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PEDIATRIC ANESTHESIA

Postoperative Nausea and Vomiting in Children and Adolescents Undergoing Radiofrequency Catheter Ablation: A Randomized Comparison of Propofol- and Isoflurane-Based Anesthetics

Thomas O. Erb, MD MHS^*, Janet M. Hall, CRNA^*, Richard J. Ing, MD^*, Ronald J. Kanter, MD, Frank H. Kern, MD^*, Scott R. Schulman, MD^*, and Tong J. Gan, MD^*

Departments of *Anesthesiology and Pediatric Cardiology, Duke University, Durham, North Carolina

Address correspondence and reprint requests to Thomas O. Erb, MD, MHS, Department of Anesthesiology, University Children’s Hospital, Roemergasse 8, Basel, CH-4058, Switzerland. Address e-mail to thomas.erb{at}unibas.ch

	Abstract

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In children, radiofrequency catheter ablation (RFCA) is typically performed under general anesthesia. With the use of volatile anesthetics, postoperative nausea and vomiting (PONV) are common, with an incidence of emesis as frequent as 60%. We tested the hypothesis that a propofol (PRO)-based anesthetic would have a less frequent incidence of PONV than an isoflurane (ISO)-based anesthetic. Patients were randomly assigned to receive either an ISO- or PRO-based anesthetic. Prophylactic ondansetron was given to all patients and droperidol was used as a rescue antiemetic postoperatively while PONV was monitored postoperatively for 18 h. The incidence of nausea, vomiting, use of rescue antiemetic drugs, and sedation scores were recorded. The cost for the anesthetic was also calculated. Fifty-six subjects were included in this study. The cumulative incidence of PONV was significantly more frequent in group ISO (63% nausea/55% emesis) compared with group PRO (21% nausea/6% emesis). After the administration of droperidol, further vomiting occurred in 70% of the patients in group ISO versus 0% of the patients in group PRO. We conclude that RFCA using ISO has a high PONV risk and the prophylactic use of ondansetron as well as antiemetic therapy with droperidol are ineffective. In contrast, a PRO-based anesthetic is highly effective in preventing PONV in children undergoing RFCA.

IMPLICATIONS: In children undergoing radiofrequency catheter ablation and receiving prophylactic ondansetron, a frequent incidence (60%) of postoperative vomiting was observed under an isoflurane-based anesthetic, whereas the incidence was significantly reduced to a very low level (5%) under a propofol-based anesthetic.

	Introduction

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In children, radiofrequency catheter ablation (RFCA) is a highly effective treatment for supraventricular tachycardia (1,2). General anesthesia is often required to ensure comfort during the prolonged procedure and to assure immobility in order to facilitate accurate mapping and subsequent ablation of the accessory pathway and/or arrhythmogenic focus (3).

Postoperative nausea and vomiting (PONV) is a common problem in children and adolescents undergoing RFCA using volatile anesthetics, with an incidence of emesis as frequent as 60%. We speculated that the administration of propofol (PRO) could effectively reduce PONV in this population as has been previously shown in other groups at high risk of PONV (4). Therefore, we performed a randomized trial to test the hypothesis that a PRO-based anesthetic would have a less frequent incidence of PONV than an isoflurane (ISO)-based anesthetic.

	Materials and Methods

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Patients
After IRB approval and written parental informed consent and, when appropriate, the participant’s assent was also obtained, 56 patients aged 4 to 18 yr admitted to undergo RFCA were included in this study. Subjects with contraindications to the use of either PRO or ISO were excluded. Patients were randomly allocated to receive PRO or ISO. Blocked randomization was generated by using computer random numbers. All patients included in the present study were part of a study evaluating electrophysiologic effects of PRO and ISO in which sustained supraventricular tachycardia was induced successfully with the initially assigned drug (5).

Anesthesia
Preanesthetic medication consisted of midazolam given either orally (0.5 mg/kg up to a maximum of 10 mg) or IV (2 mg) when IV access was established before the induction of anesthesia. Routine monitoring included electrocardiography, noninvasive blood pressure measurement, and pulse oximetry. In all patients, anesthesia was induced by inhaling sevoflurane via a face mask. Pancuronium (0.1 mg/kg) was used to facilitate endotracheal intubation, and fentanyl (2–4 µg/kg) was administered before laryngoscopy. After tracheal intubation, sevoflurane was discontinued. Thereafter, anesthesia was maintained with the assigned study drug (PRO or ISO) in a mixture of 66% nitrous oxide and 33% oxygen. Real-time bispectral index (BIS) data were obtained via electroencephalogram electrodes through a frontotemporal montage (BIS^TM sensor; Aspect Medical Systems, Newton, MA) and the electroencephalogram activity was recorded by using an Aspect 1050, version 3.3 (Aspect Medical Systems) (6). Dosage of the study drugs was adjusted to maintain the BIS within a range of 50–60. Pancuronium was used as the neuromuscular drug during the intraoperative period.

RFCA Procedures
Details of the electrophysiologic procedure in these patients are reported elsewhere (5). Briefly, first a diagnostic electrophysiologic study was performed to identify the tachycardia and to map the critical substrate. After conclusion of the diagnostic study, ablation of the pathological substrate(s) was performed by using radiofrequency energy. Then, a final diagnostic electrophysiologic study was performed. All patients received isoproterenol (0.03–0.07 µg · kg^-1 · min^-1) at least once during the procedure.

Approximately 30 min before the conclusion of the procedure, all patients received ondansetron (0.1 mg/kg up to 4 mg), ketorolac (0.5 mg/kg up to 30 mg), followed by neostigmine (40 µg/kg) and glycopyrrolate (8 µg/kg) to antagonize neuromuscular blockade. Stomach contents were suctioned from each patient with an orogastric tube.

Postprocedural Care
Postprocedural care was provided in the recovery room. The incidences of postoperative nausea and retching or vomiting were recorded at time intervals of 0.5, 2, and 18 h by a nurse or research assistant trained in the assessment of PONV symptoms and who were unaware of the patient’s treatment group. Nausea was defined as feeling the urge to vomit and vomiting was defined as expulsion of stomach contents through the mouth. Retching was defined as an attempt to vomit, not productive of stomach contents. Droperidol (20 µg/kg) was used as a rescue antiemetic in patients with vomiting (first episode), retching, or at a patient’s request. Vital signs (arterial blood pressure measured by an indwelling arterial catheter, heart rate, respiratory rate) and observer assessment of sedation scores (7) were recorded at 0, 15, 30, 60, and 90 min after patient admission to the postanesthesia care unit. A patient was ready for discharge from the postanesthesia care unit when the following criteria were met: hemodynamically stable; protective reflex present—patient fully conscious and able to protect own airway; pain controlled; absence of severe nausea or active vomiting; skin warm and dry. All patients were then admitted to the ward and discharged from the hospital the next day.

Costs
The cost was calculated as follows: ISO according to the formula by Dion (8) at a price of $19.74/100 mL, and PRO in 200-mg steps at a price of $10.24/200 mg.

A sample size of 28 patients in each group provided a power of 85% to detect a PONV risk reduction of 50% between the two treatments: this would be a reduction from 60% (expected in group ISO) to 30% [expected in group PRO (4)]. Continuous data were analyzed by Student’s t-test and nominal data were analyzed by using Fisher’s exact test. Repeated measurements (hemodynamic variables and sedation scores during the stay in the postanesthesia unit) were analyzed by using mixed models (SAS System 6.12; SAS Institute, Cary, NC). A probability value <0.05 was considered statistically significant.

	Results

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Demographic data of the 56 subjects included in the study are shown in Table 1. The patient’s characteristics were similar in both groups with a predominance of males. Total anesthesia time was not different between the two groups (group ISO 317 ± 88 min versus group PRO 319 ± 97 min).

The incidence of postoperative nausea at 0.5, 2, and 18 h and the incidence of vomiting were statistically significantly less in group PRO compared with group ISO (Table 2). In Group ISO, patients had an early onset of PONV during the first 3 h after termination of the anesthesia. In contrast, the onset of PONV in group PRO was delayed (Fig. 1).

View larger version (15K): [in this window] [in a new window]   Figure 1. Survival curve for postoperative vomiting. Proportion refers to the fractional proportion of patients without an episode of vomiting (log-rank test P < 0.001)

View larger version (13K): [in this window] [in a new window]   Figure 2. Sedation scores in the postanesthesia care unit. Values are expressed as mean ± SD using modified observer’s assessment of alertness/sedation scale. There were no statistically significant differences between the groups (SAS® MIXED procedure for repeated measures analyses P = 0.12).

	Discussion

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In the present study, the incidence of PONV in patients receiving ISO was 63% despite prophylaxis with ondansetron 30 min before the end of anesthesia. In addition, after the use of droperidol, when administered as a rescue antiemetic, recurrent vomiting was observed in 70% of patients receiving ISO-based anesthesia, suggesting that PONV prophylaxis with ondansetron and PONV treatment with droperidol might not be effective in this population.

Compared with ISO, PRO-based anesthetics have been associated with a less frequent incidence of PONV (4,9). In a pharmacokinetic PRO simulation of the postoperative period, Gan et al. (4,10) showed that where PRO was used throughout the procedure (duration, 2.4 ± 1.3 hours; dose range, 50–150 µg · kg^-1 · min^-1), the calculated average concentration was in a range known to reduce PONV effectively up to six hours. In our study, a similar dose range of the administered PRO (Table 1) was used; however, the duration of propofol administration was longer when compared with that in the study by Gan et al. (4).

The postoperative antiemetic effect lasting up to 18 hours in the PRO group in the present study could have resulted from the combination of ondansetron and PRO enhancing the antiemetic effects, even though ondansetron has a relatively short half-life of approximately 3 hours (11) and the antiemetic effect persists for 4 to 6 hours after a single preventive dose (4). When combining preventive ondansetron with PRO in children undergoing tonsillectomy, Barst et al. (12) found a very small emesis incidence of 7% in the 24-hour period after surgery, which contrasted with an incidence of 22% when PRO was given alone (12). Whether the similarly small incidence of PONV achieved in our study in group PRO was the result of the combination of these two antiemetic drugs or related to the long-lasting administration of PRO alone remains unknown. However, there are numerous studies demonstrating increased efficacy for the prevention of PONV when combination antiemetics versus a single drug were used (13).

Patients undergoing RFCA under general anesthesia represent a unique population in several ways. RFCA is not a painful procedure; in this study, fentanyl was given in small doses predominantly at the induction of anesthesia and nonsteroidal antiinflammatory drugs were given at the end of the procedure and in the postoperative period. Thus, opioids did not have a significant role in this setting. All patients included in this were kept immobile in bed after the procedure until the next morning, reducing the effects of motion-induced sickness. Hence, we speculate that the frequent incidence of PONV in patients receiving ISO was primarily related to the long duration of combined application of the volatile anesthetics ISO and nitrous oxide (14,15).

The smaller incidence of PONV with PRO came with additional costs, but because there are no clinically relevant differences regarding the electrophysiologic properties between these drugs in patients undergoing RFCA (5), the favorable outcome regarding PONV may justify the use of PRO. Complete cost assessment should also include the costs associated with episodes of emesis, which were not evaluated in this study, and patients’ and parents’ satisfaction with the perioperative course were not assessed. A study in adults demonstrated that patients themselves are willing to pay an extra median amount of $56–$100 to avoid PONV (16). Another study evaluating parents’ willingness to pay extra for reducing the incidence of postoperative emesis in their children found the median amount to be Br £50 (approximately US $75), 95% confidence interval: Br £20–80 (17).

Several limitations of the present study must be noted. First, assessment of nausea is difficult in children, but because only one subject was a preschool-aged child, we consider that the information gathered accurately reflected the presence or absence of nausea. Second, no placebo control is available in this study. Therefore, the potential effect of the prophylactic use of ondansetron in this population remains unknown. Third, an inhaled induction with sevoflurane was used in all patients in this study. However, the short lasting use of this anesthetic at the beginning of the procedure most likely did not confound the findings in our study. Fourth, droperidol, which was used as a rescue antiemetic drug in this study, has been subject to a recent Food and Drug Administration "black box" warning that might also limit its use in the pediatric population, although none of the reported cases implicating droperidol were in children (18).

In conclusion, children and adolescents undergoing RFCA under general anesthesia with ISO had a frequent incidence of PONV although ondansetron was given prophylactically. The use of a PRO-based anesthetic reduced the incidence to very low levels, although costs were higher.

	Acknowledgments

 
This work has been supported exclusively by institutional assistance, Department of Anesthesiology, Duke University, Durham, NC.

The Aspect 1050 and data logging system used in this study were generously provided by Aspect Medical Systems, Newton, MA. The authors thank Joan Etlinger, BA (Department of Anesthesiology, University of Basel, Switzerland), for her help with manuscript preparation.

	Footnotes

 
Presented in part at the Society for Pediatric Anesthesia Spring Meeting 2001, San Diego, CA, February 25, 2001.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Erb, T. O. Articles by Gan, T. J. Search for Related Content PubMed PubMed Citation Articles by Erb, T. O. Articles by Gan, T. J. Related Collections Cardiovascular Postanesthetic Care Unit Pediatrics Pharmacology