Lynne M. Reynolds

The Safety and Efficacy of Sevoflurane Anesthesia in Infants and Children with Congenital Heart Disease

We tested the hypothesis that sevoflurane is a safer and more effective anesthetic than halothane during the induction and maintenance of anesthesia for infants and children with congenital heart disease undergoing cardiac surgery. With a background of fentanyl (5 &mgr;g/kg bolus, then 5 &mgr;g · kg−1 · h−1), the two inhaled anesthetics were directly compared in a randomized, double-blinded, open-label study involving 180 infants and children. Primary outcome variables included severe hypotension, bradycardia, and oxygen desaturation, defined as a 30% decrease in the resting mean arterial blood pressure or heart rate, or a 20% decrease in the resting arterial oxygen saturation, for at least 30 s. There were no differences in the incidence of these variables; however, patients receiving halothane experienced twice as many episodes of severe hypotension as those who received sevoflurane (P = 0.03). These recurrences of hypotension occurred despite an increased incidence of vasopressor use in the halothane-treated patients than in the sevoflurane-treated patients. Multivariate stepwise logistic regression demonstrated that patients less than 1 yr old were at increased risk for hypotension compared with older children (P = 0.0004), and patients with preoperative cyanosis were at increased risk for developing severe desaturation (P = 0.049). Sevoflurane may have hemodynamic advantages over halothane in infants and children with congenital heart disease.

Influence of sensor site location on pulse oximetry kinetics in children.

A pulse oximeter sensor is used to monitor changes in arterial hemoglobin oxygen saturation (SpO2) in anesthetized pediatric patients. The authors compared the kinetics of desaturation and resaturation measured by sensors placed over central (tongue, cheek) and peripheral (finger, toe) vascular beds in children with congenital heart disease. Desaturation time was defined as the time which elapsed between the onset of apnea and a 4% decrease in SpO2 from baseline. The desaturation times averaged 24 +/- 12 s, 56 +/- 34 s, and 58 +/- 28 s for the cheek, finger, and toe, respectively (n = 40; P < 0.0001 for cheek versus finger or toe). Resaturation time was defined as the interval between the resumption of ventilation and a 4% increase in SpO2 above the nadir. Resaturation times averaged 12 +/- 8 s for the cheek, 40 +/- 36 s for the finger, and 47 +/- 25 s for the toe (n = 40; P < 0.0001 for cheek versus finger or toe). A comparison of the kinetics at two central sensor sites, cheek and tongue, respectively, revealed no significant differences in desaturation times (20 +/- 10 s vs 21 +/- 9 s) or resaturation times (10 +/- 6 s vs 7 +/- 3 s) (n = 13). The authors conclude that both desaturation and resaturation are detected earlier by centrally placed sensors.

Bioavailability of Intramuscular Rocuronium in Infants and Children

Background: Intramuscular rocuronium, in doses of 1,000 micro gram/kg in infants and 1,800 micro gram/kg in children, produces complete twitch depression in 5–6 min. To determine the rate and extent of absorption of rocuronium after intramuscular administration, blood was sampled at various intervals after rocuronium administration by both intramuscular and intravenous routes to determine plasma concentrations (Cp) of rocuronium. Methods: Twenty‐nine pediatric patients ages 3 months to 5 yr were anesthetized with N2 O and halothane. The trachea was intubated, ventilation was controlled, and adductor pollicis twitch tension was measured. When anesthetic conditions were stable, rocuronium (1,000 micro gram/kg for infants and 1,800 micro gram/kg for children) was injected either intramuscularly (in the deltoid muscle) or intravenously. Four venous plasma samples were obtained from each child 2–240 min after rocuronium administration. A mixed‐effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak Cp with intramuscular administration. Results: With intramuscular administration, rocuroniums bioavailability averaged 82.6% and its absorption rate constant was 0.105 min sup ‐1. Simulation indicated that Cp peaked 13 min after rocuronium was given intramuscularly, and that 30 min after intramuscular administration, less than 4% of the administered dose remained to be absorbed from the intramuscular depot. Conclusions: After rocuronium is administered into the deltoid muscle, plasma concentrations peak at 13 min, and approximately 80% of the administered drug is absorbed systemically.

Prolonged spontaneous movement following emergence from propofol/nitrous oxide anesthesia.

Propofol is an anesthetic used for induction and maintenance of general anesthesia (1) and for sedation during monitored anesthesia care (2). Spontaneous motor movement frequently occurs (3,4) and transient opisthotonos occasionally occurs (5) during induction of general anesthesia with propofol. Unresponsiveness lasting 5 h, transient opisthotonos, and transient tonic-clonic motor activity, all associated with altered patient mental status, have been described during the recovery period following surgical procedures lasting less than 20 min for which propofol was the drug used for induction of anesthesia (6). We present a patient who, despite an intact mental status, experienced new onset of involuntary myoclonic-dystonic motor movement which lasted several days following emergence from a propofol/nitrous oxide anesthetic.

Pharmacokinetics of rapacuronium in infants and children with intravenous and intramuscular administration

Background A nondepolarizing muscle relaxant with an onset and offset profile similar to succinylcholine is desirable for pediatric anesthesia. The onset and offset of rapacuronium are rapid in children. In the current study, the authors determined its pharmacokinetic characteristics in children. In addition to administering rapacuronium by the usual intravenous route, the authors also gave rapacuronium intramuscularly to determine uptake characteristics and bioavailability. Methods Forty unpremedicated patients aged 2 months to 3 yr were anesthetized with halothane, 0.82–1.0% end-tidal concentration. When anesthetic conditions were stable, rapacuronium was injected either into a peripheral vein (2 mg/kg for infants, 3 mg/kg for children) or a deltoid muscle (2.8 mg/kg for infants, 4.8 mg/kg for children). Four venous plasma samples were obtained from each subject 2–240 min after rapacuronium administration. A mixed-effects population pharmacokinetic analysis was applied to these values to determine bioavailability, absorption rate constant, and time to peak plasma concentration with intramuscular administration. Results Plasma clearance was 4.77 ml · kg−1 · min−1 + 8.48 ml/min. Intramuscular bioavailability averaged 56%. Absorption from the intramuscular depot had two rate constants: 0.0491 min−1 (72.4% of absorbed drug) and 0.0110 min−1 (27.6% of the absorbed drug). Simulation indicated that plasma concentration peaks 4.0 and 5.0 min after intramuscular rapacuronium in infants and children, respectively, and that, at 30 min, less than 25% of the administered dose remains to be absorbed from the intramuscular depot. Conclusions In infants and children, rapacuronium’s clearance and steady state distribution volume are less than in adults. After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min.

Intramuscular Rocuronium in Infants and Children: Dose-Ranging and Tracheal Intubating Conditions

Background Rocuroniums rapid onset and intermediate duration of action with intravenous administration suggests that intramuscular administration might facilitate tracheal intubation without producing prolonged paralysis. Accordingly, in infants and children, the authors measured onset at the adductor pollicis and respiratory muscles to determine the optimal dose (phase I), then gave this optimal dose to determine the optimal time for tracheal intubation (phase II). Methods The authors studied 45 unpremedicated patients aged 3 months to 5 yr. In phase I, 25 patients were anesthetized with nitrous oxide and halothane and breathed spontaneously; twitch tension and minute ventilation were measured. Rocuronium (800–2,400 micro gram/kg) was injected into the quadriceps or deltoid muscle; doses varied, using an “up‐down” technique, the goal being to bracket the dose depressing twitch 75–90% within 5 min. In phase II, deltoid injections of the optimal dose from phase I (infants: 1,000 micro gram/kg; children: 1,800 micro gram/kg) were given to 20 patients anesthetized with 0.82–1.0% halothane. Tracheal intubation was attempted 1.5–3.0 min later; time to tracheal intubation was varied, using an “up‐down” technique. Results In phase I, 5 of 7 patients given quadriceps injections (1,200–2,200 micro gram/kg) had slow onset of twitch and ventilatory depression. With deltoid injections (800–2,400 micro gram/kg), all patients developed complete twitch depression; median time to 50% depression of minute ventilation was 3.2 min in infants and 2.8 min in children. In phase II, intubating conditions were consistently adequate or good‐excellent at 2.5 min in infants and 3.0 min in children. Initial twitch recovery was at 57+/‐13 min (mean+/‐SD) in infants and 70+/‐23 min in children. Conclusions Deltoid injections of rocuronium, 1,000 micro gram/kg in infants and 1,800 micro gram/kg in children, rapidly permit tracheal intubation in infants and children, despite a light plane of anesthesia. Duration of action of these large doses might limit clinical utility.

Desmopressin Does Not Decrease Bleeding after Cardiac Operation in Young Children

Young children undergoing complex cardiac operation lose more blood after cardiopulmonary bypass than do older patients. This study was designed to investigate the effect of desmopressin on blood loss during the first 24 hours after cardiac operation in children undergoing principally complex surgical procedures. The study consisted of a randomized, blinded comparison of 112 pediatric patients who received either desmopressin 0.3 microgram/kg or saline solution placebo after cardiopulmonary bypass. A coagulation profile including bleeding time, quantitation of von Willebrand factor, and qualitative analysis of the factor VII:von Willebrand factor complex was performed before, 30 minutes after, and 3 hours after the operation. Blood loss and blood replacement were recorded for the first 24 hours after the operation. The surgeon classified the technical difficulty of each procedure as simple or complex. Statistical analysis was performed with Students unpaired t test and chi 2 analysis. Significance was defined as p < 0.05. Results are listed as mean +/- standard deviation. Data collection was completed for 95 patients. The mean age of all patients was 26 +/- 40 months, and the mean weight was 10 +/- 11 kg, with 84% undergoing complex procedures. There were no differences between the desmopressin and placebo groups with respect to age, weight, or surgical complexity. Twenty-four-hour blood loss and replacement between the desmopressin and placebo groups were not different (blood loss: desmopressin 30 +/- 33 ml/kg, placebo 35 +/- 36; blood replacement: desmopressin 65 +/- 43 ml/kg, placebo 64 +/- 46 ml/kg). Coagulation profiles between the desmopressin and placebo groups were not different at any time. We conclude that desmopressin does not reduce blood loss or blood replacement in young children after cardiopulmonary bypass for either simple or complex cardiac surgical procedures.