Postoperative nausea and vomiting (PONV) still is the most frequent complication after strabismus surgery in children, with an incidence between 27% and 88% (1,2). In one study, PONV led to overnight admission in more than one third of ambulatory patients (3). Selective 5-hydroxytryptamine receptor antagonists are effective in prophylaxis and treatment of postoperative vomiting (4). Prior investigations focused on prophylactic and therapeutic effects of drugs, such as droperidol, metoclopramide (5,6), or scopolamine (7) on PONV, whereas the effectiveness of dimenhydrinate, a H1 receptor antagonist, is not well documented by placebo-controlled, double-blinded studies (2).
We performed a double-blinded, randomized study to investigate the effectiveness of dimenhydrinate suppositories in the prophylaxis of PONV in children undergoing strabismus surgery. Because different operative procedures in eye muscle surgery influence the incidence and severity of PONV (8), only children undergoing horizontal recess-resect (RR) procedures were included in the study. We also investigated whether oculocardiac reflex or the amount of gastric content influenced the incidence of PONV.
Our study was approved by the research ethics board of our hospital. Informed, written consent was obtained from the parents, and verbal assent was obtained from patients 7 yr of age or older. We enrolled 301 children who underwent elective RR operations with resection of at least two muscles in a prospective randomized double-blinded study. All children were aged 4 to 10 yr, ASA physical status I or II and had no history of fever, emesis, or antiemetic therapy 24 hr before surgery. Children suffering from neurologic disorders were excluded.
All children fasted at least 6 hr before surgery. Preanesthetic medication consisted of oral midazolam 0.5 mg/kg 30 min before transfer to the operating room. Efficacy of preanesthetic medication was classified as “excessive,” “good,” “fair,” or “insufficient” by the anesthesiologist. According to a randomization code generated by a person not involved in the study, each child was assigned to receive either dimenhydrinate or placebo suppositories at least 30 min before the induction of anesthesia. The anesthesiologists in charge of the patients were blinded to the randomization code and medication used. To achieve administration of the recommended dosage of 2 to 3 mg/kg, children less than 23 kg Body Weight received suppositories containing 40 mg of placebo or dimenhydrinate, while in children weighing more than 23 kg, suppositories with 70 mg of drug preparation were used.
Our standardized anesthetic regimen consisted of IV sodium thiopental (5–10 mg/kg) for induction, vecuronium bromide (0.1 mg/kg) for intubation, and halothane (1–2%) in a mixture of O2/N2O (35%/65%) for maintenance of anesthesia. No muscle relaxant reversal drugs were used.
Perioperative standard monitoring included electrocardiogram, pulse oximetry, noninvasive blood pressure, and end-tidal CO2. Before extubation, gastric suction was routinely performed. The amount of gastric content was evaluated as low (up to 10 mL), medium (10 to 50 mL), or high (more than 50 mL). At least 10 mL/kg of lactated Ringer’s solution was administered IV during anesthesia. The occurrence of oculocardiac reflex and the therapeutic administration of atropine (0.01 mg/kg IV) were recorded. Before transfer to the recovery room, all children received acetaminophen (10–20 mg/kg) per rectum for pain therapy. Rescue dimenhydrinate (40 or 70 mg) per rectum was given after two or more episodes of vomiting or on request.
Postoperative arousal was assessed on arrival at and on discharge from the recovery room by using a modification (9) of the recovery score introduced by Steward (10), which evaluates airways, consciousness, and movements on a scale from 0 to 10. The duration of surgery and the time spent in the recovery room were documented. As is our routine in our institution, all children stayed in the hospital until the next morning and were monitored for episodes of vomiting up to 18 hr after extubation. Postoperative vomiting was classified into three groups: 1) children without vomiting, 2) children with vomiting who did not need additional therapy, and 3) children with vomiting who required rescue medication.
Interval scaled data were compared by using the Mann-Whitney U-test and Student’s t-test for independent samples. The χ2 test and Fisher’s exact test were used for comparison of ordinal scaled data. Logistic regression analysis was performed to evaluate the influence of patient age, weight, sex, and number of muscles operated on. Data were presented as mean ± SD unless otherwise indicated. Based on the following assumptions, the sample size was calculated using the χ2 test before the beginning of the study: 1) the review of 200 charts of children aged 4 to 10 yr who underwent elective strabismus surgery revealed an incidence of PONV of 29% in children who underwent an RR operation, 2) a reduction of 50% in the dimenhydrinate group (from 29% to 14.5%), and 3) α = 0.05, 4) β = 0.2.
Three hundred one children participated in the study. One hundred fifty-three patients were given dimenhydrinate suppositories. One hundred forty-eight patients received the placebo preparation. There were no significant differences between study groups with respect to age, height, weight, the mean number of muscles operated on, and the duration of surgery (Table 1). In the treatment group, the oculocardiac reflex was observed in 30.7% of cases. In the placebo group, 51 children (34.5%) showed a decrease in heart rate after traction on the eye muscles. The occurrence of the oculocardiac reflex, the amount of gastric content, and the number of muscles operated on had no influence on the incidence of PONV.
In the placebo group, the overall incidence of postoperative vomiting was 60.1% compared with 30.7% in the treatment group (P < 0.0001). The highest efficacy of dimenhydrinate was observed in the interval 3–6 h after extubation (Figure 1). In the periods 0–3 h after extubation and 12–18 h after extubation, no effect of dimenhydrinate was observed. Dimenhydrinate suppositories led to significantly lower requirements of rescue medication (P < 0.001) (Table 2). The administration of dimenhydrinate was associated with a significantly longer stay in the recovery room (P = 0.001). Furthermore, children in the treatment group were found to have significantly lower Steward scores at discharge (P = 0.033) than children who received the placebo preparation (Table 2).
Preanesthetic medication was classified as “excessive” in five children in the treatment group and in one child who received the placebo. However, evaluation of preanesthetic medication did not differ significantly between the groups (P = 0.0684). In one patient who received dimenhydrinate, a prolonged recovery from anesthesia was observed. This child needed intermittent mask ventilation as a result of insufficient spontaneous respiration, and despite monitoring in the recovery room for 300 min, the Steward score at discharge was still below average.
Postoperative vomiting continues to be a problem after strabismus surgery in children. Our study demonstrates that rectal application of 2–3 mg/kg body weight dimenhydrinate given 30 minutes before the induction of anesthesia leads to approximately a 50% relative decrease of PONV and significantly reduces requirements for rescue medication during the first 12 hours after surgery, compared with placebo.
Several therapies have proven effective for treatment and prevention of PONV. Rose et al. (4) evaluated the antiemetic efficacy of odansetron and metoclopramide in children undergoing strabismus surgery and found a reduction of PONV from 67% in the placebo group to 53% in the metoclopramide group and 30% in the odansetron group. Compared with our results, IV odansetron was only slightly more effective in reducing PONV than dimenhydrinate, whereas metoclopramide was markedly less effective. IV and oral application of droperidol were also found to lead to a significant reduction of PONV (5,6). However, the minimal effective dose without sedative side effects is still under discussion (11,12). Although in our study no direct comparison between commonly used antiemetics and dimenhydrinate was made, we conclude that dimenhydrinate suppositories are an effective drug for the prophylaxis of PONV.
Sedation is a common effect associated with the application of dimenhydrinate. In our study, the time to discharge from the recovery room was prolonged in children who received dimenhydrinate and correlated with a lower Steward score. These results are in contrast to the study of Vener et al. (13), who compared the IV administration of 0.5 mg/kg dimenhydrinate in children undergoing eye muscle surgery with that of a placebo. Although he found a reduction of overall incidence of PONV from 65% to 30%, comparable to our results, he found no delay in arousal, discharge from the recovery room, or discharge from the hospital after the IV administration of dimenhydrinate. In our investigation, a larger dose of 2–3 mg/kg dimenhydrinate, which is recommended for rectal application, was used. The pharmakokinetic differences after IV versus rectal application may provide an explanation for the sedative effects we observed. This pharmokokinetic profile may also lead to maximal effects in the time intervals 3–6, 6–9, and 9–12 hours after extubation, whereas up to 3 hours and more than 12 hours after surgery, no significant differences between treatment and placebo were observed.
Based on the longer recovery times as well as the lower arousal scores, the prophylactic administration of rectal dimenhydrinate is thought to be associated with higher costs because of nursing care and prolonged stay in the recovery room. The IV administration of dimenhydrinate or application of alternative drugs, such as 5-hydroxytryptamine antagonists, which do not delay recovery, may be more favorable to prevent PONV. Although treatment with 5-hydroxytryptamine antagonists is still expensive compared with dimenhydrinate application, these higher medication costs may be outweighed by increased nursing costs associated with prolonged recovery.
Our study demonstrates that rectal application of dimenhydrinate is effective in reducing PONV and may especially be useful in the later postoperative period and after discharge from the hospital when IV access is no longer available. However, the ideal concentration to avoid excessive sedation still needs to be evaluated. Further studies are necessary to assess whether repeated administration of dimenhydrinate may be useful in the prevention and treatment of early as well as late PONV in the postoperative period after strabismus surgery. Further studies are also necessary to directly compare dimenhydrinate with 5-hydroxy-tryptamine antagonists.
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© 2000 International Anesthesia Research Society
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