James K. Alifimoff

Induction and maintenance characteristics of anesthesia with desflurane and nitrous oxide in infants and children.

To determine the induction and maintenance characteristics of desflurane in pediatric patients, the authors anesthetized 206 infants and children aged 1 month to 12 yr with nitrous oxide plus desflurane and/or halothane in oxygen. Patients were assigned to one of four groups: anesthesia was 1) induced and maintained with desflurane after premedication with an oral combination of meperidine, diazepam, and atropine; 2) induced and maintained with desflurane; 3) induced with halothane and maintained with desflurane; or 4) induced and maintained with halothane. An unblinded observer recorded time to loss of consciousness (lid reflex), time to intubation, and clinical characteristics of the induction and maintenance of anesthesia. Moderate-to-severe laryngospasm (49%) and moderate-to-severe coughing (58%) occurred frequently during induction of anesthesia with desflurane; the incidence of these was not altered by premedication. In contrast, laryngospasm and coughing were rare during induction of anesthesia with halothane. In unpremedicated patients, time to loss of lid reflex (mean +/- SD) was similar for desflurane (2.4 +/- 1.2 min) and halothane (2.1 +/- 0.8 min). During induction of anesthesia, before laryngoscopy and intubation, mean arterial pressure less than 80% of baseline was more common with halothane; heart rate and mean arterial pressure greater than 120% of baseline were more common with desflurane. Intraoperatively, heart rate greater than 120% of baseline was more common with desflurane; blood pressures were similar for the two anesthetics. The authors conclude that the high incidence of airway complications during induction of anesthesia with desflurane limits its utility for inhalation induction in pediatric patients. Anesthesia can be safely maintained with desflurane if induced with a different anesthetic.

Anaesthetic potencies of primary alkanols: implications for the molecular dimensions of the anaesthetic site.

1 We have redetermined the anaesthetic potencies (EC50s) for a series of primary alkanols, to resolve uncertainties about the molecular dimensions of the anaesthetic site resulting from the use of data from different laboratories. 2 For each alkanol, concentration‐response relationships for loss of righting reflex (LRR) were plotted for over one hundred tadpoles, and the median effective concentrations determined. Aqueous concentrations present during potency assays were determined independently, and for alkanols with chain length greater than nonanol, correction was made for depletion from the aqueous phase. 3 The EC50 s were found to decrease logarithmically with increasing number of carbon atoms in the hydrocarbon chain of the alkanol (CN), such that, on average, each additional methylene group was associated with an approximately four fold increase in potency. 4 The relationship between log EC50 and CN was best described by the quadratic equation, log EC50 = 0.022 (±0.0038) CN2 + 0.76 (±0.051) CN + 3.7 (±0.14) (r2 = 0.9951). 5 A previously described correlation between the apparent changes in the free energy of binding of an additional methylene group both to luciferase and to the sites for LRR in tadpoles was not confirmed. 6 A cut‐off in potency beyond dodecanol was established in experiments where tadpoles were maintained in supersaturated solutions of tridecanol for 20 h without demonstrable LRR. 7 These findings indicate that the soluble enzyme firefly luciferase does not adequately model the anaesthetic site. Specifically, there are discrepancies in the position of cut‐off, and the apparent changes in the free energy of binding, per methylene group, of an alkanol to luciferase do not parallel that for tadpoles.

Neuromuscular and cardiovascular effects of mivacurium in children.

The neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) were evaluated in 90 children (2-12 yr) during N2O:O2 halothane or N2O:O2 narcotic anesthesia. Neuromuscular response was evaluated by recording the force of contraction of the adductor of the thumb during train-of-four stimulation at 0.1 Hz. The children were divided into two groups. Patients in group A (n = 45) were anesthetized with N2O:O2 and halothane (1% inspired) and patients in group B (n = 45) were anesthetized with N2O:O2 and fentanyl or morphine. Each group was further divided into five subgroups of nine children. Children in the first three sets of subgroups (A1-A3, B1-B3) received an initial dose of 0.02, 0.04, 0.05, 0.06 or 0.07 mg/kg mivacurium to determine dose response relationships under the different anesthetic regimens. The ED50 and ED95 neuromuscular blocking doses calculated from this single dose technique were 0.051 mg/kg and 0.095 mg/kg, respectively, in children anesthetized with halothane N2O:O2, and 0.059 mg/kg and 0.11 mg/kg in children anesthetized with N2O:O2 narcotic. The fourth subset of each group (A4 and B4) received 0.09 mg/kg and 0.11 mg/kg mivacurium, the estimated ED95 for each respectively. The last subsets (A5 and B5) received 0.2 mg/kg. This dose induced 100% depression of the twitch response in all 18 patients in 1.8 +/- 0.1 min, with recovery to 5%, 25%, and 95% of control occurring in 8.4 +/- 0.5, 11.2 +/- 0.6 and 18.4 +/- 1.6 min, respectively. The recovery indices for all patients were 4.6 +/- 0.6 min for 25-75% recovery and 9.7 +/- 1.3 min for 5-95% recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of open-chest cardiac massage techniques in dogs

Manual compression of the heart during open-chest cardiac massage (OCPR) has been shown to be superior to closed-chest compression. Our study sought to determine, in a canine model, the optimal hand position for manual compression of the heart. Twelve dogs were anesthetized with ketamine, an orotracheal tube was placed, and anesthesia was maintained with halothane and nitrous oxide. Cannulae were placed to monitor diastolic (DBP) and systolic (SBP) blood pressures, intracranial pressure (ICP), and common carotid blood flow (CCBF). Control values were obtained under light general anesthesia, and ventricular fibrillation was induced. External CPR (ECPR) was performed with a mechanical compressor before opening the chest and pericardium through the left fifth interspace. The following sequence of three hand positions was used for OCPR: technique A, one-handed technique with thumb on left ventricle, fingers over the right ventricle, and apex in palm; technique B, two-handed technique with right ventricle cupped in left hand and fingers of right hand over left ventricle; and technique C, one-handed technique with fingers of right hand over left ventricle and heart against sternum. Each was done at a rate of 60 compressions per minute with the operator blind to results during performance. All three techniques produced significantly (P less than .05) greater DBPs and CCBFs when compared with ECPR. All three also produced significantly lower (P less than .05) ICPs when compared with ECPR. DBPs, SBPs, CCBFs, and cerebral perfusion pressures were similar for techniques B and C, and all were significantly greater (P less than .05) than those achieved with technique A.(ABSTRACT TRUNCATED AT 250 WORDS)

Stereoselectivity of Channel Inhibition by Secondary Alkanol Enantiomers at Nicotinic Acetylcholine Receptors

BackgroundAt the nicotinic acetylcholine receptor, long chain alkanols reduce, whereas short chain alkanols augment endplate currents. Using the enantiomers of five members of a homologous series of secondary alkanols (2-butanol through 2-octanol), we tested the hypothesis that these actions occur at a single hydrophobic site in the lumen of the channel. Small alkanols would bind to this site without blocking the channel, stabilizing the open state and enhancing the apparent affinity of the agonist for channel opening. Long chain alkanols would bind the same site and simply inhibit without affecting the agonists apparent affinity. MethodsAgonist-stimulated 86Rb+ efflux from acetylcholine receptor-rich vesicles from Torpedo nobiliana was studied by adding agonist and allowing efflux to proceed for 10 s before termination by filtration. ResultsAll of the 2-alkanols inhibited 86Rb+ efflux elicited by a maximally stimulating concentration of agonist. Inhibitory potency increased logarithmically with the number of carbon atoms in the hydrocarbon chain of the alkanol. The inhibitory potency of the enantiomers of 2-butanol differed twofold, but the other enantiomers exhibited no stereoselectivity. The enantiomers of 2-octanol caused a concentration-dependent depression of carbamylcholine-stimulated 86Rb+ efflux without significantly altering the agonists apparent dissociation constant. In contrast, the enantiomers of 2-butanol caused: (1) a nonstereoselective decrease in carbachols apparent dissociation constant and (2) the expected stereoselective decrease in maximal carbamylcholine-stimulated 86Rb+ efflux. ConclusionsThe alkanol site that modulates the apparent agonist affinity for channel opening is distinct from the site that results in inhibition of cation flux through the channel.

Open versus closed chest cardiac massage in nontraumatic cardiac arrest

Since the rediscovery and popularization of closed-chest cardiopulmonary resuscitation (CPR) in the early 1960s, this technique has largely replaced open-chest cardiac massage. However, in the ensuing quarter of a century, a large amount of data has been accumulated that seems to indicate that open-chest CPR is the physiologically superior method of cardiopulmonary resuscitation. This paper reviews that data comparing these two CPR modalities. The first part discusses data obtained from animal studies, while the second considers the limited amount of information that has been obtained from human investigations. The authors concludes that a randomized clinical trial of open-chest and closed-chest CPR is needed to fully evaluate the efficacy of these two resuscitative techniques as well as to define the most appropriate circumstances for the use of internal cardiac massage.

Enflurane, halothane and isoflurane do not inhibit angiotensin converting enzyme activity.

We studied the effect of halothane, enflurane and isoflurane on angiotensin converting enzyme (ACE) activity using [3H].benzoyl-phenylalanyl-alanyl-proline (BPAP) as a substrate. Isolated rabbit lungs were perfused in a recirculating system in vitro with BPAP in Krebs-Ringer solution. The rate of metabolism and per cent metabolism were determined before and after treatment for 30 minutes with four MAC multiples of enflurane, halothane or isoflurane. The effects of the anaesthetics on ACE activity were determined by calculating per cent inhibition of metabolism of BPAP using data from the control and test period for each lung. The average metabolism of BPAP at 15 minutes during the control period was 76.5 per cent (± 1.92 SEM). No anaesthetic significantly inhibited metabolism of BPAP. Likewise there was no effect on BPAP first order kinetics. Although potent in. halation anaesthetics may alter the renin-angiotensinaldosterone axis, the), do not affect this crucial step.RésuméOn a étud ié l’effet de l’halothane, l’enflurane et l’isoflurune sur l’activité de l’enzyme responsable de la conversion de l’angiotensine (ACE) utilisant le [3H]-benzoyl-phenylalanyl-aianyl-proline (BPAP) comme substrat. Des poumons de lapins isolés ont été perfusés dans un système permettant une recirculation in-vitro avec le BPAP dans une solution de Krebs-Ringer. Le taux et le pourcentage du métabolisme ont été déterminés avant et après traitement pour 30 minutes avec des concentrations attdgnant quotre fois le MAC d’enflurane, d’halothane ou d’isoflurane. Les effets des anesthésiques sur l’activité du ACE ont été déterminés en calculant le pourcentage d’inhibition du métabolisme du BPAP utilisant les données de contrôle ainsi que les données du test pour chaque poumon. Le métabolisme moyen du BPAP à 15 minutes pendant la période de contrô1e a été de 76.5 pour cent (± 1.92 SEM). Aucun des anesthésiques a inhibé d’une façon significative le métabolisme du BPAP. Aussi H n’y avait aucun effet sur la cinétique du premier ordre du BPAP. Même si les agents anesthésiques d’inhalation puissants peuvent altérer l’axe de la rénine-angiotensine-aldostérone, ils n’ affectent pas cette étape cruciale.