Closed-loop infusion of atracurium with four different anesthetic techniques

A new proportional-integral-derivative (PID) controller for the automated closed-loop delivery of atracurium was tested in 32 patients. Groups of 8 patients received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium 0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion calculated by the controller to maintain the electromyogram (EMG) at a setpoint of 90% neuromuscular blockade. The average overshoot for the controller was 10.1% and the mean steady-state error 3.0%. The mean infusion rates for atracurium to maintain 90% blockade were calculated for each anesthetic group, with the inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%, enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/- 0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/- SE). The infusion rate for atracurium at 90% blockade under N2O/morphine anesthesia was in general agreement with published values. The other infusion rates at 90% blockade have not been reported previously, but correspond to the known potencies of these inhalation anesthetics for augmentation of neuromuscular blockade. This controller performed well in comparison to previously developed controllers, and in addition was used as a research tool for rapid estimation of infusion rates.     

Atracurium infusion requirements in children during halothane, isoflurane, and narcotic anesthesia

We were interested in determining the dose-response relationship of atracurium in children (2-10 yr) during nitrous oxide-isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide-halothane (0.8%), nitrous oxide-isoflurane (1%), or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five children received 80, 100, 150 micrograms/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 micrograms/kg was 23.6% +/- 6.5 (mean +/- SEM), by 100 micrograms/kg was 45% +/- 7.2, and by 150 micrograms/kg was 64% +/- 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 micrograms/kg and 280 micrograms/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 +/- 0.6 micrograms . kg-1 . min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 +/- 0.8 micrograms . kg-1 . min-1 (P less than 0.05). There was no evidence of cumulation during prolonged atracurium infusion.     

Continuous infusions of atracurium and vecuronium,compared with intermittent boluses of pancuronium: dose requirements and reversal

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term succinylcholine infusion during isoflurane anesthesia

The characteristics of the neuromuscular blockade produced by prolonged succinylcholine infusion were compared in 40 patients anesthetized with either nitrous-oxide-isoflurane (0.75-1.50% inspired) or nitrous-oxide-fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15% of its control value. Initially, all patients exhibited a depolarizing-type block, and the infusion rates were similar in the isoflurane (61 micrograms . kg-1 . min-1) and fentanyl (57 micrograms . kg-1 . min-1) groups. Tachyphylaxis developed in both groups and correlated well with the onset of non-depolarizing (phase II) block. Both occurred sooner and at a lower cumulative dose in the isoflurane groups. After 90 min, infusion rates were similar in both groups (isoflurane: 107 micrograms . kg-1 . min-1, fentanyl;: 93 micrograms. kg-1 . min-1). After the infusion was stopped, the recovery of the train-of-four ratio was inversely related to the dose and duration of exposure to succinylcholine, and was slower with nitrous-oxide-isoflurane anesthesia. After 10 min of recovery, patients receiving isoflurane exhibited train-of-four ratios of 0.5 or less after 8.5 mg/kg succinylcholine and 103 min. Corresponding figures for fentanyl patients were 13 mg/kg and 171 min. The block in all 13 patients (eight with isoflurane, five with fentanyl) who did not recover spontaneously was antagonized successfully with atropine and neostigmine. It was concluded that with succinylcholine infusion of 90 min or less, isoflurane accelerates the onset of tachyphylaxis and phase II neuromuscular block without affecting succinylcholine requirements. These results, with isoflurane, were similar to those reported previously with enflurane or halothane.     

Amrinone reverses cardiac depression by enflurane in the dog]

To evaluate the interaction of amrinone with inhalational anesthetics, cardiovascular effects of amrinone were investigated in nine mongrel dogs anesthetized with enflurane. Each dog received enflurane and amrinone in the following sequence: 1) 2% enflurane alone, 2) continuous infusion of 20 micrograms.kg-1.min-1 during enflurane, 3) 40 micrograms.kg-1.min-1 infusion during enflurane. Amrinone 40 micrograms.kg-1.min-1 during enflurane anesthesia improved the maximum left ventricular dP/dt, stroke volume and decreased effective arterial elastance (Ea) without changes in left ventricular end-diastolic pressure and heart rate. Left ventricular pressure (LVP) and systolic femoral arterial pressure were stable, but diastolic femoral arterial pressure decreased significantly from enflurane anesthesia alone. These parameters at 20 micrograms.kg-1.min-1 of amrinone infusion during enflurane showed the same tendency with 40 micrograms.kg-1.min-1 infusion but not significantly different from enflurane alone. This result suggests that amrinone may be beneficial in the patients with depression of cardiac performance during anesthesia.     

Atracurium and vecuronium: repeated bolus injection versus infusion.

The purpose of this study was to compare the characteristics of recovery from neuromuscular blockade after either atracurium or vecuronium given by intravenous infusion or by repeated injection. Four groups of 10 patients each were studied during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95 of either muscle relaxant was followed by an intravenous infusion started at 5% recovery of control twitch tension and adjusted for 95% block or by repeated injection of 0.6 x ED95 administered whenever twitch tension had returned to 25% of control. There were no significant differences between the maintenance doses required based on method of administration: atracurium repeated injection, 1.6 +/- 0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h-1. Nevertheless, differences of up to 20 min were noted in the recovery indices in the following order: atracurium repeated injection = atracurium infusion less than vecuronium repeated injection less than vecuronium infusion. A single dose of neostigmine (7 micrograms/kg) significantly reduced the recovery indices, thereby eliminating their differences.     

Intubation with low-dose atracurium in children

The objective of this study was to compare intubating conditions and neuromuscular effects using smaller doses of atracurium (0.25 mg/kg and 0.3 mg/kg) with the recommended dose of 0.4 mg/kg for intubation in children anesthetized with halothane, N2O and oxygen undergoing strabismus repair. All patients (10 in each group) had good or excellent intubating conditions at 80% depression of twitch height [T1 of train-of-four (TOF) stimulation]. Mean times to intubation were 2.6 +/- 0.2 minutes following 0.25 mg/kg and 2.2 +/- 0.2 minutes following 0.3 mg/kg. These times were significantly longer (P less than 0.05) than the mean intubation time of 1.5 +/- 0.2 minutes following 0.4 mg/kg. Mean times to recovery, defined as times from injection of atracurium to return of T1 of TOF to 10%, 25%, and 95% of control measurements, were significantly shorter with the smaller doses. Atracurium at these low doses may provide an alternative to succinylcholine for intubating children during halothane anesthesia for surgical procedures lasting 20-30 min.     

Vecuronium infusion dose requirements during fentanyl and halothane anesthesia in humans

Steady-state infusion rate requirements of vecuronium were determined in 29 patients during either halothane-nitrous oxide or fentanyl-nitrous oxide anesthesia at different levels of neuromuscular block. During N2O-halothane anesthesia (end-tidal concentration, 0.5%), the infusion rate necessary for a steady-state (defined as unchanging twitch height and infusion rate for at least 20 min) 50% depression of twitch force was 28.8 +/- 5.4 (mean +/- SD) (n = 8) and 47.6 +/- 9.7 micrograms . kg-1 . hr-1 (n = 6) at 90% reduction of twitch force. During N2O-fentanyl anesthesia, the steady-state infusion rate required for 50 and 90% decrease of twitch force was 56.3 +/- 20.0 (n = 9) and 74.8 +/- 16.0 micrograms . kg-1 . hr-1 (n = 6), respectively. The variances of vecuronium steady-state infusion dose requirements were smaller in the halothane groups than in the fentanyl anesthesia groups. The steady-state vecuronium infusion dose requirements during fentanyl anesthesia were greater than the mean infusion dose requirements during halothane anesthesia at equivalent levels of twitch depression.     

Effects of halothane and fentanyl anesthesia on resistance to reabsorption of CSF

Using the technique of ventriculocisternal perfusion, resistance to reabsorption of cerebrospinal fluid (Ra) was examined in dogs during anesthesia with halothane (0.8%) or fentanyl (3.0 micrograms X kg-1 X min-1 for 20 minutes, followed by 0.2 micrograms X kg-1 X min-1, intravenously). Compared to normal Ra in dogs (220 to 224 cm H2O X ml-1 X min-1), halothane increased Ra to 245 +/- 2 cm H2O X ml-1 X min-1 (mean +/- standard error of the mean), and fentanyl decreased Ra to 114 +/- 1 cm H2O X ml-1 X min-1. Changes in Ra caused by halothane or fentanyl may contribute, in part, to changes in intracranial pressure (ICP) observed during prolonged anesthesia with these agents. Because decreased Ra improves spatial compensation by cerebrospinal fluid volume during increased ICP, fentanyl may be preferred over halothane in patients at risk because of increased ICP.     

Postsystolic shortening of canine left ventricle supplied by a stenotic coronary artery when nitrous oxide is added in the presence of narcotics

The effects of fentanyl and sufentanil with and without N2O on left ventricular myocardium supplied by a critically narrowed and a normal coronary artery were studied in 16 dogs. Regional ventricular function was measured by recording ventricular segment length with the use of ultrasonic length detectors in the left anterior descending (LAD) and the left circumflex (LC) coronary artery territories before and during critical stenosis of the LAD. Critical stenosis was documented by the absence of a hyperemic response following a 10-s total occlusion of the LAD. Hemodynamic variables (aortic flow and pressure, left ventricular pressure, heart rate, and coronary blood flow) were measured and the first derivative of left ventricular pressure (LVdP/dt) and coronary perfusion pressure derived. Eight dogs received fentanyl 100 micrograms X kg-1 followed by an infusion of 1 microgram X kg-1 X min-1 while ventilated with O2:N2 (1:2), and eight dogs received sufentanil 30 micrograms X kg-1 with an infusion of 0.3 micrograms X kg-1 X min-1. Replacement of N2 with N2O produced evidence of mild systolic myocardial depression but no dysfunction in either group. After application of the critical constriction, the addition of N2O rapidly produced evidence of dysfunction with significant postsystolic shortening only in the LAD territory. This was not accompanied by hypotension or a decrease in coronary flow and was not always reversible. Higher infusion rates of either narcotic (fentanyl 2 micrograms X kg-1 X min-1, 4 micrograms X kg-1 X min-1; sufentanil 0.6 micrograms X kg-1 X min-1, 1.2 micrograms X kg-1 X min-1) in the absence of N2O did not produce dysfunction but had no protective effect when N2O was added.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. V. Role of pharmacokinetics and the autonomic nervous system in the interactions between verapamil and inhalational anesthetics

To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 +/- 10, 82 +/- 6, 81 +/- 10, and 77 +/- 9 ng.ml-1, respectively). For the latter purpose, the infusion dose was 3 and 2 micrograms.kg-1.min-1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 micrograms.kg-1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 +/- 5 bpm) and PR interval (35 +/- 9 msec) and a decrease in mean arterial pressure (-5 +/- 2 mmHg) and dP/dt (-494 +/- 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg.kg-1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil--changes similar to those previously reported with inhalational anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of inhalational anesthetics on verapamil pharmacokinetics in dogs

Six dogs were chronically instrumented in order to collect aortic blood samples and record mean arterial pressure, cardiac output and heart rate. Each animal received verapamil 200 micrograms X kg-1 by 10-min intravenous infusions on four occasions in random sequence: awake, and during halothane 1.2%, enflurane 2.5%, and isoflurane 1.6% anesthesia. Rate of initial distribution of verapamil was reduced during anesthetic exposure. Verapamil intercompartmental clearance from the central compartment to the peripheral compartment was decreased during exposure to halothane and isoflurane, and tended to decrease during enflurane exposure as well. Verapamil terminal volume of distribution at steady-state was reduced by halothane, enflurane, and isoflurane exposure as compared with awake: 65 +/- 10, 80 +/- 9, and 93 +/- 191, respectively, versus 132 +/- 121 (mean +/- SEM; P less than 0.05). Verapamil total clearance was also reduced by halothane, enflurane, and isoflurane as compared with awake: 37 +/- 4, 39 +/- 2 and 41 +/- 31 X h-1, respectively, versus 64 +/- 71 X h-1 (P less than 0.05). Verapamil administered to awake animals resulted in a decrease from baseline in mean arterial pressure; 95 +/- 8 mmHg versus 108 +/- 4 mmHg (P less than 0.05): and an increase in cardiac output; 2.60 +/- 0.33 1 X min-1 versus 1.93 +/- 0.22 1 X min-1 (P less than 0.05). During halothane, enflurane, and isoflurane anesthesia, verapamil administration resulted in a similar decrease in mean arterial pressure; however cardiac output decreased, in contrast to the increase noted in awake animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular and cardiovascular effects of mivacurium in children

The neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) were evaluated in 90 children (2-12 yr) during N2O:O2 halothane or N2O:O2 narcotic anesthesia. Neuromuscular response was evaluated by recording the force of contraction of the adductor of the thumb during train-of-four stimulation at 0.1 Hz. The children were divided into two groups. Patients in group A (n = 45) were anesthetized with N2O:O2 and halothane (1% inspired) and patients in group B (n = 45) were anesthetized with N2O:O2 and fentanyl or morphine. Each group was further divided into five subgroups of nine children. Children in the first three sets of subgroups (A1-A3, B1-B3) received an initial dose of 0.02, 0.04, 0.05, 0.06 or 0.07 mg/kg mivacurium to determine dose response relationships under the different anesthetic regimens. The ED50 and ED95 neuromuscular blocking doses calculated from this single dose technique were 0.051 mg/kg and 0.095 mg/kg, respectively, in children anesthetized with halothane N2O:O2, and 0.059 mg/kg and 0.11 mg/kg in children anesthetized with N2O:O2 narcotic. The fourth subset of each group (A4 and B4) received 0.09 mg/kg and 0.11 mg/kg mivacurium, the estimated ED95 for each respectively. The last subsets (A5 and B5) received 0.2 mg/kg. This dose induced 100% depression of the twitch response in all 18 patients in 1.8 +/- 0.1 min, with recovery to 5%, 25%, and 95% of control occurring in 8.4 +/- 0.5, 11.2 +/- 0.6 and 18.4 +/- 1.6 min, respectively. The recovery indices for all patients were 4.6 +/- 0.6 min for 25-75% recovery and 9.7 +/- 1.3 min for 5-95% recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of halothane on critical levels of oxygen transport in the anesthetized newborn lamb

A critical level of oxygen transport has been defined as the level which is required to maintain tissue oxygen uptake (VO2). If halothane reduces the susceptibility to hypoxia, it should lower the critical levels of both O2 delivery (DO2) and arterial oxygen tension (pO2). To test this hypothesis, 12 newborn lambs were anesthetized with either fentanyl and pancuronium (control group) or fentanyl, pancuronium, and 1.1% (1 MAC) halothane (halothane group). Baseline measurements of hemoglobin, cardiac output (CO), arterial and mixed-venous pO2, and saturation were obtained on FIO2 1.0, and repeated with FIO2 .21, .15, and .10. O2 delivery (CO X CaO2) and O2 consumption were calculated from measured parameters. Critical levels were selected using a system of repetitive linear regression. Halothane decreased baseline O2 consumption (12.1 +/- 0.7 to 8.4 +/- 0.4 cc X kg-1 X min-1, x +/- SEM, P less than .001, unpaired t test), but caused similar reductions in cardiac output (235 +/- 15 to 132 +/- 15 cc X kg-1 X min-1, P less than .001) and O2 delivery (29.2 +/- 2.9 to 20.2 +/- 1.6 cc X kg-1 X min-1, P less than .05). Addition of halothane decreased the critical level of O2 delivery from 17.9 to 14.3 cc X kg-1 X min-1, but had no effect on the critical level of arterial pO2 (control group, 47 mmHg halothane, 46 mmHg). Peripheral oxygen utilization was mildly reduced during halothane anesthesia, as evidenced by a decrease in oxygen extraction (control group O2 extraction rate = 0.63; halothane group O2 extraction = 0.51, P less than .05, unpaired t test).(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).     

Cerebral blood flow and metabolism in patients undergoing anesthesia for carotid endarterectomy. A comparison of isoflurane, halothane, and fentanyl

The effects of isoflurane, halothane, and fentanyl on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during anesthesia prior to carotid endarterectomy were compared using the intravenous method of 133-Xenon CBF determination. Patients, mean (+/- SE) age 68 +/- 2, received either isoflurane (N = 16), 0.75% in O2 and N2O, 50:50; halothane (N = 11), 0.5% in O2 and N2O, 50:50; or fentanyl (N = 10), 5-6 micrograms/kg bolus and then 1-2 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 40:60. Measurements were made immediately before carotid occlusion. Mean (+/- SE) CBF (ml.100 g-1.min-1) was 23.9 +/- 2.1 for isoflurane, 33.8 +/- 4.8 for halothane, and 19.3 +/- 2.4 for fentanyl. CMRO2 (ml.100 g-1.min-1) was available from 22 patients and was 1.51 +/- 0.28 for isoflurane (N = 7), 1.45 +/- 0.24 for halothane (N = 6), and 1.49 +/- 0.21 for fentanyl (N = 9). Although CBF was greater during halothane than during isoflurane or fentanyl anesthesia (p less than 0.05), there were no demonstrable differences in CMRO2 among the 3 agents. We conclude that choice of anesthetic agent for cerebrovascular surgery with comparable anesthetic regimens should not be made on the basis of "metabolic suppression." During relatively light levels of anesthesia, vasoactive properties of anesthetics are more important than cerebral metabolic depression with respect to effects on the cerebral circulation.     

The neuromuscular response of infants to a continuous infusion of succinylcholine

The response of the adductor of the thumb to ulnar nerve stimulation (0.1 Hz) was evaluated during continuous infusion of succinylcholine (SCh) in 20 infants anesthetized with halothane (1%) and N2O2/O2. Train-of-four stimulation (2 Hz for 2 s) was used to differentiate between phase I and phase II block. Some infants were very resistant to the neuromuscular effects of SCh. These infants (Group 1) were younger in age, 57 +/- 15 days (mean +/- SE) and required 24.6 +/- 3.3 mg X kg-1h-1 SCh to achieve more than 90% depression of the twitch. Older infants (Group 2), 188 +/- 33 days, required significantly less (P less than 0.001) SCh (8.7 +/- 0.5 mg X kg-1h-1) to achieve the same degree of twitch suppression. Group 1 infants recovered from the effects of SCh very rapidly. After 10 mg/kg SCh, the train-of-four ratio in Group 1 infants recovered to 75% in 4.7 +/- 0.6 min, whereas it took 34 +/- 10 min in Group 2 infants (P less than 0.01). Tachyphylaxis developed in infants after 3.6 +/- 0.3 mg/kg (mean +/- SE) and phase II block after 5.3 +/- 0.7 mg/kg (P less than 0.05) SCh. Combining the data of infants with that of children from a previous study conducted in a similar fashion resulted in significant correlation (P less than 0.001) between the log age and SCh requirement. The rate of administration of a continuous infusion of SCh in infants should be based upon the response of infants and not on a fixed dose (mg X kg-1 X h-1).     

The enflurane sparing effect of sufentanil in dogs

There is a ceiling to the reduction of enflurane MAC by fentanyl in the dog. Sufentanil (SUF), a more potent narcotic, may be more efficacious in reducing enflurane MAC. To test this hypothesis, 25 mongrel dogs were studied in three groups. Group 1 (n = 8) received SUF in progressively increasing infusion rates from 0.005 micrograms . kg-1 . min-1 to a maximum of 1.215 micrograms . kg-1 . min-1. MAC was determined at stable SUF concentrations in plasma [SUF] during each infusion rate. Group 2 (n = 10) received SUF at a dose rate (0.007 micrograms . kg-1 . min-1) designed to produce approximately 35% MAC reduction, and MAC determinations were made at regular intervals over a mean infusion time of 7.6 +/- 0.43 h (mean +/- SEM). Group 3 (n = 7) received 1.215 micrograms . kg-1 . min-1 and were studied as in group 2 over an infusion time of 6.7 +/- 0.42 h. In group 1, the highest infusion rate (1.215 micrograms . kg-1 . min-1) produced [SUF] = 48 ng/ml and reduced MAC by 71 +/- 6%. This was not statistically different from the reduction which occurred at [SUF] = 0.92 ng/ml (57 +/- 7%; infusion rate 0.015 micrograms . kg-1 . min-1; P = 0.21). In group 2, the degree of MAC reduction achieved by stable [SUF] (0.54 +/- 0.08 ng/ml) declined over time (MAC reduction at start = 34 +/- 2% versus 18 +/- 4.0% at the end of the infusion; P = 0.001), suggesting the development of tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epinephrine-induced premature ventricular contractions and changes in arterial blood pressure and heart rate during I-653, isoflurane, and halothane anesthesia in swine

I653 is a new inhalation anesthetic having especially desirable recovery characteristics because of its very low blood and tissue solubility. Investigations of its cardiovascular and electroencephalographic effects have revealed actions similar to those of isoflurane. However, these studies did not evaluate the potential of I653 to predispose the heart to epinephrine-induced arrhythmias. In this investigation, we studied eight domestic swine to compare the effects of I653 with those of other anesthetics on the cardiac arrhythmogenic actions of intravenously infused epinephrine. I653, isoflurane, and halothane each were given, on separate days, at 0.7-0.8 and at 1.1-1.2 MAC. The rate of infusion of epinephrine needed to produce premature ventricular contractions (PVCs) when the animals were anesthetized with I653 (6.9 +/- 0.7 and 6.6 +/- 0.9 micrograms.kg-1.min-1 at 0.8 and 1.2 MAC) did not differ from that during isoflurane anesthesia (5.7 +/- 1.1 and 6.0 +/- 1.0 micrograms.kg-1.min-1 at 0.7 and 1.1 MAC), but was greater than that required during halothane anesthesia (1.3 +/- 0.2 and 1.1 +/- 0.3 micrograms.kg-1.min-1 at 0.7 and 1.1 MAC). Similar mean arterial blood pressures and heart rates resulted from like infusions of epinephrine during I653 and isoflurane anesthesia. PVCs occurred at lesser infusion rates of epinephrine and at lower mean arterial blood pressures and heart rates with halothane than with I653 or isoflurane. Anesthetic concentration, over the range studied, did not alter the infusion rate of epinephrine required to produce arrhythmias with any anesthetic. The authors conclude that I-653 and isoflurane have similar properties with respect to epinephrine-induced arrhythmias and increases in heart rate and arterial blood pressure.     

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)