The halothane era in pediatric anesthesia: The convergence of a cardiac depressant anesthetic with the immature myocardium of infancy.

Introduced in the late 1950s, halothane became the anesthetic of choice for inhalational induction of children for over 40 years. Halothane enjoyed a generally favorable safety record during its time, but its cardiac contractility depressant effect-well tolerated by most age groups-was profoundly heightened in neonates and infants, leading to increased incidences of hypotension and cardiac arrest. The neonatal myocardium is immature and is characterized by poor ventricular compliance, poor contractility due to fewer contractile elements, immature sympathetic innervation with decreased norepinephrine stores, and immature mechanisms for storage and exchange of calcium in the sarcoplasmic reticulum. In vitro studies of myocardial contractility of mammalian fetal and adult myocardium demonstrated that the fetal heart was twice as sensitive to halothane as the adult. Clinical studies demonstrated that most neonates and infants less than 6 months of age experienced hypotension during halothane induction of anesthesia and significantly (p < .01) greater decreases in blood pressure than older children at equipotent concentrations of halothane. Intraoperative cardiac arrest during the halothane era occurred over twice as frequently in neonates aged less than 1 month than in infants aged 1-12 months and nearly 10 times more frequently than children 1-5 years of age. Halothane was associated with 66% of intraoperative drug-related cardiac arrests in children. The halothane era began to close in the late 1990s with the introduction of sevoflurane, which had a more favorable hemodynamic profile. Shortly thereafter, halothane was completely displaced from pediatric anesthesia practice in North America.

Labetalol Infusion Attenuates Paradoxical Hypertension and Decreases Plasma Renin Activity After Repair of Coarctation of the Aorta in Children.

OBJECTIVE: Paradoxical hypertension after repair of coarctation of the aorta in children is associated with the release of catecholamines and activation of the renin-angiotensin system. The objective of the present study was to describe the effects of labetalol infusion on blood pressure, plasma catecholamine levels, and plasma renin activity in a series of children undergoing repair of coarctation of the aorta. DESIGN: Prospective, observational cohort study. SETTING: Tertiary children's hospital with university affiliation. PARTICIPANTS: The study was comprised of 15 consecutive children older than 1 year undergoing repair of coarctation of the aorta. INTERVENTIONS: Intravenous infusion of labetalol, up to 20 µg/kg/min, was administered when patients became hypertensive after release of the aortic cross-clamp. Supplementation with nitroprusside was allowed as needed. MEASUREMENTS AND MAIN RESULTS: Blood pressure was maintained below baseline values throughout the labetalol infusion. Plasma norepinephrine increased from 160 ± 81 pg/mL (preoperative) to 657 ± 268 pg/mL (6 h after release of aortic cross-clamp). Plasma renin activity decreased from 16.6 ± 9.7 ng/kg/h (at cross-clamp release) to 2.2 ± 2.2 ng/kg/h (6 h after cross-clamp release). Nitroprusside was added for 12 patients, at a highest mean dose of 2.4 ± 2.5 µg/kg/min. CONCLUSIONS: Labetalol inhibited activation of the renin-angiotensin system and helped control paradoxical hypertension after coarctation repair in children.

Building an International Community of Paediatric Anaesthesiologists: An interview with Dr Edward Sumner.

Dr Edward Sumner (1940) enjoyed a remarkably productive career as consultant pediatric anesthetist at the Great Ormond Street Hospital for Children. His leadership in clinical care helped his department rise to eminence. He trained hundreds of registrars in pediatric anesthesia and educated thousands more through invited lectures and by co-editing leading textbooks of neonatal and pediatric anesthesia. During his long tenure as Editor-in-Chief of Pediatric Anesthesia, he led the growth of the young journal to prominence. Based on an interview and a long-standing professional and personal friendship of forty-four years, this article reviews Ted Sumner's outstanding contributions to the specialty of pediatric anesthesia and to the development of a strong international community of pediatric anesthesiologists.

Breathing circuit compliance and accuracy of displayed tidal volume during pressure-controlled ventilation of infants: A quality improvement project.

INTRODUCTION: Anesthesia machines have evolved to deliver desired tidal volumes more accurately by measuring breathing circuit compliance during a preuse self-test and then incorporating the compliance value when calculating expired tidal volume. The initial compliance value is utilized in tidal volume calculation regardless of whether the actual compliance of the breathing circuit changes during a case, as happens when corrugated circuit tubing is manually expanded after the preuse self-test but before patient use. We noticed that the anesthesia machine preuse self-test was usually performed on nonexpanded pediatric circuit tubing, and then the breathing circuit was subsequently expanded for clinical use. We aimed to demonstrate that performing the preuse self-test in that manner could lead to incorrectly displayed tidal volume on the anesthesia machine monitor. The goal of this quality improvement project was to change the usual practice and improve the accuracy of displayed tidal volume in infants undergoing general anesthesia. METHODS: There were four stages of the project: (i) gathering baseline data about the performance of the preuse self-test and using infant and adult test lungs to measure discrepancies of displayed tidal volumes when breathing circuit compliance was changed after the initial preuse self-test; (ii) gathering clinical data during pressure-controlled ventilation comparing anesthesia machine displayed tidal volume with actual spirometry tidal volume in patients less than 10 kg before (machine preuse self-test performed while the breathing circuit was nonexpanded) and after an intervention (machine preuse self-test performed after the breathing circuit was fully expanded); (iii) performing department-wide education to help implement practice change; (iv) gathering postintervention data to determine the prevalence of proper machine preuse self-test. RESULTS: At constant pressure-controlled ventilation through fully expanded circuit tubing, displayed tidal volume was 83% greater in the infant test lung (mean±SD TV 15±5 vs 9±4 mL; mean [95% CI] difference=6.3 [5.6, 7.1] mL, P<.0001) and 3% greater in the adult test lung (245±74 vs 241±72 mL; difference=5 [1, 10] mL, P=.0905) when circuit compliance had been measured with nonexpanded tubing compared to when circuit compliance was measured with fully expanded tubing. The clinical data in infants demonstrated that displayed tidal volume was 41% greater than actual tidal volume (difference of 10.4 [8.6, 12.2] mL) when the circuit was expanded after the preuse self-test (preintervention) and 7% greater (difference of 2.5 [0.7, 4.2] mL) in subjects when the circuit was expanded prior to the preuse self-test (postintervention) (P<.0001). Clinical practice was changed following an intervention of departmental education: the preuse self-test was performed on expanded circuit tubing 11% of the time prior to the intervention and 100% following the intervention. CONCLUSION: Performing a preuse self-test on a nonexpanded pediatric circuit that is then expanded leads to falsely elevated displayed tidal volume in infants less than 10 kg during pressure-controlled ventilation. Overestimation of reported tidal volume can be avoided by expanding the breathing circuit tubing to the length which will be used during a case prior to performing the anesthesia machine preuse self-test. After department-wide education and implementation, performing a correct preuse self-test is now the standard practice in our cardiac operating rooms.

The phenylephrine concentration-response relationship for blood pressure after nasal delivery in children.

BACKGROUND: Intranasal phenylephrine is commonly used to vasoconstrict the nasal mucosa, reducing bleeding associated with nasotracheal intubation or endoscopic sinus surgery. There are few data quantifying either absorption pharmacokinetics or phenylephrine concentration effect on blood pressure in children. METHODS: Published observations of plasma concentration and blood pressure changes after phenylephrine nasal administration (0.1 mL kg-1 , 0.25% or 0.5%) in children (n = 52, 2-12 years, 10-40 kg) were pooled with those in adults (23-81 years) given phenylephrine 2.5% (n = 10) and 10% (n = 10) eyedrops. Further pharmacokinetic (PK) data were available from healthy volunteers given oral phenylephrine 10 mg alone, with blood for concentration assay taken at 5, 15, 30, 45 minutes and 1, 2, 3, 6 hours (n = 28). Intravenous time-concentration data were available from four healthy volunteers given phenylephrine 1 mg and who had blood taken for assay on 17 occasions over the subsequent 4 hours. Data were analyzed using an integrated pharmacokinetic-pharmacodynamic (PK-PD) model using nonlinear mixed-effects models. Allometry, scaled to a 70-kg person, was used for PK size standardization. Effect was described using an EMAX model. RESULTS: A two-compartment model was used to fit PK data while an additional compartment, linked by an equilibration half-time (T1/2 keo), was used to describe effect. PK parameter estimates for the nasal formulation were clearance (CL) 160 L h-1 , central volume of distribution (V1) 13.3 L, intercompartment clearance (Q) 25.3 L h-1 , peripheral volume of distribution (V2) 225 L, absorption half-time (Tabs) 6.2 minutes, absorption lag time (Tlag) 1.5 minutes, and bioavailability (F) 0.183. Bioavailability and absorption of the ophthalmic solution were concentration dependent (F 0.13, Tabs 5.5 minutes for 2.5% solution; F 0.15, Tabs 9.6 minutes for 10% solution). Absorption of the oral formulation was slow (Tabs 48 minutes) with poor bioavailability (F 0.0128). The pediatric PD interrogation revealed a baseline mean arterial pressure of 60 mm Hg, a maximum effect (EMAX ) of 25 mm Hg, and an EC50 of 10.3 µg L-1 . The effect on vasculature was immediate and T1/2 keo was not estimable. CONCLUSION: Absorption of phenylephrine through the nasal mucosa was rapid and similar to the ophthalmic formulation. Bioavailability was also similar to the ophthalmic formulation. The maximum effect (EMAX ) in children was half that in adults (EMAX 50 mm Hg).

Hemodynamic responses and plasma phenylephrine concentrations associated with intranasal phenylephrine in children.

INTRODUCTION: Intranasal phenylephrine, an alpha-1 adrenergic agonist, causes vasoconstriction of the nasal mucosa and is used to reduce bleeding associated with nasotracheal intubation or endoscopic sinus surgery. The purpose of this study was to describe the hemodynamic effects associated with plasma phenylephrine concentrations following topical intranasal administration of 0.25% and 0.5% phenylephrine in children. METHODS: After Institutional Review Board and parental approval, 77 children between the ages of 2 and 12 years were studied in a prospective, double-blind manner and randomized into three groups. Group 1 received intranasal saline, while groups 2 and 3 received 0.1 mL/kg of 0.25% or 0.5% phenylephrine, respectively. All received the same anesthetic of halothane, N2 O, O2 , and vecuronium. After inhalation induction, endtidal halothane and PaCO2 were maintained at 1.5% and 35 mm Hg, respectively. Heart rate and rhythm, systolic, diastolic, and mean, noninvasive arterial blood pressures were recorded and venous blood was obtained for measurement of plasma phenylephrine concentration by high-performance liquid chromatography at baseline and at 2, 5, 10, and 20 minutes following intranasal spray application of the study drug. Nasotracheal intubation was performed immediately following the 5-minute measurements, and the presence of bleeding was assessed. Hemodynamic data were compared by analysis of variance for repeated measures. Bleeding and arrhythmia incidence among groups were analyzed using chi-squared tests. Phenylephrine levels were correlated with hemodynamic values via regression analysis. RESULTS: Fifty-two patients received intranasal phenylephrine. Increases in blood pressure correlated with increasing plasma phenylephrine concentration. Systolic blood pressure increased 8%, and mean blood pressure increased 14%, which were statistically significant but clinically insignificant. Heart rate did not change, and the incidence of arrhythmia was low and similar among groups. Bleeding following nasotracheal intubation was less frequent in Group 3 (11/27 subjects) than in Group 1 (17/25). Peak plasma phenylephrine concentrations were observed by 14±7 minutes following intranasal administration, and were highly variable among individuals (37.8±39.7 and 49.6±93.9 ng/mL [mean±SD] in Groups 2 and 3). DISCUSSION: Administration of intranasal phenylephrine, 0.25% and 0.50%, results in rapid but highly variable systemic absorption that is associated with mild increases of blood pressure that are clinically insignificant. Bleeding associated with nasotracheal intubation was less following administration of 0.5% intranasal phenylephrine than following intranasal saline.

Relating influenza virus membrane fusion kinetics to stoichiometry of neutralizing antibodies at the single-particle level.

The ability of antibodies binding the influenza hemagglutinin (HA) protein to neutralize viral infectivity is of key importance in the design of next-generation vaccines and for prophylactic and therapeutic use. The two antibodies CR6261 and CR8020 have recently been shown to efficiently neutralize influenza A infection by binding to and inhibiting the influenza A HA protein that is responsible for membrane fusion in the early steps of viral infection. Here, we use single-particle fluorescence microscopy to correlate the number of antibodies or antibody fragments (Fab) bound to an individual virion with the capacity of the same virus particle to undergo membrane fusion. To this end, individual, infectious virus particles bound by fluorescently labeled antibodies/Fab are visualized as they fuse to a planar, supported lipid bilayer. The fluorescence intensity arising from the virus-bound antibodies/Fab is used to determine the number of molecules attached to viral HA while a fluorescent marker in the viral membrane is used to simultaneously obtain kinetic information on the fusion process. We experimentally determine that the stoichiometry required for fusion inhibition by both antibody and Fab leaves large numbers of unbound HA epitopes on the viral surface. Kinetic measurements of the fusion process reveal that those few particles capable of fusion at high antibody/Fab coverage display significantly slower hemifusion kinetics. Overall, our results support a membrane fusion mechanism requiring the stochastic, coordinated action of multiple HA trimers and a model of fusion inhibition by stem-binding antibodies through disruption of this coordinated action.

A common solution to group 2 influenza virus neutralization.

The discovery and characterization of broadly neutralizing antibodies (bnAbs) against influenza viruses have raised hopes for the development of monoclonal antibody (mAb)-based immunotherapy and the design of universal influenza vaccines. Only one human bnAb (CR8020) specifically recognizing group 2 influenza A viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (HA) stem and has neutralizing activity against H3, H7, and H10 viruses. Here, we report a second group 2 bnAb, CR8043, which was derived from a different germ-line gene encoding a highly divergent amino acid sequence. CR8043 has in vitro neutralizing activity against H3 and H10 viruses and protects mice against challenge with a lethal dose of H3N2 and H7N7 viruses. The crystal structure and EM reconstructions of the CR8043-H3 HA complex revealed that CR8043 binds to a site similar to the CR8020 epitope but uses an alternative angle of approach and a distinct set of interactions. The identification of another antibody against the group 2 stem epitope suggests that this conserved site of vulnerability has great potential for design of therapeutics and vaccines.

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

OBJECTIVES: Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. DESIGN: Prospective single center observational study. SETTING: Pediatric cardiac ICU. PATIENTS: Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. CONCLUSIONS: In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real-time evaluation of renal near-infrared spectroscopy using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

Landmark papers in pediatric cardiac anesthesia: documenting the history of the specialty.

Pediatric cardiac anesthesia has developed over the past eight decades into a specialty delivering complex clinical care and contributing remarkable scientific progress. The history of this development can be traced through journal articles that mark the strides of the specialty. This article discusses journal articles, chosen by the author, that he considers had a significant impact on the practice of pediatric cardiac anesthesia or are of historical interest.

Remifentanil and propofol undergo separation and layering when mixed in the same syringe for total intravenous anesthesia.

BACKGROUND: Propofol and remifentanil can be combined to deliver total intravenous anesthesia (TIVA). Propofol and remifentanil are sometimes mixed in the same syringe. Since remifentanil is a solution and propofol is an emulsion, we hypothesized that they would separate over time when mixed in the same syringe. METHODS: Nine 60-ml polypropylene syringes were prepared as follows: Group A: 1.25 ml of remifentanil solution (1 mg·ml(-1) ) was added to 48.75 ml of propofol (10 mg·ml(-1) ) in three syringes. Group B: 2.5 ml of remifentanil (1 mg·ml(-1) ) was added to 47.5 ml of propofol (10 mg·ml(-1) ) in three syringes. Group C: 5 ml of remifentanil (1 mg·ml(-1) ) was added to 45 ml of propofol (10 mg·ml(-1) ) in three syringes. The remifentanil lyophilized powder was reconstituted with sterile water and added to the propofol by injection through the port on the bottom of the syringe. The syringe was then inverted five times in succession to mix the drugs. The syringes were mounted in an upright vertical position (plunger on top, port on bottom) with wire on a pegboard. Samples of the mixture were taken from the bottom port (via a 3-way stopcock) and from the top of the syringe (via a stopcock on an 18-gauge needle placed 5 mm through the plunger) at the following time intervals (min) from baseline: T0, T10, T30, T60, T120, T180, T240, T300. Remifentanil and propofol were quantified using specific and validated HPLC/MS/MS assays with automated online sample preparation. RESULTS: Concentrations of remifentanil were significantly greater at the top than the bottom of the syringes in groups A and B. Concentrations of propofol were significantly greater at the bottom than the top of the syringes in all groups. CONCLUSION: Our data indicate that remifentanil solution and propofol emulsion are immiscible: remifentanil separates from propofol and rises to the top. Thus, concentrations of remifentanil and propofol delivered to patients from the same syringe during TIVA are not those expected and cannot be reliable. Remifentanil and propofol should be administered in separate syringes when used in combination for TIVA.

Hemodynamic response to ketamine in children with pulmonary hypertension.

BACKGROUND: The safety of ketamine in children with pulmonary hypertension has been debated because of conflicting results of prior studies in which changes in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) have been widely variable. The goal of this prospective study was to quantitate the effects of ketamine on pulmonary hemodynamics in a cohort of children with pulmonary hypertension under conditions in which variables such as airway/ventilatory management, FiO(2), and use of vasodilating anesthetics were controlled. METHODS: The IRB approved this study of 34 children undergoing cardiac catheterization for pulmonary hypertension studies. Following anesthetic induction with sevoflurane and tracheal intubation facilitated by the administration of rocuronium 0.7-1 mg·kg(-1) iv, sevoflurane was discontinued and anesthesia was maintained with midazolam 0.1 mg·kg(-1) iv (or 0.5 mg·kg(-1) po preoperatively) and remifentanil iv infusion 0.5-0.7 mcg·kg(-1) ·min(-1). Ventilation was mechanically controlled to maintain PaCO(2) 35-40 mmHg. When endtidal sevoflurane was 0% and FiO(2) was 0.21, baseline heart rate (HR), mean arterial pressure (MAP), mPAP, right atrial pressure (RAP), pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic pressure (RVEDP), cardiac output, and arterial blood gases were measured, and indexed systemic vascular resistance (SVRI), indexed pulmonary vascular resistance (PVRI), and cardiac index (CI) were calculated. Each child then received a bolus of ketamine 2 mg·kg(-1) infused over 2 min. Measurements and calculations were repeated 2 min after the conclusion of the infusion. RESULTS: The mean (95% CI) increase in mPAP following ketamine was 2 mmHg (0.2, 3.7), which was statistically significant but clinically insignificant. PVRI and PVRI/SVRI did not change significantly. Hemodynamic changes did not differ among subjects with differing severity of pulmonary hypertension or between subjects chronically treated with pulmonary vasodilators or not. CONCLUSION: Ketamine is associated with minimal, clinically insignificant hemodynamic changes in sedated, mechanically ventilated children with pulmonary hypertension.

Herbert Rackow and Ernest Salanitre: the emergence of pediatric anesthesia as a specialty in the United States.

Herbert Rackow and Ernest Salanitre were pediatric anesthesiologists at Babies Hospital at the Columbia-Presbyterian Medical Center in New York whose work spanned three decades beginning in the early 1950s. Their pioneering research included studies of the uptake and elimination of inhalational anesthetics and of the risk of cardiac arrest in infants and children. They were actively involved in the development of pediatric anesthesia as a specialty, and their efforts contributed to inter-disciplinary collaboration and to the formation of the Section on Anesthesiology of the American Academy of Pediatrics. Their 1969 review article, 'Modern Concepts in Pediatric Anesthesiology', provides a fascinating view of pediatric anesthesia 50 years ago. In 1990, they were jointly awarded the Robert M. Smith award by the Section on Anesthesiology of the American Academy of Pediatrics.

The hemodynamic response to dexmedetomidine loading dose in children with and without pulmonary hypertension.

BACKGROUND: Dexmedetomidine, an α-2 receptor agonist, is widely used in children with cardiac disease. Significant hemodynamic responses, including systemic and pulmonary vasoconstriction, have been reported after dexmedetomidine administration. Our primary goal of this prospective, observational study was to quantify the effects of dexmedetomidine initial loading doses on mean pulmonary artery pressure (PAP) in children with and without pulmonary hypertension. METHODS: Subjects were children undergoing cardiac catheterization for either routine surveillance after cardiac transplantation (n = 21) or pulmonary hypertension studies (n = 21). After anesthetic induction with sevoflurane and tracheal intubation, sevoflurane was discontinued and anesthesia was maintained with midazolam 0.1 mg/kg i.v. (or 0.5 mg/kg orally preoperatively) and remifentanil i.v. infusion 0.5 to 0.8 µg/kg/min. Ventilation was mechanically controlled to maintain PCO2 35 to 40 mm Hg. When end-tidal sevoflurane was 0% and fraction of inspired oxygen (FIO2) was 0.21, baseline heart rate, mean arterial blood pressure, PAP, right atrial pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic pressure, cardiac output, and arterial blood gases were measured, and indexed systemic vascular resistance, indexed pulmonary vascular resistance, and cardiac index were calculated. Each subject then received a 10-minute infusion of dexmedetomidine of 1 µg/kg, 0.75 µg/kg, or 0.5 µg/kg. Measurements and calculations were repeated at the conclusion of the infusion. RESULTS: Most hemodynamic responses were similar in children with and without pulmonary hypertension. Heart rate decreased significantly, and mean arterial blood pressure and indexed systemic vascular resistance increased significantly. Cardiac index did not change. A small, statistically significant increase in PAP was observed in transplant patients but not in subjects with pulmonary hypertension. Changes in indexed pulmonary vascular resistance were not significant. CONCLUSION: Dexmedetomidine initial loading doses were associated with significant systemic vasoconstriction and hypertension, but a similar response was not observed in the pulmonary vasculature, even in children with pulmonary hypertension. Dexmedetomidine does not appear to be contraindicated in children with pulmonary hypertension.

Acute pulmonary vasodilator testing with inhaled treprostinil in children with pulmonary arterial hypertension.

Acute pulmonary vasodilator testing (AVT) is essential to determining the initial therapy for children with pulmonary arterial hypertension (PAH). This study aimed to report the initial experience with inhaled treprostinil used for AVT in children with PAH and to evaluate the hemodynamic change after inhaled treprostinil compared with inhaled nitric oxide. This prospective cohort study was designed for 13 children who underwent AVT with inhaled treprostinil or oxygen plus inhaled nitric oxide (iNO) during catheterization. Inhaled treprostinil was delivered during cardiac catheterization by adapting the Optineb ultrasonic nebulizer via either a flow-inflating bag or the manual mode of the anesthesia system. The median age of the patients was 10 years (range 4-17 years). The etiologies of PAH included idiopathic PAH and associated PAH. All the patients tolerated inhaled treprostinil without marked clinical worsening and received six or nine breaths (36 or 54 µg) of treprostinil. The median of the total treprostinil doses was 1.53 µg/kg (range 0.71-2.89 µg/kg). Inhaled treprostinil was administrated via an endotracheal tube (n = 8), anesthesia mask (n = 3), or laryngeal mask airway (n = 2). Inhaled nitric oxide (iNO) and inhaled treprostinil significantly decreased the mean pulmonary artery pressure and the pulmonary vascular resistance index compared with baseline. Three adverse events were reported after inhaled treprostinil, including cough and mild to moderate hypotension with higher doses. All adverse events resolved without any intervention. This study report is the first to describe the use of inhaled treprostinil for AVT in children with PAH. In this small pediatric cohort, inhaled treprostinil was effectively delivered and well tolerated and may be useful for AVT.

Femoral artery catheterization in neonates and infants.

OBJECTIVE: To determine the incidence of perfusion-related complications associated with indwelling femoral artery monitoring catheters in neonates and infants following introduction of a 2.5-F diameter, 5-cm length, polyethylene catheter (Cook Medical, Bloomington, IN) to our unit. DESIGN: Prospective observational cohort study. SETTING: Pediatric cardiac intensive care unit in a university-affiliated children's hospital. PATIENTS: All patients <2 yrs old with an indwelling femoral artery catheter during a 3-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred eighty-two patients (including 98 neonates), median (range) age 10 wks (0.1-84), weight 4.1 kg (2.0-11.1) were enrolled; outcomes in 249 were evaluable. Pulse strength in dorsalis pedis arteries and pulse discrepancies between feet were assessed hourly by the cardiac intensive care unit nurse and recorded on a flow sheet. Nonpalpable pulses were assessed as "absent" or "present" with ultrasonic Doppler. Following removal of the catheter, assessments of pulse strength continued until resolution of any discrepancies. Median (range) duration of catheterization was 4 days (1-23). Catheters of 2.5-F diameter were used in 227 patients and larger catheters in 55 patients. The incidence of pulse strength discrepancies between feet was 20%, loss of pulse was 3.4% (6.7% in neonates, 1.4% in older infants) when extracorporeal membrane oxygenation patients were excluded, and resolution of pulse discrepancy or loss was 100%. Duration of catheterization and use of a catheter larger than 2.5 Fr were significant predictors of loss of pulse. CONCLUSIONS: Loss of pedal pulse distal to small-bore monitoring femoral artery catheters in neonates and infants is directly related to the duration of catheterization and is less frequent when 2.5-F, 5-cm polyethylene catheters are used instead of larger catheters.

Screening by pulse CO-oximetry for environmental tobacco smoke exposure in preanesthetic children.

OBJECTIVE: The purpose of this study was to evaluate the ability of multiple wavelength pulse CO-oximetry (SpCO) to screen for environmental tobacco smoke (ETS) exposure in children. BACKGROUND: Exposure to ETS is associated with an increased risk of perioperative respiratory complications in children. It is often difficult to obtain an accurate history for ETS exposure, so a preoperative screening tool is desirable. Carbon monoxide is a measurable product of tobacco combustion. Multiple wavelength pulse CO-oximetry is a recently developed point-of-care monitor. METHODS: Following IRB approval and parental consent, 220 children aged 1-16 years having outpatient surgical procedures were enrolled. SpCO was measured preoperatively three times with the Radical-7 Rainbow SET CO-oximeter (Masimo, Irvine, CA, USA). Immediately following induction of anesthesia, a blood sample for laboratory measurement of carboxyhemoglobin (COHb) and serum cotinine was obtained. Regression analysis determined the correlation of SpCO with serum cotinine values. Receiver operator characteristic (ROC) curves analyzed the discriminating ability of SpCO or COHb to predict ETS exposure based on cotinine cutoff values known to be present in children exposed to ETS. Agreement of SpCO and COHb values was assessed using Bland-Altman plots. RESULTS: SpCO did not correlate with cotinine (R(2) = 0.005). Both SpCO and COHb had poor discriminating ability for ETS exposure (area under the ROC curve = 0.606 and 0.562, respectively). SpCO values had poor agreement with COHb values. CONCLUSIONS: The point-of-care multiple wavelength pulse CO-oximeter does not appear to be a useful preoperative screening tool for ETS exposure in children.