John F. Ryan

A Controlled Trial of a Formalin-Inactivated Hepatitis A Vaccine in Healthy Children

BACKGROUND Although inactivated hepatitis A vaccine is known to be well tolerated and immunogenic in healthy children and adults, its efficacy has yet to be established. METHODS To evaluate the efficacy of the hepatitis A vaccine in protecting against clinically apparent disease, we conducted a double-blind, placebo-controlled trial in an Hasidic Jewish community in upstate New York that has had recurrent outbreaks of hepatitis A. At the beginning of a summer outbreak, 1037 healthy seronegative children 2 to 16 years of age were randomly assigned to receive one intramuscular injection of a highly purified, formalin-inactivated hepatitis A vaccine or placebo. A case was defined by the presence of typical signs and symptoms, a diagnostic increase in IgM antibody to hepatitis A, and a serum concentration of alanine aminotransferase at least twice the upper limit of normal. Cases occurring greater than or equal to 50 days after the injection were included in the evaluation of efficacy. The children were followed for a mean of 103 days. RESULTS A total of 519 children received vaccine, and 518 received placebo. The vaccine was well tolerated, with no serious adverse reactions. From day 50 after the injection, 25 cases of clinically apparent hepatitis A occurred in the placebo group and none in the vaccine group (P less than 0.001), confirming that the vaccine had 100 percent protective efficacy. Before day 21, seven cases occurred in the vaccine group and three cases in the placebo group. After that time, there were no cases among vaccine recipients and 34 cases among placebo recipients. CONCLUSIONS The inactivated purified hepatitis A vaccine that we tested is well tolerated, and a single dose is highly protective against clinically apparent hepatitis A.

A Single-blind Study of Pulse Oximetry in Children

Oxygen saturation determined by pulse oximetry was monitored in 152 pediatric surgical patients divided into two groups. In one group, the oximeter data and alarms were available (N = 76) to the anesthesia team, and, in the other group, these data were unavailable (N = 76). A trained observer recorded all intraoperative hypoxic episodes and informed the anesthesia team of all major events (i.e., oxygen saturation less than or equal to 85% for greater than or equal to 30 s) (PaO2 approximately 52 mmHg). Thirty-five major events occurred: 24 in the unavailable group, and 11 in the available group (P = 0.021). A greater number of major events occurred in children less than or equal to 2 yr of age (P = 0.013). Hypoxic events diagnosed by the oximeter, but not by the anesthesiologist, were more frequent in the unavailable group (13) than in the available group (5) (P = 0.0495). ASA Physical Status 3 and 4 patients were more likely to suffer a major event (P = 0.009 available, 0.006 unavailable). The pulse oximeter diagnosed hypoxemia before the signs and symptoms of hypoxemia were apparent (i.e., prior to observed cyanosis or bradycardia). Major hypoxic events were unrelated to duration of anesthesia. Major events were evenly distributed among induction, maintenance, and awakening from anesthesia; a greater number of hypoxic events occurred during induction in the unavailable group (P = 0.031). No morbidity was documented in any patient who suffered an hypoxic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Life-threatening Apnea in Infants Recovering from Anesthesia

To determine whether prematurely born infants with a history of idiopathic apneic episodes are more prone than other infants to life-threatening apnea during recovery from anesthesia, the authors prospectively studied 214 infants (173 full term, 41 premature) who received anesthesia. Fifteen premature infants had a preanesthetic history of idiopathic apnea. Six of these required mechanical ventilation because of idiopathic apneic episodes during emergence from anesthesia. Two were ventilated for other reasons, and seven recovered normally. Infants ventilated for apnea were younger (postnatal age 1.6 +/- 1.2 months, mean +/- SD; conceptual age 38.6 +/- 3.0 weeks) than those who recovered normally (postnatal age 5.6 +/- 2.7 months; conceptual age 55.1 +/- 11.3 weeks) (P less than 0.01). No other premature or full-term infant was ventilated because of postoperative apneic episodes. The authors conclude that anesthetics may unmask a defect in ventilatory control of prematurely born infants younger than 41-46 weeks conceptual age who have a preanesthetic history of idiopathic apnea.

Kinetic studies of Ca2+ release from sarcoplasmic reticulum of normal and malignant hyperthermia susceptible pig muscles.

The time-course of Ca2+ release from sarcoplasmic reticulum isolated from muscles of normal pigs and those of pigs susceptible to malignant hyperthermia were investigated using stopped-flow spectrophotometry and arsenazo III as a Ca2+ indicator. Several methods were used to trigger Ca2+ release: (a) addition of halothane (e.g., 0.2 mM); (b) an increase of extravesicular Ca2+ concentration ([Ca2+0]); (c) a combination of (a) and (b), and (d) replacement of ions (potassium gluconate with choline chloride) to produce membrane depolarization. The initial rates of Ca2+ release induced by either halothane or Ca2+ alone, or both, are at least 70% higher in malignant hyperthermic sarcoplasmic reticulum than in normal. The amount of Ca2+ released by halothane at low [Ca2+0] in malignant hyperthermic sarcoplasmic reticulum is about twice as large as in normal sarcoplasmic reticulum. Membrane depolarization led to biphasic Ca2+ release in both malignant hyperthermic and normal sarcoplasmic reticulum, the rate constant of the rapid phase of Ca2+ release induced by membrane depolarization being significantly higher in malignant hyperthermic sarcoplasmic reticulum (k = 83 s-1) than in normal (k = 37 s-1). Thus, all types of Ca2+ release investigated (a, b, c and d) have higher rates in malignant hyperthermic sarcoplasmic reticulum than normal sarcoplasmic reticulum. These results suggest that the putative Ca2+ release channels located in the sarcoplasmic reticulum are altered in malignant hyperthermic sarcoplasmic reticulum.

Percutaneous catheterization of the radial artery in the critically ill neonate.

Percutaneous catheterization of the radial artery appears to be a simple and safe alternative to catheterization of the umbilical artery for monitoring critically ill neonates. This avoids the serious and potentially fatal complications associated with use of the umbilical arterial catheter, and it is also applicable to monitoring of neonates in whom the umbilical artery is no longer patent. We observed no serious sequelae in cannulation of the radial artery and think that the technique should be used more widely.

Myoglobinemia after a single dose of succinylcholine.

Abstract The frequency of myoglobinemia after a single intravenous dose of succinylcholine was determined in 40 children and 30 adults. Myoglobin was measured in serial serum samples by a specific immune precipitin technic sensitive to 5 μg per milliliter. Myoglobinemia developed in one adult and 16 children after the intravenous administration of succinylcholine but not, in 12 children, after intramuscular injection. These findings point to a difference in muscle responsiveness in children to this depolarizing muscle relaxant. This response diminishes with the onset of puberty. The development of myoglobinemia after the administration of succinylcholine, although it did not appear to affect recovery from surgery, accentuates the need for another type of short-acting muscle relaxant for use in children.

Re-evaluation of dosage and duration of action of d-tubocurarine in the pediatric age group.

A cumulative dose-response curve for d-tubocurarine based on body weight was determined for 44 infants and children 1 day to 7 years of age during halothane, nitrous oxide and oxygen anesthesia. Depression of thumb adduction was measured. Age difference did not affect the mean dose-effect response. Infants less than 10 days old, however, showed the widest deviation of responses. When the effect of d-tubocurarine is determined by twitch response, infants and children are more resistant to d-tubocurarine and recover faster than adults from similar levels of neuromuscular depression. Monitoring of neuromuscular function by train-of-four stimulation proved as useful as it is in adults.

Wasted Ventilation Measured In Vitro with Eight Anesthetic Circuits with and without Inline Humidification

Compression of gases (Boyles law) and circuit compliance are major determinants of anesthesia circuit function. The materials of which circuits are constructed and the use of heated humidifiers may result in clinically important variations in delivered minute ventilation (VE) secondary to variations in compression volume. We examined eight anesthetic circuits both with and without a heated humidifier in an in vitro setting. Compression volume was determined with a large calibrated syringe. Circuit efficiency was determined by measuring VE at multiple peak inflation pressures (PIP) while using a pediatric ventilator with fixed VE, respiratory rate, fresh gas flow, and I/E ratio. As expected, both compression volume and delivered VE highly correlated with the type of circuit and the pressure at which it was examined (P less than 0.001). Mapleson D circuits had the lowest compression volume and were the most efficient circuits (P less than 0.0001). Pediatric circle systems were intermediate and adult circle systems had the largest compression volume and were the least efficient. Humidifiers uniformly increased compression volume. The following conclusions were drawn: 1) the anesthetic circuit, its material, and the pressure at which it operates are important determinants of circuit function; 2) humidifiers increase compression volume; 3) Mapleson D circuits had the lowest compression volume and therefore were the most efficient; 4) highly compliant adult circuits may result in compression volume losses that exceed the tidal volume of a pediatric ventilator; 5) humidifiers with low volume and rigid tubing should have the least effect on minute ventilation; and 6) highly compliant adult circuits when used in the care of infants and small children must be used with caution.

Sudden unexplained death in a patient with a family history of malignant hyperthermia

A 23-year-old healthy white male in excellent physical condition developed cardiac arrest and rigidity during moderate exercise. He had a strong family history of malignant hyperthermia (MH). Two hours postmortem, his temperature was noted to be markedly elevated [41 degrees C (106 degrees F)]. A review of the possible differential diagnoses point to MH as a reasonable etiology.

Dantrolene prevents the malignant hyperthermic syndrome by reducing free intracellular calcium concentration in skeletal muscle of susceptible swine.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle triggered when susceptible subjects are exposed to volatile anesthetic agents and/or depolarizing muscle relaxants. We have used Ca2+ selective microelectrodes to measure in vivo the intracellular free [Ca2+] in skeletal muscle of MH susceptible swine before and after the administration of dantrolene. We have investigated the effectiveness of this muscle relaxant in preventing clinical MH and the relationship between the resting intracellular free [Ca2+] and the probability of inducing the MH syndrome. The resting intracellular free [Ca2+] was 0.41 +/- 0.01 microM (M +/- SEM), which agrees with our previous measurements in susceptible swine. The administration of 0.5, 1, 2, 2.5 and 3 mg/Kg Dantrolene, reduced the intracellular free [Ca2+] to 0.31, 0.21, 0.09, 0.08, 0.08 microM respectively. The 0.5 mg/Kg dose induced a moderate decrease of [Ca2+]i and failed to prevent the MH syndrome after exposure to halothane (2%). The 1 mg/Kg dose produced a further reduction in [Ca2+]i and was sufficient to prevent the clinical syndrome in 2 out of 3 animals. The 2.5 mg/Kg dose was uniformly protective in all animals. These results suggest that the mechanism by which dantrolene protects susceptible animals exposed to triggering agents is by reducing the intracellular free [Ca2+] in skeletal muscle.