Joseph J. Buckley

Pharmacokinetics of fentanyl in neonates

The pharmacokinetics of fentanyl were studied in fourteen neonates undergoing major surgical procedures. Five patients were less than 1 day of age, seven ruere 1–4 days old, and two were 7–14 days old. Fentanyl was given intravenously, 10 μg/kg (n = 1), 25 μg/kg (n = 4), or 50 μg/kg (n = 9), and plasma concentrations measured at intervals of up to 18 hr. Average weight was 2.9 kg. The injection of 25 or 50 μg/kg of fentanyl over 1–3 min was hemodynamically well-tolerated by all patients. Four newborns without respiratory impairment secondary to surgery or disease needed ventilatory support for an average of 24 hr (range 11–40 hr). Plasma concentrations of fentanyl were most appropriately described by a two-compartment model. The mean ± SEM values of selected model parameters were volume of the central compartment, 1.45 ± 0.34 L/kg; volume of distribution at steady state. 5.1 ± 1 L/kg; clearance, 17.94 ± 4.38 ml·kg−1·min−1; and terminal elimination half-life (t1/2,β), 317 ± 70 min. In seven patients transient rebound in plasma fentanyl concentrations of 0.5 ng/ml or greater occurred. In three patients patients with markedly increased intraabdominal pressure, the t1/2β was 1.5–3 times the population mean. Thus fentanyl disposition in neonates is highly variable, but the t1/2β is predictably prolonged in the presence of increased abdominal pressure.

Comparison of indirect and direct methods of measuring arterial blood pressure.

Direct and indirect determinations of blood pressure have been recorded in 70 human subjects. Statistical analysis of the results is presented. A frequent discrepancy between direct and indirect readings is evident with the drift of the latter falling increasingly below the direct measurement as blood pressure rises. The greatest discrepancy is found in the young hypertensive subject and the possible clinical implications of this finding are discussed. An attempt is made to explain some of the factors contributing to the variable error by which auscultatory readings underestimate the true intraarterial pressure.

Children with mucopolysaccharidosis: Perioperative care, morbidity, mortality, and new findings

The perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis (MPS) are presented. They underwent a detailed preoperative assessment and were anesthetized 141 times. An intravenous induction technique was used in most patients. It was easier to see the vocal cords, during laryngoscopy, in children with Hurler syndrome (HS) when they were younger (23 v 41 months, P < or = .01) and smaller (12 v 15 kg, P < or = .05). Preoperative obstructive breathing was associated with a significantly higher incidence of postextubation obstruction (P < or = .05). A total of 28 children underwent bone marrow transplantation (BMT); this reversed upper airway obstruction and also reversed intracranial hypertension. In children with HS, the incidence of odontoid dysplasia was 94%; 38% demonstrated anterior C1-C2 subluxation. Head and neck manipulation was limited in children with cervical spine defects. None of the 30 patients experienced spinal cord morbidity. One child suffered an intraoperative stroke; another, pulmonary edema. Severe and extensive coronary obstruction was responsible for 2 intraoperative deaths. Coronary angiography underestimated coronary artery disease.

Percutaneous cervical central venous line placement: A comparison of the internal and external jugular vein routes

To compare the rate of success and incidence of complications associated with two currently popular routes of percutaneous central venous cannulation, we studied 167 patients in whom either internal or external jugular vein catheterization was attempted. Internal jugular vein (IJV) catheterization (125 patients) was successful in 91 %; an intrathoracic location was achieved in 100%; complications occurred in 12.8%. Complications included one case of catheter malposition, one case of tension pneumothorax, and 12 instances of inadvertent carotid artery puncture, one resulting in a paratracheal hematoma and phrenic nerve compression. The success rate of IJV cannulation was higher and carotid artery puncture less frequent when an 18-gauge thin-walled needle and a straight guide-wire were used than when IJV cannulation was performed by blind puncture with a larger over-the-needle catheter. Delayed vein perforation occurred twice. External jugular vein cannulation (42 patients), using a “J” wire technique, yielded a 76% success rate: 93.7% of catheter tips reached an intrathoracic location. No complications occurred. We conclude that IJV cannulation is a more reliable means of percutaneous central venous line placement but is associated with a significant incidence of complications which can be reduced if a technique employing a scout needle and guide-wire is used.

Accuracy of radial artery blood pressure determination with the Vasotrac

PurposeTo evaluate the accuracy of a new non-invasive method (Vasotrac™) to measure blood pressure (BP) with accompanying arterial wave-form and pulse-rate display when compared with BP and waveform measured invasively.MethodsHealthy volunteers (n=53) served as subjects for the study. Blood pressures and waveforms obtained via a radial artery catheter (IABP) were compared with non-invasive measurements obtained every 12–15 beats by the new system (Vasotrac BP) from the opposite radial artery. In a sub-group of volunteers (n= 11), BP was acutely increased and decreased with isoproterenol, phenylephrine and sodium nitroprusside. Data were analyzed by determining correlation and agreement between the two systems of measurement. Waveforms obtained by the two systems were qualitatively examined.ResultsNon-invasive BP measured every 12–15 beats by the Vasotrac correlated with IABP (systolic r2 = 0.89; diastolic r2 = 0.88; mean r2 = 0.94). The actual values obtained by the two methods agreed closely with > 90% of readings being within 2SDs when plotted by the Bland Altman method. This was also true during vasoactive drug infusion when BP changed acutely and swiftly. During this dynamic period, Vasotrac BP accurately tracked the changes in IABP with correlations (systolic r2= 0.82; diastolic r2 = 0.89; mean r2 = 0.95) and close agreement (> 90% of readings were within 2 SDs in the Bland Altman plot). Waveforms displayed by the two systems were qualitatively very similar. Pulse rates measured by the two systems were identical.ConclusionsThe Vasotrac system displayed an arterial waveform which was similar to that obtained directly and measured BP and pulse rate accurately. It should be a convenient device to measure BP continually in a non-invasive fashion.RésuméObjectifÉvaluer l’exactitude d’une nouvelle méthode non effractive de mesure (Vasotrac™) de la tension artérielle (TA), avec les graphiques qui l’accompagnent montrant les ondes artérielles et les fréquences de pouls, en la comparant avec une méthode effractive et ses graphiques.MéthodeDes volontaires en santé (n = 53) ont participé à l’étude. Les tensions artérielles et les courbes artérielles obtenues au moyen d’un cathéter de l’artère radiale (TAIA) ont été comparées aux mesures non effractives obtenues à tous les 12–15 battements de l’artère radiale opposée avec le nouveau système (TA Vasotrac). Chez des volontaires (n = 11) d’un sous-groupe, on a provoqué une hausse et une baisse soudaines de la TA avec de l’isoprotérénol, de la phényléphrine et du nitroprussiate de sodium. Les données ont été analysées en déterminant la corrélation et la concordance entre les deux systèmes de mesure. On a examiné les caractéristiques des graphiques obtenus des deux systèmes.RésultatsLes mesures non effractives de TA faites tous les 12–15 battements avec le Vasotrac sont en corrélation avec celles du système de TAIA(r2 systolique = 0,89; r2 diastolique = 0,88; moyenne de r2 = 0,94). Les tracés, d’après Bland Altman, des valeurs provenant des deux systèmes concordaient étroitement, indiquant > 90% des mesures qui se situent à l’intérieurs de 2 écarts-types. Il y a eu la même corrélation pendant la perfusion de médicament vasoactif. Pendant cette période dynamique, la TA Vasotrac a suivi avec précision les changements de la TAIA avec des mesures correspondantes (r2 systolique = 0,82; r2 diastolique = 0,89; moyenne de r2 = 0,95) et d’étroites concordances (> 90% à l’intérieur de 2 écarts-types). Les graphiques produits par les deux systèmes étaient qualitativement très similaires. Les fréquences de pouls étaient identiques.ConclusionLe système Vasotrac a permis de visualiser des ondes artérielles similaires à celles qui ont été obtenues directement, et a mesuré la TA et la fréquence de pouls avec précision. C’est un appareil qui peut être pratique pour mesurer continûment la TA d’une manière non effractive.

Prevention of ventricular fibrillation during hypothermia with bretylium tosylate.

ENTRICULAR fibrillation (V.F.) continV ues to be a significant drawback to the use of hypothermia in clinical medicine. More than two decades of extensive investigation have failed to identify the fundamental mechanism(s) responsible for this arrhythmia. Many factors, such as pH and ionic deviations, type of anesthesia, and extrinsic cardiac stimulation, are known to influence the incidence of V.F., but no reliable means has been found to prevent its occurrence.

Adverse drug interaction involving pancuronium and aminophylline.

A 61-year-old, 83-kg, white man was scheduled to undergo lower thoracic posterior spinal fusion -to stabilize a compression fracture of the 12th thoracic vertebra. Before the injury the patient had been in good health. Six months before this admission, the patient had had a renal cyst drained under general anesthesia without complication. At that time, he reported a smoking history of 100 pack years. Pulmonary function tests demonstrated severe obstructive lung disease which responded to bronchodilators. Despite this, preoperative aminophylline was not given before or during that operation. The preoperative electrocardiogram (ECG) obtained during this admission showed that only infrequent premature atrial and ventricular beats and nonspecific ST-T changes. Blood gas tensions were normal. The anesthetic included preoperative diazepam (15 mg), Innovar, and thiopental for induction, followed by pancuronium, 8 mg, to facilitate tracheal intubation. Both surgery and anesthesia were we11 tolerated and no complications ensued. During the present admission, because of his severe chronic obstructive pulmonary disease, the patient was given a loading dose of oral aminophylline (6 mg/kg), followed by 800 mg/day in divided doses for 1 week before surgery. Chest physiotherapy was also carried out. The patient had significant subjective improvement with this therapy. The serum aminophylline level on the 3rd day of treatment was 12.4 pg/ml. Chest roentgenogram was clear and ectopy was not present on an ECG taken the night before surgery. Other laboratory data were within normal limits. O n the morning of surgery, the patient received oral aminophylline (200 mg), and atropine (0.6 mg) and secobarbital (100 mg) intramuscularly. Forty-five minutes later, an ECG taken in the operating room revealed an occasional premature auricular contraction with sinus rate of 120 beats per minute. After he had breathed oxygen for 5 minutes, and after fentanyl, 150 pg, had been given intravenously, the heart rate decreased to 100 beats per minute. Thiopental, 300 mg, was then given, followed by pancuronium, 8 mg, when the eyelash reflex was obtunded. Approximately 3 minutes after the pancuronium had been given and while the patient was being ventilated with 0 2 , the heart rate suddenly increased to 180 beats per minute. ECG revealed the tachycardia to be supraventricular in origin. Arterial blood gas tensions and serum electrolyte levels at that time were pH 7.42, P a q 38 torr, Pao, 438 torr (FIo, LO), HC0325 meq/L, Na+ 142 meq/L, and K+ 3.6 meq/L. Four successive intravenous doses of propranolol (0.25 mg) given over 10 minutes, and one intravenous dose of edrophonium, 15 mg, followed by left carotid sinus massage failed to affect the tachycardia. Anesthesia was deepened with additional thiopental (125 mg) but without slowing of heart rate. Up to this point, the patient’s blood pressure remained stable (systolic 140 to 165 mm Hg, diastolic 100 to 110 mm Hg) and there was no wheezing. In view of the intractable tachycardia, it was considered unwise to proceed with the operation. The larynx was, therefore, intubated after application of topical Iidocaine; and the patient was moved to the recovery room where mechanical ventilation was continued. Twenty minutes later, the tachycardia suddenly converted to normal sinus rhythm at a heart rate of 120 to 130 beats per minute. The aminophylline level at that time (8 hours after the last dose) was 8 pg/ml. Serum creatine phosphokinase (MB fraction) levels on three successive days thereafter were normal and a postoperative chest film in the recovery room was clear. ECGs taken on subsequent days showed continued existence of atrial ectopy. As aminophylline provided subjective relief, the patient continued to take this medication after surgery. In view of the atrial ectopy he was digitalized before discharge and treated nonoperatively.

Anesthetic Management During Liver Transplantation

Liver allotransplantation confronts the anesthesiologist with complex and unique physiological problems, all of them resulting from end-stage liver failure and the peculiar stages of this operation. Contrary to a preliminary belief that the repercussions of the anesthetic intervention in the patients was the basic management problem, clinical experience has shown that the centerpiece of management lies on the ability of the anesthesia team to deal with excessive blood transfusions and its hemodynamic and metabolic correlates. A better understanding of and experience with these problems has led to significant changes in our perioperative anesthetic management.

Methoxyflurane: Effects upon cardiac contractility, rhythmicity, and blood pressure in dogs

SummaryMethoxyflurane was administered to unpremedicated dogs in increasing and decreasing cpncentrations while normal pulmonary ventilation was rigidly maintained. Myocardial contractility, blood pressure, pulse rate, electrocardiogram, and electroencephalogram were recorded continuously.A progressive decrease in contractile force of the heart muscle resulted as the inhaled concentration of methoxyflurane increased. A parallel decrease in systolic, diastolic, and pulse pressure occurred. Sinus bradycardia and an alteration in repolarization of cardiac muscle accompanied the dynamic changes. A lag occurred in recovery of all cardiovascular functions and the EEG following withdrawal of the agent. Burst suppression appeared when hypotension below 90 mm. Hg occurred.A comparison of the results of this study with those previously reported is presented.R&#x00E9;sum&#x00E9;Nous avons fait inhaler à des chiens non prémédiqués des concentrations croissantes et décroissantes de méthoxyflurane alors quenous maintenions, par ventilation artificielle, un taux de C02 de 5.6 pour cent à la fin de ľexpiration. De façon continuelle, nous avons mesuré la contractilité ventriculaire à ľaide ďun dynamomdètre ad hoc. Nous avons également enregistré, de façon continue, la pression artérielle, le pouls, les tracés: électrocardiographique et électroencéphalographique.Nous avons observé que la force de contraction du myocarde diminuait à mesure qu’augmentait la concentration des vapeurs du méthoxyflurane. Si la concentration des vapeurs atteignait 2 pour qent, la force de contraction était diminuee de 48 pour cent. Les pressions—systolique, diastolique et la pression du pouls—diminuaient parallélement. Les modifications observées é la pression systolique étaient comparables aux modifications observées é la force de contraction. En même temps qu’apparaissaient ces modifications dynamiques, on pouvait observer ľexistence ďune bradycardie et une modification de la repolarisation du muscle cardiaque.A mesure que ľanesthésie s’approfondissait, ľactiiite rapide à bas voltage du tracé électroencéphalographique se modifiait en ondes lentes à haut voltage. En anesthesie profonde, ľactivité rapide concomitante disparaissait. On observait fréquemment des absences ďondes que nous avons attribuées à ľhypotension artérielle. Lorsque la pression artérielle demeurait au-dessus de 90 mm. Hg, ces absences n’apparaissaient pas.Aprés avoir discontinué ľadministration de ľagent, il s’écoulait un certain temps avant que les fonctions cardiovasculaires et ľactivité électroencéphalographique ne réapparaissent.

Anesthetic Management During Cardiac Transplantation

The anesthetic care for patients undergoing cardiac transplantation was first described by Ozinsky in 1967.1 In subsequent years only three other reports2—4 have highlighted the experiences of the most active heart transplant centers. This chapter will discuss the concepts and techniques employed at the University of Minnesota since inauguration of our cardiac transplantation program in 1978.