Influence of sufentanil on cerebral metabolism and circulation in the rat

The authors examined the effects of large intravenous doses of sufentanil (5-160 micrograms/kg) on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in rats. CBF and CMRO2 were measured by a modified Kety-Schmidt technique using 133Xenon washout. Progressive decreases in CBF and CMRO2 occurred in animals receiving sufentanil. The maximum decrease was 53% and 40% for CBF and CMRO2 respectively, at a dose of 80 micrograms/kg. The values for CBF and CMRO2 in this group were 105 +/- 10 ml X 100 g-1 X min-1 (mean +/- SEM) and 6.5 +/- 0.5 ml X 100 g-1 X min-1, respectively, compared with 226 +/- 28 ml X 100 g-1 X min-1 and 10.9 +/- 1 ml X 100 g-1 X min-1 in the control group, which received N2O 70% in oxygen. Larger doses of sufentanil did not cause further significant changes in CBF and CMRO2. Sharp waves appeared on the electroencephalogram (EEG) of all the animals following sufentanil injection, and some animals had EEG changes develop consistent with seizure activity. This seizure-like activity appeared to consist of a single episode of short duration in the groups receiving 5, 10, and 20 micrograms/kg sufentanil. The incidence and frequency of seizure activity increased in the groups receiving higher doses of sufentanil, although the duration of seizures was still short. The results of this study indicate that sufentanil causes a significant decrease in CBF and CMRO2 similar to that previously reported for fentanyl, and high doses of sufentanil may cause frequent seizure-like patterns appearing on EEG.     

Cerebral effects of high-dose midazolam and subsequent reversal with Ro 15-1788 in dogs

The effects of a continuous high-dose infusion of midazolam on cerebral function, metabolism, and hemodynamics were studied in nine dogs receiving a spinal anesthetic and breathing 65% nitrogen/35% oxygen. In five dogs, the effects of 65% nitrous oxide (N2O) inspired and the benzodiazepine antagonist Ro 15-1788 were also examined. Midazolam was infused at a rate of 0.66 mg.kg-1.min-1 for 60 min for a total dose of 40 mg.kg-1. Cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) (measured by venous outflow technique) both decreased until a plateau level was reached at approximately 75% of control values (4.0 +/- 0.2 ml.min-1.100 g-1 and 49 +/- 3 ml.min-1.100 g-1, respectively, mean +/- SEM). This occurred after 6-10 mg.kg-1 of midazolam, corresponding to serum midazolam levels between 18.4 +/- 3.8 and 31.2 +/- 3.3 micrograms.ml-1. Serum midazolam levels increased throughout the midazolam infusion, reaching a mean value of 53 +/- 5.5 micrograms.ml-1 by the end of the midazolam infusion. A similar plateau was seen for changes in the electroencephalogram (EEG), which never developed burst suppression. Five dogs inspired 65% nitrous oxide/35% oxygen during minutes 30-45 of the midazolam infusion, rather than 65% nitrogen/35% oxygen. Nitrous oxide had no effect upon CMRO2, but significantly increased CBF when compared to dogs receiving nitrogen. Ro 15-1788, 1.0 mg.kg-1 caused a return of CMRO2 and EEG activity to control levels. CBF and intracranial pressure (ICP) increased markedly, to greater than control levels immediately following Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of halothane,enflurane and isoflurane on the end-systolic pressure-length relationship

Myocardial contractility was measured using the end-systolic pressure-length (ESPL) relationship in dogs subjected to increasing concentrations of halothane (0.5-2 per cent), enflurane (0.77-2.6 per cent) or isoflurane (0.70-2.13 per cent), combined with an infusion 7 micrograms X kg-1 X min-1 of fentanyl, after induction of anaesthesia with 15 mg X kg-1 thiopentone. The relationship between the concentrations of the different drugs and contractility (ESPL) can best be described by ESPL = a + b/(MAC fraction) where "a" is a constant and "b" is the slope of the curve relating ESPL to MAC. At 1.0 MAC values, the ESPL for halothane (69.04 +/- 25.83 mmHg X mm-1) did not differ from that of isoflurane (63.19 +/- 17.36 mmHg X mm-1). However, the myocardial contractility during 1.0 MAC halothane and isoflurane anaesthesia was better preserved than that of enflurane (38.66 +/- 9.73 mmHg X mm-1: p less than 0.01, p less than 0.05 respectively).     

Esmolol for control of increases in heart rate and blood pressure during tracheal intubation after thiopentone and succinylcholine

Esmolol, an ultra-short-acting cardioselective beta-adrenergic blocker, was investigated in a double-blind prospective protocol for its ability to control haemodynamic responses associated with tracheal intubation after thiopentone and succinylcholine. Thirty ASA physical status I patients received a 12-minute infusion of esmolol (500 micrograms X kg-1 X min-1 for four minutes, then 300 micrograms X kg-1 X min-1 for 8 minutes) or saline. Five minutes after the start of the drug/placebo infusion, anaesthesia was induced with 4 mg X kg-1 thiopentone followed by succinylcholine for tracheal intubation. Prior to induction esmolol produced significant decreases in heart rate (HR) (9.3 +/- 1.8 per cent) and rate-pressure product (RPP) (13.1 +/- 1.8 per cent), systolic blood pressure (SAP) (4.3 +/- 1.5 per cent) and mean arterial blood pressure (MAP) (1.7 +/- 2.0 per cent). Increases in HR, SAP and RPP after intubation were approximately 50 per cent less in patients given esmolol compared to patients given placebo. There were highly significant differences in HR (p less than 0.0001), and RPP (p less than 0.0005) and significant differences in SAP (p less than 0.05) when the maximal esmolol post-intubation response was compared to the maximal placebo response. Infusion of esmolol in the dose utilized in this study significantly attenuated but did not completely eliminate cardiovascular responses to intubation.     

CBF and CMRO2 during Continuous Etomidate Infusion Supplemented with N2O and Fentanyl in Patients with Supratentorial Cerebral Tumour. A Dose-Response Study

In 14 patients with supratentorial cerebral tumours with midline shift below 10 mm, CBF and CMRO2 were measured (Kety & Schmidt) during craniotomy. The anaesthesia was continuous etomidate infusion supplemented with nitrous oxide and fentanyl. The patients were divided into two groups. In Group 1 etomidate infusion of 30 micrograms kg-1 min-1 was used throughout the anaesthesia, and CBF and CMRO2 were measured twice. In this group CMRO2 (means +/- s.d.) averaged 2.31 +/- 0.43 ml O2 100 g-1 min-1 70 min after induction and 2.21 +/- 0.38 ml O2 100 g-1 min-1 130 min after induction. In Group 2 the etomidate infusion was increased from 30 to 60 micrograms kg-1 min-1 after the first study and a significant fall in CMRO2 from 2.52 +/- 0.56 to 1.76 +/- 0.40 ml O2 100 g-1 min-1 was found. Simultaneously, a significant fall in CBF was observed. The CO2 reactivity was preserved during anaesthesia.     

Cerebral effects of nitrous oxide when added to low and high concentrations of isoflurane in the dog

The purpose of this canine study was to examine the cerebral vascular and metabolic effects of adding nitrous oxide to isoflurane from 1.4% expired (1 MAC) up to a concentration giving an isoelectric electroencephalogram (EEG). Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were determined using a sagittal sinus outflow technique. At 1.4% expired isoflurane, 70% nitrous oxide increased CBF but had no effect on CMRO2. At 3.1% expired isoflurane, 70% nitrous oxide had no effect on either CBF or CMRO2. The latter concentration of isoflurane rendered the EEG isoelectric, but when nitrous oxide was added, EEG activity reappeared. To again produce an isoelectric EEG required an increase in the isoflurane concentration to 3.5% +/- 0.2% (with no further effect on CMRO2). The authors also found that at 1.4% isoflurane, 0.9 micrograms.kg-1.min-1 of angiotensin significantly decreased CMRO2 without any effect on CBF. It is concluded that nitrous oxide, when added to isoflurane concentrations ranging from 1.4% to 3.5% in the dog, increases CBF at the low but not the high isoflurane concentrations although it has no effect on CMRO2.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours

In 10 patients subjected to craniotomy for supratentorial cerebral tumours in neurolept anaesthesia, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice peroperatively by a modification of the Kety & Schmidt technique, using 133Xe. The relative CO2 reactivity was assessed indirectly as the % change of the arteriovenous oxygen difference (AVDO2) per mm change in PaCO2. The patients were premedicated with diazepam 10-15 mg perorally. For induction, thiopentone 4-6 mg/kg, droperidol 0.2 mg/kg and fentanyl 5 micrograms/kg were used, and for maintenance N2O 67% and fentanyl 4 micrograms/kg/h. During the first flow measurement the median and range of CBF was 30 ml/100 g/min (range 17-45), of AVDO2 8.0 vol % (range 4.1-9.5), and of CMRO2 2.28 ml O2/100 g/min (range 1.57-2.84). During the second CBF study, AVDO2 increased to 9.3 vol % (range 3.4-11) (P less than 0.05), and CMRO2 increased to 2.51 ml O2/100 g/min (range 1.88-3.00) P less than 0.05, while CBF was unchanged. The CO2 reactivity was present in all studies, median 1.8%/mmHg (range 0.5-15.1). The correlation coefficients between jugular venous oxygen tension/saturation, respectively, and CBF were high at tensions/saturations exceeding 4.0 kPa and 55%, indicating that hyperperfusion is easily unveiled by venous samples from the jugular vein during this anaesthesia.     

Comparison of the effects of succinylcholine and atracurium on intracranial pressure in monkeys with intracranial hypertension

The effects of succinylcholine (1.5 mg X kg-1 IV) administered five minutes after a defasciculating dose of curare (0.05 mg X kg-1 IV), were compared with the effects of atracurium (0.5 mg X kg-1 IV) on intracranial pressure (ICP) in 13 cynomolgus monkeys with intracranial hypertension (ICP approximately 25 mmHg). Neither succinylcholine nor atracurium increased ICP during general anaesthesia with 60 per cent N2O/O2, 0.5-1 per cent halothane. During a rapid sequence induction and intubation with thiopentone 5 mg X kg-1 IV, ICP increased equally with intubation following both atracurium (25 +/- 1 to 32 +/- 2 mmHg) and succinylcholine (25 +/- 1 to 31 +/- 2 mmHg) (p less than 0.05). Intubation was also associated with significant increases in PaCO2, CVP and MAP. We conclude that in this primate model of intracranial hypertension, neither atracurium nor succinylcholine (when given following a defasciculating dose of curare) elevates ICP. In terms of the elevation of ICP associated with intubation, atracurium was found to offer no advantage over succinylcholine.     

Cerebral stimulation following succinylcholine in dogs

The effects of iv succinylcholine (SCh) on the electroencephalogram (EEG), cerebral blood flow (CBF), cerebral metabolic rate (CMRO2), intracranial pressure (ICP), central venous pressure (CVP), and mean arterial pressure (MAP) were tested in halothane-anesthetized dogs. Six dogs were maintained at 0.87 +/- 0.00% (mean +/- SE) expired halothane (1.0 MAC) and received both SCh 1.0 mg X kg-1 and lactated Ringer's solution placebo 0.05 ml X kg-1. Fasciculations began 24 +/- 4 s after iv SCh. Fasciculations were followed by immediate EEG arousal in five of six dogs and increases in CBF in all six. Average CBF was 151 +/- 14% of control for the 0-15 min measurement period and 127 +/- 7% of control for the 15-30 min period. Both were significantly greater than pre-SCh control values and placebo group values. Peak CBF of 177 +/- 19% of control occurred 3 min after iv SCh and was accompanied by a peak ICP of 435 +/- 131% of control. ICP values were significantly different between SCh and placebo treatments only during the periods of greatest CBF (1 to 5 min after iv SCh). Average PaCO2 values after iv SCh were significantly greater than pre-SCh control values and placebo values during each 15-min measurement interval. Average PaCO2 was 116 +/- 2% of control during the 0-15 min measurement period, 114 +/- 2% of control during the 15-30 min period, and 109 +/- 1% of control during the 30-45 min period. CVP, MAP, and CMRO2 did not significantly change after iv SCh.(ABSTRACT TRUNCATED AT 250 WORDS)     

CBF and CMRo2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

In 14 patients with supratentorial cerebral tumours with midline shift less than or equal to 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety & Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In Group 1 (n = 7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRO2 measured about 70 min after induction averaged 30.1 ml 100 g-1 min-1 and 1.98 ml O2 100 g-1 min-1, respectively. During the second CBF study 1 h later, CBF and CMRO2 were unchanged (P greater than 0.05). In Group 2 (n = 7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRO2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRO2 and suppression in the EEG activity, whereas CBF was unchanged.     

Alfentanil as an adjunct to thiopentone and nitrous oxide in short surgical procedures

Alfentanil, a new narcotic analgesic with a rapid onset and short duration of action was used as an adjunct to thiopentone and nitrous oxide anaesthesia in 109 patients undergoing dilatation and curettage (D&C) or therapeutic abortion (TA). The mean alfentanil dose was 19.7 +/- 9.6 microgram X kg-1 (D&C Group) and 23.3 +/- 6.6 micrograms X kg-1 (TA Group), with a mean duration of anaesthesia of about 30 minutes. The anaesthetic effect was judged excellent in virtually all patients (94.7 per cent in the TA group and 96.7 per cent in the D&C group). There were no significant changes in haemodynamic parameters intraoperatively. Apnea or hypoventilation was observed in four patients and was easily reversed by naloxone. Most patients (95.4 per cent) demonstrated complete recovery of consciousness, motor activity, respiratory and circulatory function and skin colour within 60 minutes of arrival in recovery room. The only consistent side effect was minor chest wall rigidity which was eliminated by pretreatment with d-tubocurarine. One patient experienced a serious adverse reaction which was reversed with naloxone. We have found alfentanil to be well suited as an adjunct to nitrous oxide and thiopentone in short surgical procedures.     

Disposition of propofol infusions for caesarean section

The disposition of propofol was studied in women undergoing elective Caesarean section. Indices of maternal recovery and neonatal assessment were correlated with venous concentrations of propofol. After induction of anaesthesia with propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr-1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/- 9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8-16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and 0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV concentrations of propofol at delivery had lower neurologic and adaptive capacity scores 15 minutes later. The concentrations of propofol were similar between groups during the infusion but they declined at a faster rate in the low group postoperatively. Maternal recovery times did not depend on the total dose of propofol but the concentration of propofol at the time of eye opening was greater in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32 micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol during Caesarean section requires propofol infusions to be given cautiously, especially when induction to delivery times are long.     

The effects of intravenous anaesthetic agents on human neutrophil chemiluminescence

Intact neutrophil function is essential for the defence against infection. Any alteration in neutrophil function, which decreases their ability to phagocytose and kill bacteria, might contribute to mortality and morbidity. We investigated the effects of clinical concentrations of thiopentone, Alfathesin, methohexitone, morphine, lidocaine and diazepam on the microbicidal oxidative function of human neutrophils. The oxidative activity was assessed utilizing the technique of chemiluminescence, which is a measure of free radical generation. Thiopentone and Alfathesin produced a significant dose dependent depression in chemiluminescence. There was a 27 per cent reduction in activity with thiopentone 5 micrograms X ml-1, a concentration equivalent to the free plasma concentration achieved following an anaesthetizing dose of thiopentone. There was a 55 per cent reduction in chemiluminescence at an alphaxolone concentration of 1.25 micrograms X ml-1, a concentration equivalent to the free plasma level obtained after induction of Alfathesin anaesthesia. The effect of thiopentone and Alfathesin was reversed by cell washing. Methohexitone, morphine, diazepam, and lidocaine caused no significant reduction in chemiluminescence over the dose ranges studied. These observations indicate that thiopentone and Alfathesin can adversely affect leucocyte function in vitro and, therefore, may contribute to impaired host resistance in the perioperative period and in the intensive care unit.     

Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs

The effects of a continuous infusion of etomidate on cerebral function, metabolism, and hemodynamics and on the systemic circulation were examined in six dogs. The infusion rate of etomidate was progressively increased at 20-min intervals from 0.02 to 0.4 mg X kg-1 X min-1 for 2 h. Cerebral oxygen consumption (CMRO2) decreased until there was cessation of neuronal function as reflected by the onset of an isoelectric EEG. This occurred during an infusion of 0.3 mg X kg-1 X min-1 etomidate when the animals had received a total of 10.7 mg X kg-1 over 91 min. At this time the CMRO2 was 2.6 ml X min-1 X 100 g-1, 48% of control. Thereafter, despite continued administration of etomidate to a total dose of 21.4 mg X kg-1, CMRO2 did not decrease further. Cerebral blood flow (CBF) decreased in association with a marked increase in cerebrovascular resistance but was independent of changes in CMRO2. CBF decreased precipitously from 145 +/- 23 to 72 +/- 6 ml X min-1 X 100 g-1 during the lowest infusion rate of 0.02 mg X kg-1 X min-1 etomidate and stabilized at 34-36 ml X min-1 X 100 g-1 during an infusion rate of 0.1 mg X kg-1 X min-1. CBF remained at this level despite the continued administration of etomidate and a further decrease in CMRO2. Etomidate produced physiologically minor but statistically significant changes in the systemic hemodynamic variables. Assays of cerebral metabolites taken at the end of the infusion revealed a normal energy state and a very mild but significant increase in cerebral lactate to 1.49 mumol X g-1. We conclude that etomidate is a potent, direct cerebral vasoconstrictor that appears to be independent of its effect on CMRO2 and that the cerebral metabolic effects of etomidate are secondary to its effect on neuronal function, with little if any direct or toxic effects on metabolic pathways.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2-reactivity during craniotomy for supratentorial cerebral tumours in halothane anaesthesia. A dose-response study

Fourteen patients were studied during craniotomy for small supratentorial cerebral tumours. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by a modification of the Kety-Schmidt technique using 133Xe intravenously. Anaesthesia was induced with thiopental 4-6 mg kg-1, fentanyl and pancuronium, and maintained with an inspiratory halothane concentration of 0.45% in nitrous oxide 67% at a moderate hypocapnic level. In one group of patients (n = 7) the inspiratory halothane concentration was maintained at 0.45% throughout anaesthesia. About 1 h after induction of anaesthesia CBF and CMRO2 averaged 35 +/- 2 ml 100 g-1 min-1 and 2.7 +/- 0.3 ml O2 100 g-1 min-1 (mean +/- s.c. mean), respectively. During repeat studies 1 h later CBF and CMRO2 did not change. In another group of patients (n = 7) an increase in halothane concentration from 0.45% to 0.90% was associated with a significant decrease in CMRO2 from 2.3 +/- 0.1 to 2.0 +/- 0.1 ml O2 100 g-1 min-1. The CO2-reactivity measured after the second flow measurement was preserved. It is concluded that halothane in this study induces a dose-dependent decrease in cerebral metabolism, an increase in CBF while CO2-reactivity is maintained.     

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.     

The effect of sufentanil on cerebral blood flow, cerebral metabolism and the CO2 reactivity of the cerebral vessels in man]

Sufentanil, a synthetic opioid that is 5-10 times as potent as fentanyl, has been suggested for use during neurosurgical procedures because it maintains cardiovascular stability and produces hypnosis without the use of additional anesthetic agents. Doses as low as 2.5 micrograms.kg-1 are reported to create deep levels of anesthesia as demonstrated by EEG changes to high-amplitude delta-waves. However, there are no reports concerning the effects of sufentanil on blood flow and metabolism in the human brain. The present study was designed to investigate the influence of high-dose sufentanil-O2 anesthesia on the cerebral circulation, metabolism, and the cerebrovascular response to CO2 in man. METHODS. Nine male and 2 female patients between 41 and 60 years of age who were scheduled for coronary artery bypass surgery were studied. Premedication consisted of flunitrazepam 2 mg orally and piritramide 15 mg and promethazine 50 mg i.m. 1 h before arrival in the induction room. Measurements were performed with the patients awake (I), after sufentanil 10 micrograms.kg-1 as an induction dose followed by 0.15 micrograms.kg-1.min-1 as an infusion with normocapnia (pa CO2 42.1 +/- 2 mmHg) (II), during hypercapnia (pa CO2 53.7 +/- 3.5 mmHg) (III), and during hypocapnia (pa CO2 31.7 +/- 2 mmHg) (IV). Cerebral blood flow (CBF) was measured using the argon wash-in technique. Cerebral venous blood was obtained from a catheter in the superior bulb of the right internal jugular vein. Cerebral metabolic rates of oxygen (CMRO2) glucose (Mgluc) lactate (CMlac) were calculated by multiplying the arterial-cerebral venous oxygen and substrate differences by CBF. The Anaerobic Index was calculated from the equation avD lactate x 100/2 x avD glucose = ANI (%) Cerebral electrical activity was recorded by aperiodic analysis of the EEG (Lifescan). RESULTS AND DISCUSSION. In the EEG sufentanil anesthesia was characterized by a decrease in the number of high-frequency waves and an increase in the number and amplitude of delta-waves, a pattern that did not change throughout the study period. Concomitantly, under normocapnic conditions high-dose sufentanil led to the significant decrease in CBF by 29% accompanied by an 18% increase in cerebral vascular resistance (CVR). CMRO2 decreased by 22% while CMRgluc and CMRlac changed only insignificantly such that the ANI, which represents the percentage of anaerobically metabolized glucose, essentially remained unchanged. Mean perfusion pressure declined by 18% but stayed within the range of autoregulation. Hypoventilation (III) was followed by an 82% increase in CBF as a result of a 55% reduction in CVR, whereas cerebral metabolic parameters did not show important changes when compared to measurement II. Hyperventilation (IV), on the other hand, produced a distinct fall in CBF by 56% to a value that was 21% below the one obtained under normocapnia. This was due to an increase in CVR of the same magnitude. There was a 31% rise in CMRO2, resulting in a decrease in cerebral venous oxygen tension, but in no case did it fall below the critical value of 20 mmHg at which tissue hypoxia becomes severe. Although CMRlac increased and CMRgluc did not significantly change, the ANI remained essentially unchanged, which suggests a predominantly aerobic metabolism. The increase in metabolic activity with sufentanil during hypocapnia might be caused by an alkalosis-induced stimulation of glycolysis. It might also be related to a reduction in the depth of anesthesia, although neither the EEG nor the hemodynamic parameters indicated this. This study shows that the coupling between CBF and metabolism is well maintained and that the cerebrovascular response to CO2 is unimpaired during high-dose sufentanil anesthesia.     

The effect of isoflurane on cerebral blood flow and metabolism in humans during craniotomy for small supratentorial cerebral tumors

Fourteen patients were studied during craniotomy for small supratentorial cerebral tumors. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by a modification of the Kety-Schmidt technique using 133Xe intravenously. Anesthesia was induced with thiopental 5-7 mg X kg-1, fentanyl 0.2 mg, and pancuronium, and maintained with 0.75% inspired isoflurane concentration in 67% nitrous oxide, and moderate hypocapnia. In one group of patients (n = 7), the inspired isoflurane concentration was maintained at 0.75% throughout anesthesia. One hour after induction of anesthesia, CBF and CMRO2 averaged 31 +/- 3 ml X 100 g-1 X min-1 and 2.1 +/- 0.2 ml O2 X 100 g-1 X min-1 (X +/- SEM), respectively. During repeat studies 1 h later, CBF and CMRO2 were unchanged. In a second group of patients (n = 7), an increase in the inspired isoflurane concentration from 0.75% to 1.5% was associated with a significant decrease in CMRO2 from 2.4 +/- 0.1 to 1.9 +/- 0.1 ml O2 X 100 g-1 X min-1, and no change in CBF. It is concluded that this anesthetic regimen is safe to use in patients with small supratentorial tumors in whom only a small midline shift has occurred.     

The detrimental effect of lidocaine on cerebral metabolism measured in dogs anesthetized with isoflurane

Previous studies in dogs have demonstrated that massive doses of intravenous lidocaine (160 mg X kg-1) can inhibit cerebral oxygen metabolism to a greater degree when administered with pentobarbital than can pentobarbital alone. From these data, it was hypothesized that lidocaine decreases cerebral metabolism by two means: suppression of cortical electrical activity and stabilization of neuronal membranes, and it was suggested that lidocaine might provide protection for the ischemic brain. In an attempt to apply this property clinically, the effect of a lower, clinically tolerated dose of lidocaine (15 mg X kg-1) on cerebral oxygen metabolism and cerebral blood flow was examined in dogs receiving deep isoflurane anesthesia. Once maximal metabolic suppression, as reflected by an isoelectric EEG, was achieved with isoflurane (3% end-expired), the administration of this dose of lidocaine had little effect on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). The CBF was 94 +/- 19 ml X min-1 X 100 g-1 during 3% isoflurane anesthesia, and was 102 +/- 11 ml X min-1 X 100 g-1 with the addition of lidocaine. The CMRO2 was 2.32 +/- 0.23 ml X min-1 X 100 g-1 during isoflurane anesthesia, and was 2.18 +/- 0.09 ml X min-1 X 100 g-1 following the administration of lidocaine. However, this dose of lidocaine did produce a derangement of cerebral metabolites. The cerebral concentration of ATP during 3% isoflurane anesthesia was 2.07 +/- 0.04 mumol X g-1 (cerebral ATP in normal unanesthetized dogs is 2.01 +/- 0.01 mumol X g-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thiopental bolus during carotid endarterectomy-rational drug therapy?

Ten studies were performed to examine the time course of arterial and venous thiopental concentrations following the administration of thiopental (4 mg X kg-1 over 3 min) for cerebral protection during carotid occlusion in nine patients undergoing elective carotid endarterectomy; in five patients the time course of EEG change was also studied. The arterial and venous thiopental concentrations were similar with no evidence of a sustained arterial-venous gradient. The average arterial concentration was 20.1 microgram X ml-1 +/- 10 (SD) at 2 min after thiopental, and fell rapidly to 13.0 micrograms X ml-1 +/- 3.2 at 5 min, 10.7 micrograms X ml-1 +/- 4.4 at 10 min and 6.2 micrograms X ml-1 at 30 min. After thiopental the EEG record showed an increase in delta activity and in four patients a burst suppression pattern was seen. The duration of burst suppression activity was variable (130 to 367 seconds) but in all instances cortical activity had returned to the pre-thiopental level by five to ten minutes. Thus concentrations of thiopental of 10-30 micrograms X ml-1 were associated with EEG burst suppression and both were seen only within the first five minutes after drug administration. In contrast the carotid artery was occluded for considerably longer (26 +/- 4) minutes. We conclude that, since there was no sustained arterial-venous gradient, either arterial or venous concentrations are adequate for the study of thiopental pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)