Dexmedetomidine Pharmacokinetics and a New Dosing Paradigm in Infants Supported With Cardiopulmonary Bypass.

BACKGROUND: Dexmedetomidine is increasingly used off-label in infants and children with cardiac disease during cardiopulmonary bypass (CPB) and in the postoperative period. Despite its frequent use, optimal dosing of dexmedetomidine in the setting of CPB has not been identified but is expected to differ from dosing in those not supported with CPB. This study had the following aims: (1) characterize the effect of CPB on dexmedetomidine clearance (CL) and volume of distribution (V) in infants and young children; (2) characterize tolerance and sedation in patients receiving dexmedetomidine; and (3) identify preliminary dosing recommendations for infants and children undergoing CPB. We hypothesized that CL would decrease, and V would increase during CPB compared to pre- or post-CPB states. METHODS: Open-label, single-center, opportunistic pharmacokinetics (PK) and safety study of dexmedetomidine in patients ≤36 months of age administered dexmedetomidine per standard of care via continuous infusion. We analyzed dexmedetomidine PK data using standard nonlinear mixed effects modeling with NONMEM software. We compared model-estimated PK parameters to those from historical patients receiving dexmedetomidine before anesthesia for urologic, lower abdominal, or plastic surgery; after low-risk cardiac or craniofacial surgery; or during bronchoscopy or nuclear magnetic resonance imaging. We investigated the influence of CPB-related factors on PK estimates and used the final model to simulate dosing recommendations, targeting a plasma concentration previously associated with safety and efficacy (0.6 ng/mL). We used the Wilcoxon rank sum test to evaluate differences in dexmedetomidine exposure between infants with hypotension or bradycardia and those who did not develop these adverse events. RESULTS: We collected 213 dexmedetomidine plasma samples from 18 patients. Patients had a median (range) age of 3.3 months (0.1-34.0 months) and underwent CPB for 161 minutes (63-394 minutes). We estimated a CL of 13.4 L/h/70 kg (95% confidence interval, 2.6-24.2 L/h/70 kg) during CPB, compared to 42.1 L/h/70 kg (95% confidence interval, 38.7-45.8 L/h/70 kg) in the historical patients. No specific CPB-related factor had a statistically significant effect on PK. A loading dose of 0.7 µg/kg over 10 minutes before CPB, followed by maintenance infusions through CPB of 0.2 or 0.25 µg/kg/h in infants with postmenstrual ages of 42 or 92 weeks, respectively, maintained targeted concentrations. We identified no association between dexmedetomidine exposure and selected adverse events (P = .13). CONCLUSIONS: CPB is associated with lower CL during CPB in infants and young children compared to those not undergoing CPB. Further study should more closely investigate CPB-related factors that may influence CL.

A Randomized Controlled Trial to Determine the Effect of Depth of Anesthesia on Emergence Agitation in Children.

BACKGROUND: The cause of emergence agitation (EA) in children is unknown. Rapid emergence from inhaled anesthesia has been implicated because EA is more common with sevoflurane than with halothane. A dose-dependent effect of sevoflurane, which increases seizure-like electroencephalogram activity, has also been proposed. METHODS: To determine whether depth of anesthesia as measured by bispectral index (BIS) affects EA, 40 ASA physical status I to II children aged 2 to 8 years undergoing ophthalmic surgery were enrolled in a blinded randomized controlled trial of low-normal (40-45, deep) versus high-normal (55-60, light) anesthesia. To distinguish transient irritability from severe EA, the primary outcome was first-stage postanesthesia care unit (PACU I) peak Pediatric Assessment of Emergence Delirium (PAED) score, with secondary outcomes of PAED and Face, Legs, Activity, Cry, and Consolability scores at emergence, postoperative fentanyl dose, emergence time, and discharge time. Subjects received a standard anesthesia protocol with oral midazolam followed by mask induction with sevoflurane 8%, fentanyl 1 to 1.5 µg/kg IV (then as needed), neuromuscular blockade, and endotracheal intubation. Providers titrated expired sevoflurane (in N2O 67%) from 0.5% to 3% to maintain BIS range. PAED, Richmond Agitation Sedation Scale, and Face, Legs, Activity, Cry, and Consolability scores were measured at emergence, at PACU I arrival, and during PACU I stay. RESULTS: There was little difference between the groups in the primary outcome, peak PACU I PAED score (light: 7.7 ± 4.6; deep: 8.6 ± 5.3; mean difference, 0.9; 95% confidence interval, 4.1 to -2.3; effect size, 0.18). Discharge times were similar between groups. Treatment for severe EA was rare. CONCLUSIONS: There was no significant effect of BIS-guided deep versus light anesthesia on severe EA.

Pharmacokinetics of intravenous sildenafil in children with palliated single ventricle heart defects: effect of elevated hepatic pressures.

UNLABELLED: Aims Sildenafil is frequently prescribed to children with single ventricle heart defects. These children have unique hepatic physiology with elevated hepatic pressures, which may alter drug pharmacokinetics. We sought to determine the impact of hepatic pressure on sildenafil pharmacokinetics in children with single ventricle heart defects. METHODS: A population pharmacokinetic model was developed using data from 20 single ventricle children receiving single-dose intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect modelling was used for model development, and covariate effects were evaluated based on estimated precision and clinical significance. RESULTS: The analysis included a median (range) of 4 (2-5) pharmacokinetic samples per child. The final structural model was a two-compartment model for sildenafil with a one-compartment model for des-methyl-sildenafil (active metabolite), with assumed 100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of des-methyl-sildenafil (1.94×(hepatic pressure/9)(-1.33) L/hour/kg) was predicted to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ⩾10 versus <10 mmHg (median area under the curve=533 versus 792 µg*h/L). Discussion Elevated hepatic pressure delays clearance of the sildenafil metabolite - des-methyl-sildenafil - and increases drug exposure. We speculate that this results from impaired biliary clearance. Hepatic pressure should be considered when prescribing sildenafil to children. These data demonstrate the importance of pharmacokinetic assessments in patients with unique cardiovascular physiology that may affect drug metabolism.

A hemodynamic model to guide blood pressure control during deliberate hypotension with sodium nitroprusside in children.

Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age, and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose-ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. A total of 3464 MAP measurements collected from 202 patients during the study's blinded phase, including baseline measurements up to 6 min prior to the blinded were available for analysis. A population K-PD model was developed with a one-compartment model assumed for SNP. Size differences in CL and V of the effect compartment were described using theory-based allometry. An inhibitory sigmoidal Emax model was used to describe the effect of SNP. A power function of age was used to describe age-related differences in baseline MAP. A mixture model of two groups with low and high EC50 was used to explain variability in MAP response. Change in MAP was characterized by a linear disease progression slope during the blinded phase. In the final population model, CL and V increased with weight, and baseline MAP increased with age. The effect compartment half-life of SNP was 13.4 min. The infusion rate producing 50% of Emax (ER50) at steady state for high EC50, was 0.34 µg/kg/min and for low EC50 0.103 µg/kg/min. The K-PD model well-describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP.

Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

PURPOSE: (1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure. METHODS: We conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients <17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 µg/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect. RESULTS: The final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p ≤ 0.009 and p ≤ 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 µg/kg/min. CONCLUSION: We determined that 0.3 µg/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 µg/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668.

Safety and efficacy of sodium nitroprusside during prolonged infusion in pediatric patients.

OBJECTIVE: Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children. DESIGN: Randomized, double-blind withdrawal to placebo study. SETTING: ICUs. PATIENTS: Pediatric patients younger than 17 years. INTERVENTIONS: Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes. MEASUREMENTS AND MAIN RESULTS: The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 µg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanide toxicity. CONCLUSIONS: Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.

Predictors of arterial blood pressure control during deliberate hypotension with sodium nitroprusside in children.

BACKGROUND: Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control. METHODS: One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical process control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors. RESULTS: BP was controlled an average 45.4% (SD 23.9%; 95% CI, 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 µg·kg·min increase in average titration size, P = 0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1-mm Hg increase in MAP difference, P = 0.0013). Both effects persisted in multivariable models. CONCLUSIONS: SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although 2 inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population.

A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates.

OBJECTIVE: To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥ 28 to ≤ 44 weeks gestational age. STUDY DESIGN: Forty-two intubated, mechanically ventilated patients (n = 42) were grouped by gestational age into group I (n = 18), ≥ 28 to <36 weeks, and group II (n = 24), ≥ 36 to ≤ 44 weeks. Within each age group, there were 3 escalating dose levels, including a loading dose (LD, µg/kg) followed by a maintenance dose (MD, µg · kg(-1) · h(-1)) for 6-24 hours: level 1, 0.05 LD/MD; level 2, 0.1 LD/MD; and level 3, 0.2 LD/MD. The primary endpoint was the number of patients requiring sedation as determined by the Neonatal Pain, Agitation, Sedation Scale. RESULTS: During dexmedetomidine infusion, 5% of Neonatal Pain, Agitation, Sedation Scale scores were >3, indicating agitation/pain, with 4 patients (10%) requiring more sedation and 17 (40%) requiring more analgesia. Though there was significant variability in pharmacokinetic variables, group I appeared to have lower weight-adjusted plasma clearance (0.3 vs 0.9 L · h(-1) · kg(-1)) and increased elimination half-life (7.6 vs 3.2 hours) compared with group II. Fifty-six adverse events (AEs) were reported in 26 patients (62%); only 3 AEs (5%) were related to dexmedetomidine. There were no serious AEs and no AEs or hemodynamic changes requiring dexmedetomidine discontinuation. CONCLUSION: Dexmedetomidine is effective for sedating preterm and full-term neonates and is well-tolerated without significant AEs. Preterm neonates had decreased plasma clearance and longer elimination half-life.

Sodium nitroprusside is not associated with metabolic acidosis during intraoperative infusion in children.

BACKGROUND: Sodium nitroprusside (SNP) is a potent vasodilator that has been used to induce deliberate hypotension in children during surgery involving significant blood loss, including craniofacial and spinal fusion procedures. SNP metabolism liberates cyanide, which may cause interference with cellular energy metabolism, leading to metabolic acidosis and central nervous system injury. We performed a retrospective, case-control study to determine whether the short-term intra-operative use of SNP for deliberate hypotension is associated with metabolic acidosis in children undergoing surgical procedures for craniofacial or spinal anomalies. Cyanide and thiocyanate concentrations were also recorded in patients who received SNP. METHODS: Data from 166 children undergoing craniofacial and spinal fusion surgery between 2005 and 2010 at Lucile Packard Children's Hospital (LPCH) at Stanford were analyzed. Records from 60 patients who received SNP (SNP group) as part of a multicenter, randomized, double-blind study were compared with records from 106 eligible patients who had blood pressure reduction using anesthetic agents and did not receive SNP (control group). Metabolic acidosis was defined as serum bicarbonate (HCO3) < 18.5 mEq/L. Whole blood CN, plasma thiocyanate and urinary thiocyanate concentrations were measured in patients in the SNP group. Differences in metabolic acidosis rates between the SNP and control groups were assessed through a test of noninferiority in the rate for the SNP group with a noninferiority threshold of 0.2. A z-test was used to test the null hypothesis. The alternative hypothesis was that the difference in these rates was less than 0.2. The same noninferiority threshold of 0.2 was also used to perform separate, secondary tests for noninferiority in the proportion of patients with HCO3 levels below 18.5 mEq/L and the proportion of patients who required HCO3 administration. RESULTS: Fewer patients in the SNP group experienced metabolic acidosis compared to the control group (31.7% vs. 36.8%, respectively; p < .001). No whole blood CN levels above the lower limit of quantification were detected in any of the 51 patients with validated CN data. Plasma and urinary thiocyanate levels were also low. CONCLUSIONS: Our findings suggest that SNP, when used for short-term deliberate hypotension, does not cause an increased incidence of metabolic acidosis compared with the use of anesthetic agents alone. TRIAL REGISTRATION NUMBER: NCT00135668.

Comparison of a new cobinamide-based method to a standard laboratory method for measuring cyanide in human blood.

Most hospital laboratories do not measure blood cyanide concentrations, and samples must be sent to reference laboratories. A simple method is needed for measuring cyanide in hospitals. The authors previously developed a method to quantify cyanide based on the high binding affinity of the vitamin B12 analog, cobinamide, for cyanide and a major spectral change observed for cyanide-bound cobinamide. This method is now validated in human blood, and the findings include a mean inter-assay accuracy of 99.1%, precision of 8.75% and a lower limit of quantification of 3.27 µM cyanide. The method was applied to blood samples from children treated with sodium nitroprusside and it yielded measurable results in 88 of 172 samples (51%), whereas the reference laboratory yielded results in only 19 samples (11%). In all 19 samples, the cobinamide-based method also yielded measurable results. The two methods showed reasonable agreement when analyzed by linear regression, but not when analyzed by a standard error of the estimate or paired t-test. Differences in results between the two methods may be because samples were assayed at different times on different sample types. The cobinamide-based method is applicable to human blood, and can be used in hospital laboratories and emergency rooms.

Paraquat ingestion: a challenging diagnosis.

Paraquat is an herbicide that is highly toxic to humans. Pediatric ingestion has become uncommon in the United States because of preventative efforts. We report here an unintentional, fatal paraquat ingestion by an 8-year-old child. Storage in an inappropriate container, confusion between herbicide trade names, nonspecific symptoms, and a delay in follow-up produced challenges in the diagnosis. In the absence of a clear history of ingestion, paraquat poisoning should be suspected in children who develop skin and mucous membrane burns, gastrointestinal symptoms, acute kidney injury, and respiratory failure.

Efficacy of sedation regimens to facilitate mechanical ventilation in the pediatric intensive care unit: a systematic review.

OBJECTIVE: Children admitted to pediatric intensive care units (PICUs) often receive sedatives to facilitate mechanical ventilation. However, despite their widespread use, data supporting appropriate dosing, safety, and optimal regimens for sedation during mechanical ventilation are lacking. Therefore, we conducted a systematic review of published data regarding efficacy of sedation to facilitate mechanical ventilation in PICU patients. Our primary objective was to identify and evaluate the quality of evidence supporting sedatives used in PICUs for this purpose. DATA SOURCES: We searched MEDLINE, EMBASE, and The Cochrane Registry of Clinical Trials from 1966 to June 2008 to identify published articles evaluating sedation regimens to facilitate mechanical ventilation in PICU patients. STUDY SELECTION: We included only those studies of intubated PICU or pediatric cardiac intensive care unit patients receiving pharmacologic agents to facilitate mechanical ventilation that reported quality of sedation as an outcome. DATA EXTRACTION: We analyzed studies separately for study type and by agents being studied. Studies were appraised using criteria of particular importance for reviews evaluating sedatives. DATA SYNTHESIS: Our search strategy yielded 39 studies, including 3 randomized trials, 15 cohort studies, and 21 cases series or reports. The 39 studies evaluated a total of 39 different sedation regimens, with 21 different scoring systems, in a total of 901 PICU/cardiac intensive care unit patients ranging in age from 3 days to 19 years old. Most of the studies were small (<30 patients), and only four studies compared one or more agents to another. Few studies thoroughly evaluated drug safety, and only one study met all quality criteria. CONCLUSIONS: Despite the widespread use of sedatives to facilitate mechanical ventilation in the PICU, we found that high-quality evidence to guide clinical practice is still limited. Pediatric randomized, controlled trials with reproducible methods and assessment of drug safety are needed.

Effects of maternal nicotine exposure on branching morphogenesis of mouse fetal lung: in vivo and in vitro studies.

Epidemiological evidence suggests that premature infants born to mothers who smoke have a lower incidence of neonatal respiratory distress syndrome. The mechanism has been proposed to be due to increased lung maturity. This in vivo study investigated the effect of maternal nicotine on lung development by evaluating the airway branching morphogenesis (ABM) in mice fetuses. Nicotine (0, 2 and 3 mg/kg/day) was administered intraperitoneally to pregnant mice from gestation day 9 to day 12 (4 days). ABM was determined on day 13 by photomicrographic analysis. The results revealed a significant reduction in ABM in the higher dose nicotine group. The mean number of airway branches was 3.7 +/- 0.1/lobe for the 3 mg/kg/day group, which was smaller than 4.6 +/- 0.2/lobe for the 2 mg/kg/day nicotine group, and 4.4 +/- 0.1/lobe for the control group (F = 9.4, p < 0.001). The mean number of buds was significantly smaller in both the 2 mg/kg/day group and the 3 mg/kg/day group (8.7 +/- 0.5/lobe, 9.0 +/- 0.4/lobe vs. 12.3 +/- 0.4/lobe in the control group, F = 20.3, p < 0.001). For the in vitro study, fetal lung lobes were isolated at the 12th gestation day. The lung explants were cultured in nicotine (0, 30, 60 ng/ml) for 48 hours; there were no differences in all the groups. The results do not support the hypothesis that nicotine stimulates fetal lung ABM either in vivo or in vitro.

Mechanically ventilated pediatric stem cell transplant recipients: effect of cord blood transplant and organ dysfunction on outcome.

OBJECTIVES: To compare survival of pediatric umbilical cord blood and bone marrow transplant recipients requiring admission to a pediatric intensive care unit for mechanical ventilation and to determine the effect of organ dysfunction on outcome. DESIGN: Retrospective chart review. SETTING: Tertiary care referral center for pediatric stem cell transplants. PATIENTS: All children 0-18 yrs old admitted to the pediatric intensive care unit for mechanical ventilation after receiving a stem cell transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected from medical records of 86 patients who received a stem cell transplant and were subsequently admitted to the pediatric intensive care unit for mechanical ventilation. Demographic data were collected at the time of intubation, and physiologic data were collected at 6 hrs and 96 hrs after intubation. The pediatric intensive care unit, hospital, and 2-yr survival rates for umbilical cord blood transplant recipients were 37%, 25%, and 19%, respectively. The survival rates for bone marrow transplant recipients were 47%, 32%, and 21% for the same time periods. Umbilical cord blood and bone marrow transplant recipients with hepatic dysfunction had a significantly worse outcome, as did patients admitted for respiratory failure or sepsis. CONCLUSIONS: Pediatric recipients of an umbilical cord blood transplant who subsequently required mechanical ventilation had lower pediatric intensive care unit and hospital survival rates compared with patients receiving bone marrow transplantation. Survival at 2 yrs for umbilical cord blood transplant and bone marrow transplant patients was similar. Predictors of outcome for all stem cell transplant recipients requiring mechanical ventilation included pediatric intensive care unit diagnosis requiring intubation and hepatic function. Predictors of outcome can be identified shortly after intubation in pediatric stem cell transplant recipients and may aid in therapeutic decision making and family counseling.

Postoperative nausea and vomiting in children and adolescents undergoing radiofrequency catheter ablation: a randomized comparison of propofol- and isoflurane-based anesthetics.

UNLABELLED: 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.

Comparison of electrophysiologic effects of propofol and isoflurane-based anesthetics in children undergoing radiofrequency catheter ablation for supraventricular tachycardia.

BACKGROUND: Radiofrequency catheter ablation (RFCA), which is typically performed with general anesthesia in children, is an interventional therapy for tachyarrhythmia. Although the electrophysiologic (EP) effects of isoflurane- and propofol-based anesthetics have been shown to be similar, a retrospective analysis reported significantly longer RFCA procedural duration with the use of isoflurane. It remains unclear whether the ability to successfully perform RFCA differs between these drugs. METHODS: Patients were randomly assigned to receive either an isoflurane- or propofol-maintained anesthetic. Drug administration was titrated according to the pharmacodynamic endpoint of depth of sedation using bispectral index score. The ability to induce sustained tachycardia (using a scoring system), procedural durations, and effects on cardiac electrophysiologic properties were evaluated and compared between the groups. RESULTS: Sixty subjects were included in this study. Sustained supraventricular tachycardia (SVT) was inducible with the assigned drug in all but four subjects. In three of these four subjects, SVT was also not inducible with the alternative study drug. Ability to induce the first sustained SVT was similar between the groups (P = 0.83). Total procedural durations were similar (isoflurane 224 +/- 84 min vs. propofol 221 +/- 86 min, mean +/- SD, P = 0.88). Atrioventricular nodal conduction was slower with propofol compared with isoflurane, but this result did not appear to be clinically relevant. Finally, ventricular repolarization was prolonged by isoflurane versus propofol, the clinical significance of which was not demonstrated. CONCLUSION: Isoflurane- and propofol-based anesthesia were equally suitable in children and adolescents undergoing RFCA.

Permission and assent for clinical research in pediatric anesthesia.

IMPLICATIONS: This article discusses the process and specific nature of informed consent for clinical research in pediatric anesthesia. For informed consent to be meaningful, permission from the child's proxy must be obtained and the child's assent must be tailored in a manner that is sensitive to the abilities of children.

Evidence-based medicine in anesthesiology.

PURPOSE OF REVIEW: The principles of evidence-based medicine are now being applied in anesthesiology and intensive care medicine. The purpose of this review is to acquaint practitioners with the fundamentals of evidence-based medicine and to provide examples of how these principles can be incorporated into clinicians' practice. RECENT FINDINGS: Outcomes research utilizing evidence-based approaches are manifest in several areas of anesthesiology and intensive care medicine. Several examples are cited from various sub-specialty areas, including pediatric, obstetric, and general anesthesia, as well as intensive care medicine. SUMMARY: Evidence-based medicine is the term used to describe a practice paradigm that emphasizes the use of the best evidence available in the medical literature in making treatment decisions about the care of patients. Evidence-based approaches to care integrate individual expertise with data from externally conducted systematic research. Although evidence-based medicine has its origins in the 'treating' and 'diagnosing' specialty of internal medicine, its tenets are applicable to 'non-therapeutic' specialties such as anesthesiology and intensive care medicine. This review illustrates how evidence-based principles can be incorporated into the practice of perioperative medicine.