric patients at highest risk for POV unless there are contraindications (Table 12.4)[2]. This is similar to the recommendation by the Association of Paediatric Anaesthetists of Great Britain and Ireland[5].
| Drug (1) | Dose | Drug (2) | Dose | |
|---|---|---|---|---|
| Ondansetron | 0.05 mg/kg | + | Dexamethasone | 0.015 mg/kg |
| Ondansetron | 0.1 mg/kg | + | Droperidol | 0.015 mg/kg |
| Tropisetron | 0.1 mg/kg | + | Dexamethasone | 0.5 mg/kg |
Related posts:
Pharmacology of serotonin antagonists
Pharmacology of histamine, muscarine and dopamine antagonists
Pharmacology of neurokinin antagonists and novel antiemetics
Management of postoperative nausea and vomiting in inpatients and ambulatory patients
Implementing postoperative nausea and vomiting management guidelines
Nonpharmacologic management of postoperative nausea and vomiting
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
