Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy.

The usefulness of intravenous dexmedetomidine infusion for maintenance of anesthesia was studied in patients anesthetized with thiopental, fentanyl, nitrous oxide, and oxygen. Isoflurane was added as needed. The study was conducted in two parts, the first of which was an open dose-response study that comprised 14 women undergoing abdominal hysterectomy. After a suitable infusion regimen of dexmedetomidine was determined according to hemodynamic criteria, 20 patients were included in a double-blind, randomized placebo-controlled trial (10 receiving dexmedetomidine, 10 saline solution). Dexmedetomidine was administered as a two-step infusion to rapidly achieve a steady-state plasma concentration. The infusion was started with an initial dose given over 10 min before the induction of anesthesia; at induction the maintenance rate was begun and continued until closure of the abdominal fascia. The infusion regimens of dexmedetomidine tested in the dose-response study ranged from 120 ng.kg-1 x min-1, followed by 6 ng.kg-1 x min-1, to 270 + 13.5 ng.kg-1 x min-1. In the second part of the study, an initial infusion of 170 ng.kg-1 x min-1 was chosen, followed by 10 ng.kg-1 x min-1 for maintenance. Anesthesia was induced with thiopental (4.0 mg/kg) and maintained with isoflurane in 70% nitrous oxide and oxygen. Isoflurane was administered according to predetermined hemodynamic criteria. Dexmedetomidine infusion did not completely abolish the need for isoflurane but diminished its requirement by > 90% (P = 0.02). The heart rate response to endotracheal intubation was significantly blunted.     

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.     

Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia

The pharmacokinetic and pharmacodynamic properties of alfentanil were studied in 64 surgical patients. Alfentanil was administered as a loading infusion (25-130 micrograms/kg) followed by a maintenance infusion (0.25-1.3 micrograms X kg-1 X min-1) as part of a nitrous oxide-narcotic-muscle relaxant technique. Although alfentanil doses of at least 50 micrograms/kg (in combination with thiopental, 2 mg/kg) were required to prevent hemodynamic changes during intubation, apnea or chest wall rigidity frequently occurred with alfentanil loading infusions exceeding 75 micrograms/kg. The alfentanil clearance rate was significantly lower in patients with liver dysfunction (2.3 +/- 1.3 vs 4.2 +/- 2.0 ml X kg-1 X min-1, mean +/- SD). In addition, the patients who required opioid antagonists to reverse postoperative respiratory depression had lower clearance rates (1.5 +/- 0.7 vs 4.1 +/- 1.9 ml X kg-1 X min-1) and longer elimination half-life values (406 +/- 304 vs 87 +/- 53 min). For maintenance of hemodynamic stability during superficial and intraabdominal operations, alfentanil serum concentration-response curves revealed ED95 values exceeding 300 ng/ml and 400 ng/ml, respectively. Our study also demonstrated a wide range of clinical responses to fixed doses of alfentanil. At equivalent doses, some patients required supplemental anesthetics, whereas others required an opioid antagonist. Careful titration of the alfentanil maintenance infusion is recommended to minimize the possibility of postoperative respiratory depression.     

Hormonal changes induced by etomidate in children during the first 24 postoperative hours

The hormonal effects of an etomidate infusion were assessed postoperatively in children undergoing hypospadias or clubfoot repair. The study was carried out in 12 children, aged between 9 and 70 months, randomly assigned to two equal groups. The anaesthetic protocol was identical for all the children, consisting in a light general anaesthesia (halothane induction, intubation after 60 to 80 micrograms.kg-1 vecuronium) combined with lumbar epidural anaesthesia (initial dose of 0.75 ml.kg-1 bupivacaine with adrenaline, with repeat injections of half the previous dose when there was a change in the haemodynamic parameters suggesting inadequate analgesia). Anaesthetic maintenance was different in both groups: 1 to 1.5 vol% enflurane in a nitrous oxide-oxygen mixture (1/1 v/v) in the control group, and 16.8 +/- 3.0 mg.kg-1.min-1 etomidate infusion in the etomidate group. Venous blood samples were collected after induction of anesthesia (before starting the epidural anaesthesia and the etomidate infusion), at the end of surgery (H0), at the 3rd (H3), 6th (H6), 12th (H12) and 24th h (H24) following surgery. The following hormonal blood concentrations were measured: cortisol, 11 beta-desoxycortisol, aldosterone, 11 beta-desoxycorticosterone, dehydroepiandrosterone (DHA) and DHA sulphate (DHA-S). In the control group, cortisol and DHA-S concentrations decreased significantly at H0, aldosterone levels also being significantly lower at H24. In the etomidate group, cortisol concentrations remained significantly lower at H0, H3 and H6; aldosterone concentrations were also significantly lower than control values throughout the study period. There was an important prolonged rise in the concentrations of their precursors. DHA and DHA-S concentrations did not change in the etomidate group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrinological changes following etomidate, midazolam, or methohexital for minor surgery

Etomidate is known to inhibit adrenocorticosteroid synthesis. The extent and duration of the effects of etomidate (63 +/- 6.4 mg) on spontaneous and stimulated corticosteroid levels, as well as on plasma concentrations of ACTH, beta-endorphin, and catecholamines were examined and compared to those following administration of the new benzodiazepine, midazolam, or of methohexital. Twenty-nine healthy, young, male orthopedic patients were randomized into three groups receiving either etomidate/fentanyl (n = 12), midazolam/fentanyl (n = 8), or methohexital/fentanyl (n = 9). Etomidate caused cortisol levels to decrease from 12.5 +/- 1.2 micrograms/dl preoperatively to 5.9 +/- 0.8 micrograms/dl after operation (P less than 0.001), compared to an increase from 12.0 +/- 1.9 micrograms/dl to 18.5 +/- 2.9 micrograms/dl in the group receiving methohexital. At 6 and 20 h postoperatively, all cortisol levels were normal. The cortisol decrease from 12.5 +/- 1.7 to 7.6 +/- 1.5 caused by midazolam was similar to that following etomidate, but the response to exogenous ACTH was significantly impaired in patients receiving etomidate as compared to those receiving midazolam. ACTH and beta-endorphin levels increased in patients receiving etomidate, presumably as a result of the interruption of negative feedback due to cortisol synthesis inhibition. Midazolam on the other hand prevented the increase of ACTH and beta-endorphin levels. Etomidate completely suppressed spontaneous aldosterone levels (from 33 +/- 6.7 to 7 +/- 2.1 pg/ml), as well as the response to stimulation with exogenous ACTH without affecting serum electrolytes. Etomidate had no influence on plasma catecholamines, but midazolam attenuated the stress-related epinephrine increase.     

Myocardial sensitization by thiopental to arrhythmogenic action of epinephrine in dogs

This study examined the interaction between thiopental and epinephrine in inducing ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with either halothane alone, thiopental alone, etomidate plus different doses of thiopental, or halothane plus different doses of thiopental. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during thiopental anesthesia (plasma thiopental concentration: 46-57 micrograms/ml) were 0.77 +/- 0.04 micrograms.kg-1.min-1 and 10.7 +/- 1.5 ng/ml, respectively. During halothane anesthesia (end-tidal: 1.3 MAC) they were 2.59 +/- 0.49 micrograms.kg-1.min-1 and 45.3 +/- 9.2 ng/ml, respectively. The dose-effect relationship for the thiopental action was examined during etomidate plus thiopental and halothane plus thiopental anesthesia. The arrhythmogenic plasma concentration of epinephrine was inversely proportional to the plasma thiopental concentration during both anesthetics. During etomidate plus thiopental anesthesia, at plasma thiopental concentrations of 0, 11.2 +/- 0.83, 20.1 +/- 1.34, and 33.2 +/- 1.95 micrograms/ml, the corresponding epinephrine concentrations were 201.3 +/- 34.3, 142 +/- 19.5, 69.1 +/- 21.2, and 22.7 +/- 4.5 ng/ml. During halothane plus thiopental anesthesia, at plasma thiopental concentrations of 0, 10 +/- 0.86, 18.3 +/- 0.87, and 31.8 +/- 1.05 micrograms/ml, the corresponding epinephrine concentrations were 45.3 +/- 9.2, 34.6 +/- 8.9, 16.2 +/- 1.74, and 15.1 +/- 1.32 micrograms/ml, respectively. These results suggest that thiopental sensitizes the heart to epinephrine in a dose-dependent manner. This sensitizing action of thiopental would in part explain the thiopental potentiation of hydrocarbon anesthetic-epinephrine arrhythmias.     

Pharmacokinetics of continuous infusion of etomidate in cirrhotic patients]

The pharmacokinetics of etomidate were studied in 9 control subjects (with normal liver function) and in 5 patients with cirrhosis scheduled for gastro-intestinal surgery. Anaesthetic induction included an initial bolus of etomidate 0.3 mg.kg-1, together with fentanyl 2 micrograms.kg-1, and pancuronium 60 micrograms.kg-1. An etomidate infusion was then started according to one of two following schemes: a (0.03 mg.kg-1.min-1 for 10 min, and then 0.01 mg.kg-1.min-1), or B (0.1 mg.kg-1.min-1 for 10 min, followed by 0.02 mg.kg-1.min-1 for a further 110 min, and 0.01 mg.kg-1.min-1 thereafter). Plasma concentrations of etomidate were determined at regular intervals throughout anaesthesia, and up to four hours afterwards, using inverse phase high pressure liquid chromatography. The infusion was given for 273 +/- 87 min in controls, and for 259 +/- 56 min in the cirrhotic group. Scheme A, only used in 3 controls and 1 cirrhotic in a preliminary study, resulted in very low plasma concentrations: 0.2 to 0.4 micrograms.ml-1. Those measured during the apparent plateau phase (steady state) of infusion protocol B were close to predicted values (0.5 to 0.6 micrograms.ml-1) in controls, whereas higher concentrations (approximately 1.5 micrograms.ml-1) were reached in cirrhotic patients. For all the patients the time interval to spontaneous recovery was 41 +/- 27 min; plasma levels were then 0.199 +/- 0.092 micrograms.ml-1. There were significant alterations in pharmacokinetic parameters in the cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Captopril reduces the dose requirement for sodium nitroprusside induced hypotension

The authors studied 12 patients who required deliberate hypotension for spinal fusion operations in order to investigate the efficacy of captopril for reducing dose requirement for sodium nitroprusside (SNP). Six patients, selected at random, were pretreated with captopril, 3 mg/kg po, and the remaining six patients served as controls. All patients received a similar anesthetic technique, consisting of thiopental 3 mg/kg, pancuronium 0.1 mg/kg, morphine 0.5 mg/kg, plus nitrous oxide 70% in oxygen. SNP was used to maintain mean arterial pressure (MAP) at 50-55 mmHg during deliberate hypotension lasting 140 +/- 13 minutes (mean +/- SE). Patients who received captopril required less SNP than untreated patients both early during hypotension (1.4 +/- 0.5 micrograms X kg-1 X min-1 vs. 4.8 +/- 0.8 micrograms X kg-1 X min-1, P less than 0.05), as well as late during hypotension (2.2 +/- 0.2 micrograms X kg-1 X min-1 vs. 5.6 +/- 0.6 micrograms X kg-1 X min-1, P less than 0.05). Whole blood cyanide was significantly lower in the patients pretreated with captopril than the untreated controls both early in the hypotensive period (2.7 +/- 0.6 mumol/l vs. 13 +/- 4 mumol/l, P less than 0.05) and also late in the hypotensive period (3.7 +/- 0.8 mumol/l vs. 30 +/- 10 mumol/l, P less than 0.05). MAP was reduced by captopril pretreatment both following induction of anesthesia (64 +/- 4 mmHg captopril vs. 80 +/- 4 mmHg control, P less than 0.05) and during surgery before deliberate hypotension (86 +/- 5 mmHg captopril vs. 100 +/- 4 control, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo regulation of non-insulin-mediated and insulin-mediated glucose uptake by cortisol

In vivo glucose uptake (Rd) occurs via two mechanisms: insulin-mediated glucose uptake (IMGU), which occurs in insulin-sensitive tissues, and non-insulin-mediated glucose uptake (NIMGU), which occurs in both insulin-sensitive and non-insulin-sensitive tissues. To determine whether these two pathways for in vivo glucose disposal are regulated independently, we studied the effect of stress levels of cortisol on IMGU and NIMGU in seven normal subjects after an overnight fast. To study NIMGU, somatostatin (SRIF, 600 micrograms/h) was infused to suppress endogenous insulin secretion and create severe insulinopenia, and glucose turnover was measured isotopically while serum glucose was clamped at approximately 200 mg/dl for 240 min. Separate studies were performed during the overnight infusion of saline or hydrocortisone (HCT; 2.0 micrograms.kg-1.min-1). The final 120 min of each study were used for data analysis. Under these conditions, insulin action is absent, and Rd = NIMGU. NIMGU was 204 +/- 11 mg/min and 208 +/- 8 mg/dl during saline and HCT, respectively (P NS). Therefore, HCT did not modulate NIMGU. To measure the effect of cortisol on Rd, hyperglycemic (200 mg/dl)-hyperinsulinemic clamp studies (30 mU.m-2. min-1) were performed during the infusion of saline or HCT. The results demonstrate that during saline infusion, steady-state rates of Rd (10.4 +/- 0.8 mg.kg-1.min-1) were achieved by 160 min; in contrast, during HCT infusion, Rd never reached steady state but increased from 4.5 +/- 0.2 in the 2nd h to 7.6 +/- 0.4 mg.kg-1.min-1 in the 4th h, P less than .01.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhancement by propofol of epinephrine-induced arrhythmias in dogs.

Although propofol is a widely used intravenous anesthetic, its effect on epinephrine-induced arrhythmias remains unknown. This study examined the possible interaction between propofol and epinephrine that might affect the induction of ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with halothane alone, propofol alone, etomidate alone, or etomidate plus varying doses of propofol. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during propofol anesthesia (blood propofol concentration 18.0 +/- 0.98 micrograms/ml) were 2.52 +/- 0.43 micrograms.kg-1.min-1 and 23.6 +/- 8.5 ng/ml, respectively. During halothane anesthesia (end-tidal 1.3 MAC), they were 2.66 +/- 0.21 micrograms.kg-1.min-1 and 35.7 +/- 1.9 ng/ml, respectively. During etomidate anesthesia, they were 9.67 +/- 1.06 micrograms.kg-1.min-1 and 205 +/- 27.5 ng/ml, respectively. The dose-effect relationship for propofol was examined during etomidate plus propofol anesthesia. Propofol reduced the arrhythmogenic plasma concentration of epinephrine in a concentration-dependent manner: at blood propofol concentrations of 2.33 +/- 0.46, 5.46 +/- 0.71, and 11.2 +/- 0.81 micrograms/ml, the corresponding plasma epinephrine concentrations were 182.6 +/- 52.5, 89.0 +/- 28.8, and 26.6 +/- 6.9 ng/ml, respectively. These results suggest that propofol enhances epinephrine-induced arrhythmias in a dose-dependent manner in dogs.     

Esmolol for potentiation of nitroprusside-induced hypotension: impact on the cardiovascular, adrenergic, and renin-angiotensin systems in man

Esmolol infusion at rates of 200, 300, and 400 micrograms.kg-1.min-1 was used to potentiate hypotension (mean arterial pressure = 60 mm Hg) induced with sodium nitroprusside (SNP) in 10 male patients undergoing radical cancer surgery during nitrous oxide-oxygen and fentanyl anesthesia. Heart rate (HR), blood pressure (radial arterial catheter), and plasma levels of renin activity (PRA), norepinephrine (N), epinephrine (E), and dopamine (D) were measured: 1) while patients were awake; 2) after induction of anesthesia (nitrous oxide, 60% in oxygen, fentanyl = 5 micrograms/kg followed by an infusion at 10 micrograms.kg-1.hr-1); 3) after surgery had begun; 4) after 20 minutes of SNP-induced hypotension; 5) after 20 minutes of esmolol at each of the above infusion rates; and 6) after the completion of surgery. Compared to awake values, SNP-induced hypotension (mean infusion rate = 3.1 micrograms.kg-1.min-1 +/- 0.6 SE) during surgery resulted in significant (P less than 0.05) increases in heart rate, PRA, N, and D. Infusion of esmolol resulted in significant (P less than 0.05) dose-dependent reductions in SNP requirement to maintain MAP = 60 mm Hg. At 200 micrograms.kg-1.min-1, SNP requirement was 2.1 micrograms.kg-1.min-1 +/- 0.4, at 300 micrograms.kg-1.min-1, it was 1.0 micrograms.kg-1.min-1 +/- 0.2, and at 400 micrograms.kg-1.min-1, was 0.5 micrograms.kg-1.min-1 +/- 0.3. Concomitant with the decrease in SNP requirement, there were significant reductions in HR and PRA at all infusion rates of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of remifentanil and fentanyl in patients undergoing carotid endarterectomy

BACKGROUND AND AIM: We investigated the haemodynamic stability and emergence characteristics of isoflurane/nitrous oxide anaesthesia supplemented with remifentanil or fentanyl in patients undergoing carotid endarterectomy. METHODS: Anaesthesia was induced with propofol (1-2 mg kg-1) and either remifentanil (0.5 microgram kg-1) or fentanyl (1 microgram kg-1), followed by an infusion of remifentanil (0.2 microgram kg-1 min-1) or fentanyl (2 micrograms kg-1 h-1). RESULTS: There were no significant differences between the groups in haemodynamic variables, postoperative pain, nausea or vomiting. After induction there was a significant decrease in mean arterial pressure for both groups (P < 0.001) and a decrease in heart rate (P = 0.001) in the remifentanil group. In both groups these haemodynamic changes continued during maintenance of anaesthesia (P < 0.05). The time to eye opening after surgery was significantly shorter with remifentanil compared with fentanyl (6.62 +/- 3.89 vs. 18.0 +/- 15.18 min, P = 0.015). CONCLUSION: Remifentanil appears to be a comparable opioid to fentanyl when supplementing isoflurane/nitrous oxide anaesthesia for carotid endarterectomy.     

Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--7. Effects on natural killer cell activity

Twenty four patients who underwent ophthalmic surgery were studied to evaluate activities of natural killer (NK) cells during and following total intravenous anesthesia with droperidol, fentanyl and ketamine. They were divided into three equal groups according to anesthetic methods employed. In enflurane group, anesthesia was induced with thiopental 5 mg.kg-1 and succinylcholine 1 mg.kg-1, and maintained with 1-2% enflurane, nitrous oxide (50%) and oxygen (50%). In original NLA group, anesthesia was induced as above and maintained with droperidol 0.15 mg.kg-1, fentanyl 5-10 micrograms.kg-1, nitrous oxide (70%) and oxygen (30%). The patients of total intravenous anesthesia group received droperidol 0.15 mg.kg-1, ketamine 2 mg.kg-1 and succinyl-choline 1 mg.kg-1 for induction of anesthesia, and then were given fentanyl 5-15 micrograms.kg-1, ketamine 2 mg.kg-1.hr-1 and oxygen (30%) for the maintenance of anesthesia. Vecuronium was given to every patient of the three groups for intraoperative muscle relaxation. Hartmann's solution was used at a speed of 5 ml.kg-1.hr-1. Peripheral venous blood 10 ml was drawn on six occasions during and after the surgery for the measurement of NK cell activities and endocrine response as judged by plasma catecholamine and cortisol levels. NK cell activities decreased significantly on the first post-operative day in enflurane group, but no significant differences were found among three groups in NK cell activities. The data suggest that inhaled anesthetics should not be easily employed for patients with depressed immune response, malignant disease and prolonged surgery.     

Continuous intravenous anesthesia with etomidate for carbon dioxide laser surgery of the larynx

Twenty-five adult patients undergoing carbon dioxide laser surgery for benign and malignant disease of the larynx were given continuous infusion of etomidate at 60 micrograms . kg-1 . min-1 for induction of anesthesia. Maintenance anesthesia was continued using one of three infusion rates: 20 micrograms . kg-1 . min-1 (n = 5), 30 micrograms . kg-1 . min-1 (n = 10), and 40 micrograms . kg-1 . min-1 (n = 10) of etomidate in air-oxygen mixture. Muscular relaxation was achieved by continuous infusion of succinylcholine, and fentanyl was used for analgesia. Continuous etomidate infusion for induction of anesthesia resulted in a significant decrease in the incidence of pain along the injection site to 8% and involuntary muscular movements to 12% compared with 35% and 44%, respectively, in a group of 25 adult patients undergoing endoscopic procedure who received intravenously a single volus injection of etomidate (0.3 mg .g kg-1). However, a prolonged recovery time was observed after 30 minutes of continuous etomidate infusion.     

Relation of the inhibition of cortisol synthesis in vivo to plasma etomidate concentrations

Young, healthy male patients undergoing body surface surgery under fentanyl-nitrous oxide-oxygen anesthesia were given an etomidate bolus for induction (0.3 mg/kg body weight) followed by a continuous infusion (0.36 mg.kg-1.h-1). The total etomidate dose was 63 +/- 6.4 mg (mean +/- standard error). Basal cortisol levels as well as the adrenocortical response to exogenous synthetic ACTH1-24 (0.25 mg i.m.) were determined preoperatively, at the end of anesthesia, and 6 and 20 h postoperatively. The reduction of the response to ACTH stimulation measured postoperatively as compared to preoperatively was calculated as percentage of the preoperative response. Plasma concentrations of etomidate were measured at the same sample times by gas chromatography. At the end of anesthesia the plasma level was 570 +/- 131 nM (mean +/- standard error). It decreased to 99 +/- 23 nM 6 h later and to 43 +/- 3 nM 20 h postoperatively. The plasma concentrations were plotted against the inhibition data. We found a sigmoid relationship between the relative inhibition and the log of the etomidate concentrations. We determined an EC50 for inhibition of 110 nM that agrees well with published data. We also found that the cortisol response was not completely suppressed at the concentrations measured here. This supports the results of a previous study in which we found that patients undergoing cardiovascular surgery still exhibited intra- and postoperative cortisol increases although they had been given large doses of etomidate. We conclude that the suppression of corticosteroid synthesis caused by etomidate is concentration-dependent. The suppression is negligible at concentrations lower than 40 nM.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Fentanyl-oxygen versus fentanyl-N2O/oxygen anaesthesia in children undergoing cardiac surgery

Fentanyl-oxygen (fentanyl-O2) anaesthesia was compared to fentanyl-nitrous oxide/oxygen (fentanyl-N2O/O2) anaesthesia in 14 children undergoing cardiac surgery. Children were randomly assigned to one of the two techniques studied, with seven patients in each group. The mean age (mean +/- SE) was 3.9 +/- 0.75 years (0.5-8.25 years) and mean weight 14.7 +/- 2 kg (3.5-29.5 kg). Patients were premedicated with IM atropine 0.02 mg . kg-1 and morphine 0.2 mg . kg-1 1 hour preoperatively. They received a fentanyl bolus of 30 micrograms . kg-1 with a concomitant continuous infusion of 0.3 micrograms . kg-1 . min-1. Pancuronium 0.1 mg . kg-1 was administered immediately following the fentanyl bolus. Fifty per cent nitrous oxide was given with oxygen in one group and 100 per cent oxygen was administered to the other group. Fentanyl plasma concentrations were similar in the two groups at the various stages of surgery. There were no significant differences between the two treatment groups in systolic and diastolic blood pressure or in heart rate in response to induction, intubation, and incision. There was a significantly greater increase in systolic blood pressure after sternotomy in the fentanyl-O2 group. In addition, in six of seven patients receiving fentanyl-O2 there were events of sudden increase in blood pressure during various stages of surgery before the bypass, necessitating an additional fentanyl bolus or the addition of droperidol in four cases. Similar phenomena were not documented in the fentanyl-N2O/O2 group. Our studies suggest that fentanyl-O2 anaesthesia in the schedule described, in children undergoing elective cardiac surgery for Tetralogy of Fallot, A-V canal, and transposition of the great arteries, is not sufficient to prevent elevation in systolic blood pressure despite fentanyl plasma concentrations in excess of 20 ng X ml-1. The addition of nitrous oxide prevents this phenomenon.     

Sevoflurane with continuous epidural anesthesia for removal of pheochromocytoma

A 66-year-old female was scheduled for right adrenalectomy because of a pheochromocytoma. Preoperative blood pressure was well controlled with an alpha.beta blocker, amosulalol hydrochloride 40 mg per day po for 2 weeks. The patient received midazolam 2.5 mg im and scopolamine 0.4 mg im 60 minutes before induction. Anesthesia was induced with midazolam 5 mg iv, fentanyl 0.1 mg iv and vecuronium 12 mg iv, and maintained with continuous epidural infusion of 1.5% lidocaine, and inhalation of 66% nitrous oxide in oxygen and sevoflurane (0.5-3%). Blood pressure was controlled with nicardipine (1-6 micrograms.kg-1.min-1) before removal of the pheochromocytoma. After removal of the tumor blood pressure was maintained with intravenous infusion of lactated Ringer's solution, dopamine (3-8 micrograms.kg-1.min-1), dobutamine (3-8 micrograms.kg-1.min-1) and norepinephrine (0.1-0.2 micrograms.kg-1.min-1). A combination of continuous epidural block and sevoflurane anesthesia was very useful for removal of the pheochromocytoma. Swan-Ganz catheter monitoring was also very useful before and during operation to determine the optimal doses of nicardipine, catecholamine and the volume of transfusion.     

Stimulation of lipolysis in humans by physiological hypercortisolemia

The effect of glucocorticoids on adipose tissue lipolysis in animals and humans is controversial. To determine whether a physiological increase in plasma cortisol, similar to that observed in diabetic ketoacidosis and other stress conditions, stimulates lipolysis, palmitate kinetics were measured in seven nondiabetic volunteers on two occasions with [1-14C]palmitate as a tracer. Subjects received a 6-h infusion of either 2 micrograms.kg-1.min-1 hydrocortisone or saline in random order. On both occasions, a pancreatic clamp (0.12 micrograms.kg-1.min-1 somatostatin, 0.05 mU.kg-1.min-1 insulin, and 3 ng.kg-1.min-1 growth hormone) was used to maintain plasma hormone concentrations at desired levels. Plasma cortisol concentrations increased to approximately 970 nM during cortisol infusion. Palmitate rate of appearance (Ra) and concentration increased by approximately 60% during cortisol infusion but did not change during saline infusion. Increments in palmitate Ra and concentration over the 6-h study were significantly greater during cortisol than saline infusion when compared by area-under-the-curve analysis (152 +/- 52 vs. -48 +/- 23 mumol.kg-1 and 12.2 +/- 4.1 vs. -4.9 +/- 4.1 mmol.min-1.L-1, respectively; P less than 0.02). Plasma glucose concentrations did not change significantly during cortisol (5.0 +/- 0.3 vs. 6.1 +/- 0.6 mM, NS) or saline (4.9 +/- 0.2 vs. 4.9 +/- 0.1 mM, NS) infusion. In nondiabetic volunteers, a 6-h cortisol infusion was associated with a 60% increase in palmitate Ra that did not occur with saline infusion. Thus, physiological hypercortisolemia may contribute to the increased rates of lipolysis observed in humans during stress.     

Effect of etomidate and thiopental on the onset of rocuronium action]

HYPOTHESIS: Differences in the hemodynamic effects of induction agents may cause them to affect the onset of action of rocuronium differently. OBJECTIVES: To compare the onset of action of rocuronium after induction with etomidate and thiopental. PATIENTS AND METHODS: Forty adult ASA I patients received 3 micrograms.kg-1. Three minutes later anesthesia was induced randomly with either 5 mg.kg-1 of thiopental (group I, n = 20) or 0.3 mg.kg-1 of etomidate (group II, n = 20). Rocuronium 0.6 mg.kg-1 was administered over 5 s. Baseline blood pressure and heart rate were measured just before delivery of rocuronium and just before intubation. Onset of action was defined as the time from injection of rocuronium until achievement of a blockade > or = 95% of the first electromyographic response in a trian-of-four stimulus of the short adductor of the thumb. We also studied intubation conditions. RESULTS: Etomidate was associated with a smaller decrease in systolic arterial pressure than was thiopental. Onset of action was 81 +/- 29 s in group I versus 72 +/- 23 s in group II (NS). Similar intubation conditions were observed in both groups. CONCLUSIONS: These results suggest that the induction drug does not affect rocuronium's onset of action.