Morley Rosenbloom

Pharmacokinetics of Sufentanil in Patients Undergoing Abdominal Aortic Surgery

The authors determined the pharmacokinetics of sufentanil, 12.5 micrograms.kg-1 iv in patients undergoing elective abdominal aortic surgery. The mean age (+/- SD) of the ten patients was 68.4 +/- 7.9 yr; their mean weight was 74.4 +/- 19.1 kg. Six patients underwent aortobifemoral grafting and four had abdominal aortic aneurysm repair. Serum sufentanil concentrations were determined in samples drawn at increasing intervals over a 24-h period. A three-compartment pharmacokinetic model was fit to the concentration versus time data. Total drug clearance was 15.0 +/- 3.2 ml.min-1.kg-1. The volume of distribution at steady-state (Vdss) was 8.7 +/- 4.5 l.kg-1. The elimination half-time were positively correlated with patient age. There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of iv fluids given intraoperatively. In general surgical patients, the mean elimination half-time of sufentanil has been reported to be 2.7 h. When sufentanil is used in large doses as the primary anesthetic agent for patients undergoing abdominal aortic surgery, the long elimination half-time observed implies that recovery will take much longer than would have been anticipated from previously published pharmacokinetic data.

A Comparison of Desflurane and Isoflurane in Patients Undergoing Coronary Artery Surgery

Animal studies indicate that desflurane and isoflurane have similar hemodynamic effects when administered in equipotent anesthetic concentrations. The authors compared desflurane and isoflurane, used as primary anesthetics for patients undergoing elective coronary artery bypass surgery whose left ventricular ejection fractions were greater than 0.34. After induction of anesthesia with thiopental (dose 180 +/- 45 mg [mean +/- standard deviation]) and fentanyl, 10 micrograms.kg-1, either desflurane or isoflurane was administered to maintain systolic blood pressure within 70-120% of, and heart rates less than 120% of, the patients average preoperative values. If adjusting the end-tidal anesthetic concentration within the range of 0-2.0 MAC could not maintain these predefined hemodynamic limits, additional fentanyl or vasoactive drugs were used. Induction and maintenance of anesthesia was accompanied by a significant decrease in mean arterial pressure in both groups (desflurane 97 +/- 12 mmHg at control, decreasing to 71 +/- 5 mmHg during skin preparation; isoflurane 95 +/- 9 mmHg at control, 74 +/- 9 mmHg during skin preparation). One minute after sternotomy, mean arterial pressure in the isoflurane group had returned to control, 97 +/- 9 mmHg, which was significantly greater than in the desflurane group, 87 +/- 12 mmHg. Systolic arterial pressure was also significantly greater in the isoflurane group 1 min after intubation, during skin preparation, and 1 min after sternotomy. Otherwise, the hemodynamic effects of these volatile agents were similar. There were no differences between groups in the incidence of ECG changes indicative of myocardial ischemia prior to cardiopulmonary bypass, perioperative myocardial infarction, or perioperative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Premedication and high-dose fentanyl anesthesia for myocardial revascularization: a comparison of lorazepam versus morphine-scopolamine

Using a randomized double-blind placebo-controlled experimental protocol, the authors compared two premedication regimens in 42 patients undergoing elective myocardial revascularization. Group L patients (n = 23) received lorazepam 0.06 mg/kg po 90 min preoperatively, while group M patients (n = 19) received morphine 0.1 mg/kg im, plus scopolamine 0.006 mg/kg im 60 min preoperatively. Anesthesia was induced with fentanyl 100 micrograms/kg and atracurium 0.50 mg/kg administered over 10 min. The treatment groups did not differ significantly with respect to the degree of sedation or anxiolysis achieved, or the rapidity of induction with fentanyl. Premedication significantly influenced the hemodynamic response to anesthetic induction. Hemodynamics were stable post-induction in group M, but cardiovascular depression was noted in group L. Control heart rate (HR) was lower in group L. The HR, arterial pressure, and cardiac index were significantly lower, following both induction and intubation, in group L. Following sternotomy hemodynamics were identical in both groups. Serum fentanyl concentration was significantly higher during intubation in group L, probably secondary to the pharmacokinetic consequences of a decreased CI. New electrocardiographic evidence of myocardial ischemia did not occur in either group. Based on their findings with fentanyl-at-racurium, and their review of the literature, the authors speculate that premedication exerts a significant hemodynamic effect during induction with other narcotic-relaxant combinations.

Alfentanil pharmacokinetics in patients undergoing abdominal aortic surgery

The pharmacokinetics of alfentanil, 300 μg · kg−1 IV, were determined in patients undergoing elective abdominal aortic reconstruction. The mean age (± SD) of the patients wax 64.3 ±7.4 yr: their mean weight was 74.7 ± 13.8 kg. Five patients underwent aneurysm repair and six had aortobifemoral grafting. Serum alfentanil concentrations were measured by gas-liquid chromatography in samples drawn at increasing intervals over a 24-hr period. A three-compartment model was fitted to the concentration versus time data. The volume of the central compartment and the volume of distribution at steady state (Vdss) were 0.044 ± 0.022 and 0.63 ± 0.32 L · kg−1, respectively. Total drug clearance was 6.4 = 1.9 ml · min−1 · kg−1. The elimination half-time was 3.7 ± 2.6 hr. Patient age was positively correlated with both Vdss and elimination half-time. There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of IV fluids infused intraoperatively. In general surgical patients, the elimination half-time of alfentanil has been reported to be 1.2–2.0 hr. Although the elimination half-time of alfentanil was longer in patients undergoing abdominal aortic surgery, alfen-tanil was eliminated much faster than either fentanyl or sufentanil in this patient population.RésuméNous avons tracé le profil pharmacocinétique d’une dose intraveineuse de 300 μg · kg−1 d’alfentanil lors de reconstructions électives de l’aorte. Cinq patients subirent une résection d’anévrysme et six autres, un pontage aortobifémoral. Ils avaient en moyenne 64,3 ± 7,4 ans et pesaient 74,7 ± 13,8 kg. On mesura les concentrations sériques d’alfentanil par chromatographie gaz-liquide sur des échantillons prélevés à intervalles croissants pendant 24 h. L’évolution temporelle des concentrations était celle d’un modèle pharmacocinétique tri-compartimental. Le compartiment central avait un volume de 0,044 ± 0,022 L · kg−1 et le volume de distribution à l’équilibre (Vdss était de 0,63 ± 0,32 L · kg−1: la clairance était de 6.4 ±1,9 ml · min−1 · kg−1 et la demievie d’élimination, 3,7 ± 2,6 h. Il y avait une corrélation positive entre l’âge du patient, le Vdss et la demievie. Les variables pharmacocinétiques étaient toutefois indépendantes de la durée du clampage aortique et de l’intervention, de même que du débit et du volume des liquides perfusés par voie veineuse pendant l’opération. Même si elle s’est avérée plus longue que celle de 1,2 à 2 h observée en chirurgie générale, la demievie d’élimination de l’alfentanil est beaucoup plus courte que celles du fentanyl et du sufentanil lors de chirurgie aortique.

Drug Interactions with Sufentanil Hemodynamic Effects of Premedication and Muscle Relaxants

Induction of anesthesia with synthetic opioids is occasionally accompanied by undesirable hemodynamic changes such as tachycardia and hypertension, or bradycardia and hypotension. We hypothesized that drug interactions cause many of these adverse responses. Therefore, we conducted a randomized double-blind study to investigate the interactive effect of premedication and muscle relaxants on the hemodynamic response to induction with intravenous (iv) sufentanil 10 micrograms.kg-1. Eighty patients with left ventricular ejection fraction greater than or equal to 0.40, undergoing elective coronary artery surgery, were premedicated with either morphine 0.1 mg.kg-1 and scopolamine 6 micrograms.kg-1 intramuscularly, or lorazepam 60 micrograms.kg-1 orally, and paralyzed with either pancuronium 0.1 mg.kg-1 or vecuronium 0.1 mg.kg-1 iv. The four treatment groups were SP (morphine-scopolamine + pancuronium), LP (lorazepam + pancuronium), SV (morphine-scopolamine + vecuronium), and LV (lorazepam + vecuronium). Hemodynamics were recorded at three time periods: 1) control, 2) induction, and 3) intubation. Premedication-relaxant interactions significantly affected hemodynamics. In group SP, mean heart rate (HR) increased significantly on induction (56 +/- 11 to 69 +/- 13 beats.min-1), while mean arterial pressure (MAP) and cardiac index (CI) were unchanged. HR, MAP, and CI were significantly higher after induction in group SP compared to the other three groups. In group LP, mean HR increased less than in group SP (56 +/- 8 to 62 +/- 14 beats.min-1), whereas MAP and CI declined significantly. In group SV, HR and CI were unchanged, but MAP declined significantly. In group LV, HR was stable, whereas both MAP and CI declined significantly. The incidence of pharmacologic interventions during the study period also differed significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized double- blind comparison of fentanyl and sufentanil anaesthesia for coronary artery surgery

Using a randomized double-blind protocol the authors compared two narcotic anaesthetic regimens in 33 patients with good ventricular function undergoing coronary artery surgery. After premedication with morphine and scopolamine, patients received either fentanyl 100 μg.kg-1 (n = 16), or sufentanil 15 μg.kg-1 (n = 17), intravenously (IV) over 10 min to induce anaesthesia. Metocurine 0.42 mg kg-1 provided muscle relaxation. No further IV anaesthetic agents were given. The haemodynamic response to induction, intubation, and surgery, differed minimally between agents. The degree of rigidity on induction was identical with both agents, as were the intervals following induction at which patients lost consciousness, regained consciousness, or met criteria for extubation. However, the interval until extubation criteria were met did correlate with the duration of cardiopulmonary bypass. Sufentanil 15 μg.kg-1, was clinically indistinguishable from fentanyl 100 μg.kg-1, when used as the primary anaesthetic agent for coronary surgery.RésuméUtilisant un protocole randomisé à double insu les auteurs ont comparé deux régimes ďanesthésie au narcotic chez 33 patients ayant une bonne fonction ventriculaire et devant subir une chirurgie coronarienne. Après prémédication avec de la morphine et scopolamine, les patients ont reçu soit du fentanyl 100 μ.g·kg-1 (n = 16) ou du sufentanil 15 μg·kg-1 (n = 17), par voie intraveineuse en dix minutes afin ďinduire ľanesthésie. La métocurine 0.42 mg·kg-1 fut administrée pour relâchement musculaire. Aucune autre injection intraveineuse ďagent anesthésique ne fut donnée. La réponse hémodynamique à ľinduction, intubation et chirurgie a démontré une différence minime entre les deux agents. Le degré de rigidité à ľinduction était identique avec les deux agents. Il en fut de m ême pour les temps de perte de conscience, regain de conscience ou les critères ďextubation. Cependant ľintervalle pour atteindre les critères requis de ľextubation étaient en corrélation avec la durée de la CEC. Le sufentanil 15 μ,g·kg-1 n’étaient pas cliniquement différent du fentanyl 100 μg·kg-1 lorsqu’utilisé comme seul agent anesthésique pour la chirurgie coronarienne.

Dose-response to anaesthetic induction with sufentanil: haemodynamic and electroencephalographic effects

PurposeTo determine the effect of a five-fold variation in sufentanil dose on the haemodynamic and electroencephalo graphic (EEG) response to anaesthetic induction and tracheal intubation.MethodsThirty-four patients undergoing elective coronary artery bypass grafting (CABG) participated in this randomized double-blind study. Patients in Group L (n= 17) received 3 μg · kg−1 sufentanil and those in Group H (n= 17) 15 μg · kg−1. Premedication was 60 μg · kg−1 lorazepam po. Anaesthesia and neuromuscular blockade were induced by infusing sufentanil and 0.15 mg · kg−1 vecuronium iv over five minutes. Haemodynamic data and the electroencephalographic (EEG) spectral edge were acquired by computer and compared at Control, Induction and Intubation.ResultsSufentanil dose did not affect the haemodynamic or EEG response at end-induction. No bradyarrhythmias occurred, and the incidence of hypotension was 12% in both groups. However, during induction apparent electromyographic artifacts and a transiently greater increase in heart rate were observed in Group H. The serum sufentanil concentration at Induction was 6.1 ± 1.8 ng · ml−1 in Group L and 25.4 ± 8.8 ng · ml−1 in Group H, and did not correlate with haemodynamic changes. No patient recalled any intraoperative event.ConclusionIncreasing sufentanil dose from 3 to 15 μg · kg−1 does not influence the ultimate haemodynamic response to induction. Combined with lorazepam premedication, 3 μg · kg−1 sufentanil produces near-maximal haemodynamic and EEG effects and is adequate for induction and tracheal intubation of patients undergoing CABG. Sufentanil 15 μg · kg−1 is no more efficacious, and causes transient cardiovascular stimulation.RésuméObjectifDéterminer les effets hémodynamiques et électroencéphalographiques (EEG) d’une dose quintuple de sufentanil sur l’induction de l’anesthésie et l’intubation de la trachée.MéthodesTrente-quatre patients subissant une chirurgie de revascularisation myocardique (CRVM) non urgente participaient à cette étude aléatoire conduite à double insu. Les patients du groupe L (n= 17) recevaient sufentanil 3 μg · kg−1 et ceux du groupe H (n = 17) 15 μg · kg−1. Tous étaient prémédiqués au lorazepam 60 μg kg−1 per os. L’anesthésie et la curarisation étaient initiées en perfusant le sufentanil et le vécuronium 0,15 mg kg−1 iv en cinq minutes. Les données hémodynamiques et l’EEG spectral comprimé étaient recueillies sur ordinateur et comparées à la phase de contrôle, à l’induction et au moment de l’intubation.RésultatsLe sufentanil n’a pas eu d’effets hémodynamiques ou EEG à l’induction. On n’a pas observé de bradycardie et l’incidence d’hypotension a été de 12% pour les deux groupes. Cependant, pendant l’induction, des perturbations visibles à l’EEG et une augmentation transitoire plus importante de la fréquence cardiaque étaient observés dans le group H. La concentration sérique de sufentanil à l’induction était de 6, 1 ± 1, 8 ng ml−1 pour le groupe L et de 25, 4±8, 8 ng · ml−1 pour le groupe H et n’était pas en corrélation avec les changements hémodynamiques. Aucun des patients n’a mentionné un rappel d’événements peropératoires.ConclusionLaugmentation de la posologie du sufentanil de 3 à 15 mg kg−1 n’a pas d’unfluence sur la réponse hémodynamique en fin d’induction. Associé à une prémédication de lorazepam, le sufentanil 3 μg kg−1 produit des effets hémodynamiques et EEG presque maximaux et est adéquat pour l’induction et l’intubation de la trachée de patients subissant une CRVM. Le sufentanil 15 μg · kg−1 n’est pas plus efficace et provoque une stimulation cardiovasculaire transitoire.

Fentanyl oxygen anaesthesia for abdominal aortic surgery

Patients who present for abdominal aortic surgery often have significant atherosclerotic disease which may involve the coronary arteries. Haemodynamic responses occurring during fentanyl (100 μ.g.kg-1 ) oxygen anaesthesia for abdominal aortic surgery were studied in 16 patients. Anaesthesia was induced with fentanyl 100 μ.g.kg-1 with no supplemental doses and metocurine-pancuronium mixture (4:1). In 13 of 16 patients hyperdynamic circulatory responses to surgical stimuli required treatment prior to aortic cross-clamping. Interventions instituted were sodium nitroprusside or nitroglycerin (n = 13), propranolol (n = 4), and diazepam (n = 4). The serum fentanyl concentration at time of response to surgical stimulus was 18.5 ± 5.6 ng.min-1 (range 7–27 ng.min-1; time from induction 71 ± 49 min, n = 9). Eleven of the 16 patients required treatment for postoperative hypertension. Five of the 16 patients developed myocardial ischaemia, defined as ST segment depression greater than O.ImV, at some time during the operative procedure. Unsupplementedfentanyl anaesthesia (100 μg.kg-1) was unable to maintain a hypodynamic circulation in patients having abdominal aortic operations.RésuméLes patients se présentant pour chirurgie aortique abdominale présentent souvent une maladie athérosclérotique pouvant atteindre les coronaires. Les réponses hémodynamiques survenant lors de la chirurgie sur l’aorte abdominale et une anesthésie aufentanyl (100 μg.kg-1) — O2 ont été étudiées chez 16 patients. L’anesthésie était induite avec du fentanyl 100 μg.kg-1 sans dose supplémentaire de mélange et métocurinelpancuronium (4:1). Pour 13 des 16patients les réponses hyperdynamiques au stimulus chirurgical ont requis un traitement avant le clampage aortique. Les interventions incluent la nitroprussiate de soude ou nitroglycérine (n = 13), propranolol (n = 4), diazepam (n = 4). La concentration sérique de fentanyl au temps de réaction au stimulus chirurgical était de 18.5 ± 5.6 ng.ml-1 (écart: 7–27 ng.ml-1), le temps à partir de l’induction 71 ± 49 min. (n = 9). Onze des 16 patients ont requis un traitement pour l’hypertension post-opératoire. Cinq des 16 patients ont développé une ischémie myocardique définie comme étant une dépression du segment ST supérieur à 0.1mV, lors de la procédure chirurgicale. L’anesthésie au fentanyl, celle (100 μg.kg-1) était incapable de maintenir un état hypodynamique chez les patients devant subir une chirurgie sur l’aorte abdominale.

A two-center study evaluating the hemodynamic and pharmacodynamic effects of cisatracurium and vecuronium in patients undergoing coronary artery bypass surgery.

OBJECTIVEnTo determine the hemodynamic and pharmacodynamic effects of rapid bolus administration of cisatracurium compared with vecuronium.nnnDESIGNnA randomized, prospective, double-blind study.nnnSETTINGnTertiary-care university hospitals.nnnPARTICIPANTSnSeventy-nine adult patients with diagnosed coronary artery disease (CAD).nnnINTERVENTIONnElective coronary artery bypass graft surgery (CABG).nnnMEASUREMENTS AND MAIN RESULTSnPatients were randomly divided into four groups. Patients received a rapid bolus of two or four times the 95% peak depression of twitch (ED95) of either cisatracurium (groups 1 and 2) or vecuronium (groups 3 and 4). Three minutes after a midazolam induction, all patients received a rapid bolus administration of either study drug. Maintenance of anesthesia was with a standardized propofol-sufentanil-oxygen anesthetic. Patients were monitored with radial and pulmonary artery catheters and electromyography. End points of the study were hemodynamic stability at induction, after bolus administration of study drugs, and after intubation; the quality of intubating conditions; drug interventions to correct hemodynamic instability; the onset, duration, and recovery of neuromuscular function; and drug cost. Mean arterial pressure (MAP) and heart rate (HR) decreased in a similar proportion in all four groups after induction while, following study drug administration, MAP and HR did not change significantly. Both cisatracurium groups required more boluses to maintain neuromuscular block, but spontaneous recovery rates were faster. Both agents, but cisatracurium to a lesser degree, showed increased duration with repeated maintenance doses. Both agents afforded good to excellent intubating conditions, but the cost of cisatracurium was significantly less.nnnCONCLUSIONnThe authors conclude there is no evidence of a hemodynamic difference between the two neuromuscular blocking drugs (NMBDs). There are some clinical and cost advantages in favor of cisatracurium.

Does sufentanil concentration influence isoflurane requirements during coronary artery bypass grafting

OBJECTIVEnTo search for concentration-related suppression of hemodynamic responsiveness by sufentanil.nnnDESIGNnProspective, randomized, double-blind study.nnnSETTINGnUniversity hospital.nnnPARTICIPANTSnPatients undergoing elective coronary artery bypass grafting (CABG).nnnINTERVENTIONnPatients were assigned to target effect-site sufentanil concentrations of 1.5 ng/mL (group L; n = 14), 3.0 ng/mL (group M; n = 13), or 4.5 ng/mL (group H; n = 12). Sufentanil was administered by computer-assisted continuous infusion. Isoflurane was used to maintain intraoperative hemodynamics near preoperative values.nnnMEASUREMENTS AND MAIN RESULTSnHemodynamics, the electroencephalographic spectral edge (SE95), and end-tidal isoflurane concentration (ET-ISO) were measured every 10 to 30 seconds during the prebypass period. Serum sufentanil concentration was measured at intervals. Prebypass serum sufentanil concentrations were stable, averaging 3.0 +/- 0.7, 5.1 +/- 1.1, and 7.1 +/- 1.3 ng/mL in groups L, M, and H, respectively. The groups did not differ with respect to the speed of induction, intraoperative hemodynamics, incidence of isoflurane use, or isoflurane concentrations required. ET-ISO and serum sufentanil levels were not correlated. Among seven group L patients who did not require isoflurane, the average prebypass serum sufentanil concentration ranged from 1.7 to 3.3 ng/mL.nnnCONCLUSIONnSufentanil does not induce concentration-related suppression of hemodynamic responsiveness over the range studied. A stable serum sufentanil concentration of 3.0 +/- 0.7 ng/mL induces the maximal opioid effect and need not be exceeded in patients undergoing CABG. A sufentanil concentration of 1.7 ng/mL provides clinically adequate anesthesia without supplementation in some premedicated patients undergoing CABG.