Jeffrey L. Galinkin

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

BackgroundMany children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. MethodsIn phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 &mgr;g/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 &mgr;g/kg) or saline. Postoperative agitation, Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. ResultsIn phase 1, the mean fentanyl concentrations at 10 ± 4 min (mean ± SD) and 34 ± 9 min after administering intranasal fentanyl were 0.80 ± 0.28 and 0.64 ± 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. ConclusionsSerum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles

Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study’s research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after.

Subjective, psychomotor, cognitive, and analgesic effects of subanesthetic concentrations of Sevoflurane and nitrous oxide

Background: Sevoflurane is a volatile general anesthetic that differs in chemical nature from the gaseous anesthetic nitrous oxide. In a controlled laboratory setting, the authors characterized the subjective, psychomotor, and analgesic effects of sevoflurane and nitrous oxide at two equal minimum alveolar subanesthetic concentrations. Methods: A crossover design was used to test the effects of two end‐tidal concentrations of sevoflurane (0.3% and 0.6%), two end‐tidal concentrations of nitrous oxide (15% and 30%) that were equal in minimum alveolar concentration to that of sevoflurane, and placebo (100% oxygen) in 12 healthy volunteers. The volunteers inhaled one of these concentrations of sevoflurane, nitrous oxide, or placebo for 35 min. Dependent measures included subjective, psychomotor, and physiologic effects, and pain ratings measured during a cold‐water test. Results: Sevoflurane produced a greater degree of amnesia, psychomotor impairment, and drowsiness than did equal minimum alveolar concentrations of nitrous oxide. Recovery from sevoflurane and nitrous oxide effects was rapid. Nitrous oxide but not sevoflurane had analgesic effects. Conclusions: Sevoflurane and nitrous oxide produced different profiles of subjective, behavioral, and cognitive effects, with sevoflurane, in general, producing an overall greater magnitude of effect. The differences in effects between sevoflurane and nitrous oxide are consistent with the differences in their chemical nature and putative mechanisms of action.

Lidocaine Iontophoresis Versus Eutectic Mixture of Local Anesthetics (emla®) for Iv Placement in Children

Pain during venipuncture is a major source of concern to children and their caretakers. Iontophoresis is a novel technique that uses an electrical current to facilitate movement of solute ions (lidocaine) across the stratum corneum barrier to provide dermal analgesia. In this study, we compared dermal analgesia provided by lidocaine iontophoresis and eutectic mixture of local anesthetics (EMLA®). After informed consent, 26 children, aged 7–16 yr, who required venous cannulation on multiple occasions, were enrolled in this prospective, randomized, crossover study to receive EMLA and iontophoresis on separate occasions. During a third session, each subject received his or her preferred treatment. Pain during venipuncture was assessed by the subject, parent, observer, and technician performing the procedure, by use of a 100-mm visual analog scale. The observer also used the Children’s Hospital of Eastern Ontario Pain Scale to rate the subject’s pain. Ratings of subject satisfaction were also assessed. There were no significant differences between the two groups in the subject-rated visual analog scale or the Children’s Hospital of Eastern Ontario Pain Scale scores. Eleven (50%; 95% confidence interval [CI], 31%–69%) of the 22 subjects who completed both sessions preferred iontophoresis. Five subjects (23%; 95% CI, 10%–44%), including two who did not tolerate treatment with iontophoresis, preferred EMLA, and six (27%; 95% CI, 13%–48%) had no preference for the intervention to provide dermal analgesia. We conclude that lidocaine iontophoresis provides similar pain relief for insertion of IV catheters as EMLA and is a useful noninvasive alternative to establish dermal analgesia for venous cannulation.

Anaesthesia for fetal surgery

*Department of Anesthesia, Children’s Hospital, Harvard Medical School, Boston, MA,**Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia,University of Pennsylvania School of Medicine, Philadelphia and †Department of Anesthesia andCritical Care, The Hospital of the University of Pennsylvania, University of Pennsylvania Schoolof Medicine, Philadelphia, PA, USA

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis

Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

A study of lidocaine iontophoresis for pediatric venipuncture

In this randomized, double-blinded, placebo-controlled study, we evaluated the safety and efficacy of lidocaine iontophoresis for the prevention of pain associated with venipuncture in 59 children aged 6–17 yr. Children received either lidocaine HCl 2% with epinephrine 1:100,000 (Active) or the same formulation without lidocaine (Placebo) via a 20 mA/min iontophoretic treatment. Pain during venipuncture was assessed by the subject, parent, and nurse using a 100-mm visual analog scale. Median (interquartile range) visual analog scale scores were significantly lower in the Active versus Placebo groups: subject, 7.0 (2.0–20.8) versus 31.0 (12.0–48.0), P < 0.001; nurse, 5.0 (2.2–10.8) versus 24.0 (9.0–47.0), P < 0.001; and parent, 3.0 (0.8–7.2) versus 20.0 (4.5–43.0), P < 0.002, respectively. Similarly, higher median satisfaction scores were given to the Active versus Placebo group by the three evaluators. Of the 59 subjects completing the study, 10 subjects experienced a total of 12 adverse events that were all graded as mild. In conclusion, lidocaine iontophoresis is safe in children, reduces discomfort associated with venipuncture, and increases satisfaction when compared with the placebo.

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days - <21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9–259 nmol/L (0.38–108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2–282 nmol/L (0.08–117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90th percentile of race-specific reference values and apolipoprotein (a) <10th percentiles [odds ratio=14.0 (95% confidence interval: 1.0–184), P=0.05 and odds ratio=12.8 (1.61–101), P=0.02]. Statistically significant but weak correlations were observed between euglobulin lysis time and both lipoprotein (a) level (r=0.18, P=0.03) and apolipoprotein (a) size (r= −0.26, P=0.002). In conclusion, elevated lipoprotein (a) and small apolipoprotein (a) potently increase the risk of recurrent arterial ischemic stroke in children, with a mechanism only partially attributable to impaired fibrinolysis. Collaborative studies are warranted to investigate these findings further and, more broadly, to establish key risk factors for incident and recurrent arterial ischemic stroke in children.

Anesthesia for Fetoscopic Fetal Surgery: Twin Reverse Arterial Perfusion Sequence and Twin-Twin Transfusions Syndrome

IMPLICATIONS Twin reversed arterial perfusion sequence and twin-twin transfusion syndrome can be managed by fetoscopic fetal surgery. It is important to consider the fetal, uteroplacental, and maternal issues when choosing an anesthetic technique. We report on three patients with differing anesthetic issues using fetoscopic surgery for umbilical cord coagulation.

A low blood volume LC‐MS/MS assay for the quantification of fentanyl and its major metabolites norfentanyl and despropionyl fentanyl in children

Preterm and term neonates often require surgical procedures and analgesia. However, our knowledge about neonatal pharmacokinetics of fentanyl, the most commonly used drug for these procedures, and its metabolites is still incomplete. To facilitate pharmacokinetic studies of fentanyl and its metabolites in neonates and other children, we developed and validated an LC-MS/MS method based on minimally invasive, low blood volume sampling. LC-MS/MS was used for the simultaneous analysis of fentanyl, despropionyl fentanyl (DPF), and norfentanyl from dried blood samples (DBS) collected on filter paper. Positive ions were monitored using multiple reaction monitoring. Since the standard matrix for measuring fentanyl blood concentrations is plasma, the assay was developed and validated in plasma, whole blood, and then DBS. Our method was able to measure clinically relevant levels of fentanyl and its metabolites. In DBS, the lower limits of quantification were 100 pg/mL for fentanyl with a range of reliable response from 0.1 to 100 ng/mL (r(2)>0.99) and 250 pg/mL for both DPF and norfentanyl with a range of reliable response from 0.25 to 100 ng/mL (r(2)>0.99). In plasma and in DBS inter-day accuracy and precisions of fentanyl met predefined acceptance criteria and also indicated comparable assay performance in both matrices.