Martin D. Sokoll

A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy : propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide

Background:Different anesthetic agents have different effects on cerebrovascular physiology. However, the importance of these differences In neuroanesthetic practice are unclear. In an effort to determine whether important clinical differences are present, the authors compared three anesthetic techniques in 121 adults undergoing elective surgical removal of a supratentorial, intracranial mass lesion. Methods:Patients were assigned randomly to one of three groups. In group 1 (n=40), anesthesia was induced with propofol and maintained with fentanyl (≊10 µg/kg load, 2-3 µg · kg-1 · h-1 infusion) and propofol (50-300 µg · kg-1 · mln-1). In group 2 (n=40), anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide. Up to 2 µg/kg fentanyl was given after replacement of the bone flap. In group 3 (n=41), anesthesia was induced with thiopental and maintained with fentanyl (≊10 µg/kg load, 2-3 µg · kg-1 · h1 infusion), nitrous oxide, and low-dose Isoflurane, if required. Blood pressure, heart rate, expired gas concentrations, and ventilatory parameters were recorded automatically in all patients. Epidural intracranial pressure (ICP) was measured via the first burr hole, brain swelling was rated at the time of dural opening, and emergence was monitored closely. Preoperative computed tomography or magnetic resonance imaging scans were evaluated, and pre- and postoperative neurologic exams were performed by a neurosurgeon unaware of group assignments. Total hospital stay (days) and total hospital cost (exclusive of physician charges) also were reviewed. Results:During induction, higher heart rates were seen in isoflurane/nitrous oxide patients, whereas mean arterial pressure was ≊10 mmHg less during the maintenance phase (compared with both other groups). Otherwise, there were few intergroup hemodynamic differences. While there were no clinically important intergroup differences in mean ICP (±SD)—group 1, ICP=12 ± 7 mmHg; group 2,15 ± 12 mmHg; group 3, ICP=11 ± 8 mmHg—more isoflurane/nitrous oxide patients (nine, group 2) had an ICP £24 mmHg than in the other groups (two each). Emergence was, overall, more rapid with fentanyl/nitrous oxide. For example, the median time until the patient could be awakened by quiet verbal command, e.g., “Open your eyes,” was 5 min, versus 10 min in the other groups. There were no relationships between ICP and any measurement of emergence (e.g., time to response to commands). Seven of 41 (17%) fentanyl/nitrous oxide patients vomited In the early postoperative period, compared with only 1 of 40 (2.5%) of those given propofol/fentanyl and 2 of 40 (5%) receiving isoflurane/nitrous oxide (P=0.03). There were no differences in the incidence of new postoperative deficits, total hospital stay, or cost. Conclusions:Although there are modest differences among the three tested anesthetics, short-term outcome was not affected. These results indicate that, despite their respective cerebrovascular effects, all of the anesthetic regimens used were acceptable in these patients undergoing elective surgery.

Comparison of Remifentanil and Fentanyl in Patients Undergoing Craniotomy for Supratentorial Space-occupying Lesions

BackgroundRemifentanil hydrochloride is an ultra-short-acting, esterase-metabolized micro-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions.MethodsSixty-three adults gave written informed consent for

Alterations in Cerebral Blood Flow, Oxygen Metabolism, and Electrical Activity Produced by High Dose Sodium Thiopental

High dose barbiturate therapy is being used with increasing frequency in the management of a widening spectrum of neurological disorders. Accurate regulation of the barbiturate dose is essential to maximize cerebral vasoconstriction and reduce brain metabolism while avoiding the cardiovascular depressant side effects of the drug. The purpose of this study was to determine whether the electroencephalogram (EEG) could be used to regulate administration of the agent. In nine mongrel dogs cerebral blood flow (CBF) was determined using the radioactive microsphere technique. After the determination of control CBF, a slow infusion of sodium thiopental was begun. CBF determinations were repeated when the periods of burst suppression in the EEG over several minutes averaged 30, 60, 120, and 240 seconds. CBF and oxygen metabolism showed a nearly identical pattern of a precipituos drop from control levels reaching a plateau at burst suppression between 30 and 60 seconds. Changes in cerebrovascular resistance were of a similar but opposite nature. Significant increases in heart rate occurred with burst suppression of 30 seconds, whereas the arterial pressure and cardiac index decreased with burst suppression between 30 and 60 seconds. In this study cerebral metabolic depression and vasoconstriction from sodium thiopental reached a plateau when sufficient barbiturate was administered to produce EEG burst suppression of between 30 and 60 seconds. At this level there was no important cardiovascular depression. Administration of additional barbiturates significantly decreased systemic arterial pressure and cardiac output, but produced no further decrement in the cerebral metabolic rate of oxygen or the CBF. There was no predictable relationship between cerebral metabolism or cardiovascular function and blood levels of sodium thiopental.

Safety and Efficacy of Atracurium (BW33A) in Surgical Patients Receiving Balanced or Isoflurane Anesthesia

Atracurium was administered in a dose range of 0.027-0.4 mg/kg and dose-response curves were established for both balanced and isoflurane anesthetic techniques. With balanced anesthesia, ED50 and ED95 were 0.12 and 0.27 mg/kg, respectively, while with isoflurane they were 0.07 and 0.13 mg/kg and the least-squares regression line R2 values were 0.71 and 0.64, respectively. With balanced anesthesia there was a significant increase in systolic blood pressure at the 0.04 mg/kg dose (P = 0.02), while with isoflurane the systolic and diastolic blood pressures decreased at the 0.3 mg/kg dose (P less than 0.03). These changes were clinically insignificant. Atracurium is a potent nondepolarizing muscle relaxant which is potentiated by isoflurane. Its cardiovascular effects appear clinically nonsignificant. There is no evidence of histamine release.

The Neuromuscular Blocking and Cardiovascular Effects of Doxacurium Chloride in Patients Receiving Nitrous Oxide Narcotic Anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01–0.06 mg·kg-1). Patients in a control group (group B) (n=12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg·kg-1 and 0.023 mg·kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 ± 1.3 min and 7.6 ± 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 ± 8.7 min. With larger doses of doxacurium, 0.04 mg·kg-1 (1.7 × ED95) and 0.05 mg·kg-1 (2.2 × ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 ± 24.8 and 204.0 ± 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt. After administration of 0.04 mg · kg-1 of doxacurium or 0.08 mg · kg-1 of pancuronium, the time for spontaneous recovery to 25% of control twitch height recovery was 77.4 ± 7.5 min (n = 23) and 71.4 ± 6.7 min (n = 10), respectively. When identical multiple maintenance doses of doxacurium were administered, the subsequent neuromuscular block following each maintenance dose was of similar magnitude and duration. At 1,2, and 5 min following pancuronium, heart rate and mean blood pressure increased. Following doxacurium small decreases in mean blood pressure occurred at 2 and 5 min, while heart rate decreased 5 min following drug injection. Doxacurium is a new, long-acting, nondepolarizing relaxant. Further study is warranted to assess the cardiovascular effects of this neuromuscular blocking drug in patients with cardiovascular disease.

Use of Anticoagulants, Electroencephalographic Monitoring, and Barbiturate Cerebral Protection in Carotid Endarterectomy

This paper describes a treatment protocol for threatened stroke in patients to carotid endarterectomy. The protocol includes the use of perioperative anticoagulation, intraoperative electroencephalographic (EEG) monitoring, and hypertension or barbiturates to protect the brain against documented ischemia intraoperatively. The rational and methods for protecting the patient from the threat of thromboembolism and cerebral ischemia during each of the periods of specific risk are discussed. The most unique feature of this protocol is the use of thiopental-induced EEG burst suppression for ischemia unresponsive to hypertension during carotid clamping, which has obviated the use of a potentially dangerous and cumbersome in-line arterial shunt.

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg · kg−1 to 0.25 mg · kg−1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg · kg−1 and 0.053 mg · kg−1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg · kg− 1 mivacurium was 15.3 ± 1.0 min and 21.5 ± 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25–75 per cent) between initial bolus dose (6.1 ± 0.5 min), repeat bolus doses (7.6 ± 0.6 min), mivacurium infusion (6.7 ± 0.7 min) and succinylcholine infusion (6.8 ± 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg · kg−1. Bolus administration of 0.20 mg · kg−1 or 0.25 mg · kg−1 of mivacurium decreased MAP from 78.2 ± 2.5 to 64.0 ± 3.2 mmHg (range 12–59 per cent of control) (P < 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.RésuméLes effets cardiovasculaires et neuromusculaires du chlorure de mivacurium ont été étudiés lors d’une anesthésie au narcotique (fentanyl) protoxyde d’azote-oxygène (n = 90) et isoflurane (ISO) protoxyde d’azote-oxygéne (n = 45). En plus, un groupe séparé (n = 9) a reçu du succinylcholine lors d’une anesthésie au fentanvl afin de comparer ces effets neuromusculaires avec le mivacurium. Le mivacurium a été initialement administré comme un bolus unique les doses de 0,03 mg · kg−1 et 0,25 mg · kg−1 afin d’étudier la courbe dose-réponse et les effets cardiovasculaires du mivacurium. Le bloc neuromusculaire (NMB) a été mesuré en enregistrant la réponse au twitch de l’adducteur du pouce après stimulation du nerf cubital (0.15 Hz, 0.2 ms voltage supramaximal). Les valeurs de ED95 du mivacurium ont été estimées à 0,073 mg ·kg−1 et 0,053 mg · kg−1 respectivement pour le groupe fentanyl et ISO. La durée du bloc (temps à partir de l’injection à la recouvrance à 95 pour cent) pour une dose de 0,05 mg · kg−1’ de mivacurium était de 15,3 ± 1,0 min. et 21,5 ± 1,3 min. respectivement pour le groupe fentanyl et le groupe ISO. L’index de recouvrance (25–75 pour cent) entre le bolus initial (6,1 ± 0,7 min) la dose de rajout (7,6 ± 0,6 min) et la perfusion de mivacurium (6,7 ± 0,7 min) et la perfusion de succinycholine (6,8 ± 1,8 min) n’était pas significativement différent. On a observé des changements minimes dans la pression artérielle moyenne (MAP) ou la fréquence cardiaque (HR) après le bolus de mivacurium jusqu’à 0,15 mg · kg−1. Une administration en bolus de 0,20 mg · kg−1 ou 0,25 mg · kg−1 de mivacurium a diminué la pression artérielle moyenne de 78,2 ± 2,5 à 64.0 1 3,2 mmHg (écart de 12–59 pour cent du contrôle) (P < 0.05). Les mêmes doses lorsque administrées lentement au-dessus de 30 secondes ont produit des changements minimes de la pression artérielle moyenne et de la fréquence cardiaque.

Vascular spasm in cat cerebral cortex following ischemia.

The reaction of brain parenchymal vessels in areas of no-reflow following ischemia in cats was evaluated. A method was devised by which brain biopsies following ischemia were quickly frozen at −170°C, sections were cut and stained and vessel internal and external diameter measured. Vessels in the no-reflow areas had smaller internal and external diameters and thicker walls when compared to adjacent reflow areas as well as to normal control animals. By utilizing a 2-way analysis of variance in which reflow versus noreflow vessel diameters were compared by region the differences were found to be statistically significant (p < 0.05). The data raise the possibility that there may exist normal regional differences in the size of cerebral vessels.

Effect of various antibiotics on neuromuscular transmission

Abstract The effects of streptomycin, neomycin, kanamycin, polymixin and gentamycin on release of acetylcholine from nerve terminal and on muscle twitch were studied using the frog sciatic nerve-gastrocnemius muscle preparation. The first 4 agents were found to be devoid of any inhibitory action on prejunctional acetylcholine release while producing myoneural blockade. Gentamycin reduced acetylcholine output concomitant with myoneural blockade. It is concluded that the first 4 antibiotics act postsynaptically while gentamycin has a presynaptic component of action.

Ketamine: Myoneural activity and interaction with neuromuscular blocking agents☆

Abstract The effects of combined administration of neuromuscular agents and the nonbarbiturate anesthetic, ketamine. HC1 (KET), were studied using the cat sciatic nerve gastrocnemius muscle preparation. KET, in doses of 1 and 2 mg/kg i.v., was found to prolong the recovery time of neuromuscular blockade induced by both d-tubocurarine chloride and decamethonium bromide. Potentiation of muscle twitch by edrophonium chloride was antagonized by KET in doses of 1 and 2 mg/kg i.v. Investigation of the action of KET on neuromuscular transmission was carried out in the frog sartorius muscle by evaluation of changes in miniature end-plate potential (mepp) recordings. KET was found to have no effect on mepp frequency, but reduced mepp amplitude as well as the sensitivity of the end-plate to iontophoretically applied acetylcholine. It was concluded that interactions between KET and neuromuscular agents are due to a reduction of muscle end-plate sensitivity.