The influence of renal function on the pharmacokinetics and pharmacodynamics and simulated time course of doxacurium.

UNLABELLED: Doxacurium's clearance (C1) is markedly decreased in patients with renal failure undergoing kidney transplantation. However, no studies have determined the influence of renal function (as assessed by creatinine clearance [CrCl]) on its pharmacokinetics in patients without renal failure. We studied 53 patients aged 19-59 yr. During N2O/isoflurane anesthesia, doxacurium was infused over 10 min, plasma was sampled for up to 6 h, and twitch tension was measured. A three-compartment model was fit to plasma concentration data and an effect compartment model to twitch data. Mixed-effects modeling was used to determine the influence of covariates, including CrC1, on doxacurium's pharmacokinetic/pharmacodynamic parameters. Obesity decreased both doxacurium's Cl (1.1% per percent above ideal body weight [IBW]) and its neuromuscular junction sensitivity (0.4% per percent above IBW). Cl increased 0.6% per mL/min increase in CrCl. In addition, the rate constant for equilibration between plasma concentration and effect decreased 46% per 1% increase in isoflurane, central compartment volume decreased 86% per 1% increase in isoflurane concentration, and slow distributional Cl decreased 69% per mg/ 100 mL increase in serum albumin. Simulations showed that the latter two covariates influence the time course of bolus doxacurium administration minimally. Both obesity and renal dysfunction prolong doxacurium's recovery markedly. When dosing is based on IBW, effects of CrCl on neuromuscular recovery are smaller compared with dosing based on actual weight. Therefore, obese patients should be dosed based on IBW. No further dosage adjustment is necessary for patients with renal dysfunction; however, recovery will take longer in patients with moderate-to-severe renal dysfunction. IMPLICATIONS: We examined the factors influencing doxacurium's pharmacokinetic and pharmacodynamic characteristics. Both creatinine clearance and obesity significantly influence its time course. The effect of obesity is minimized if patients are dosed based on ideal body weight.

Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions.

BACKGROUND: Remifentanil hydrochloride is an ultra-short-acting, esterase-metabolized mu-opioid receptor agonist. This study compared the use of remifentanil or fentanyl during elective supratentorial craniotomy for space-occupying lesions. METHODS: Sixty-three adults gave written informed consent for this prospective, randomized, double-blind, multiple-center trial. Anesthesia was induced with thiopental, pancuronium, nitrous oxide/oxygen, and fentanyl (n = 32; 2 micrograms.kg.-1. min-1) or remifentanil (n = 31; 1 mu.kg-1.min-1). After tracheal intubation, infusion rates were reduced to 0.03 microgram.kg-1.min-1 (fentanyl) or 0.2 microgram.kg-1.min-1 (remifentanil) and then adjusted to maintain anesthesia and stable hemodynamics. Isoflurane was given only after specified infusion rate increases had occurred. At the time of the first burr hole, intracranial pressure was measured in a subset of patients. At bone flap replacement either saline (fentanyl group) or remifentanil (approximately 0.2 microgram.kg-1.min-1) were infused until dressing completion. Hemodynamics and time to recovery were monitored for 60 min. Analgesic requirements and nausea and vomiting were observed for 24 h. Neurological examinations were performed before operation and on postoperative days 1 and 7. RESULTS: Induction hemodynamics were similar. Systolic blood pressure was greater in the patients receiving fentanyl after tracheal intubation (fentanyl = 127 +/- 18 mmHg; remifentanil = 113 +/- 18 mmHg; P = 0.004). Intracranial pressure (fentanyl = 14 +/- 13 mmHg; remifentanil = 13 +/- 10 mmHg) and cerebral perfusion pressure (fentanyl = 76 +/- 19 mmHg; remifentanil = 78 +/- 14 mmHg) were similar. Isoflurane use was greater in the patients who received fentanyl. Median time to tracheal extubation was similar (fentanyl = 4 min: range = -1 to 40 min; remifentanil = 5 min: range = 1 to 15 min). Seven patients receiving fentanyl and none receiving remifentanil required naloxone. Postoperative systolic blood pressure was greater (fentanyl = 134 +/- 16 mmHg; remifentanil = 147 +/- 15 mmHg; P = 0.001) and analgesics were required earlier in patients receiving remifentanil. Incidences of nausea and vomiting were similar. CONCLUSIONS: Remifentanil appears to be a reasonable alternative to fentanyl during elective supratentorial craniotomy.

A comparison of the effect of halothane on N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated excitatory synaptic transmission in the hippocampus.

Halothane depresses synaptic transmission in the rat brain. First we determined the concentration of halothane which decreased the amplitude of the population spike recorded in the CA1 region of the hippocampus to 50% of the control value (105 +/- 4.9 micrograms/mL [0.53 mM] halothane). Hippocampal glutamate receptors are divided into N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) and kainate (non-NMDA) subtypes. The NMDA and non-NMDA receptors were blocked with (+/-)-2-amino-5-phosphonopentanoic acid (AP5) (30 microM), and 6,7-dinitroquinoxaline-2,3-dione (DNQX) (10 microM), respectively, to allow observation of the effects of halothane on the NMDA and non-NMDA receptors, respectively. gamma-Aminobutyric acid type A (GABAA) receptors were blocked in all studies with picrotoxin (PTX) (40 microM). When the non-NMDA receptors were blocked a halothane concentration of 38.1 +/- 5.6 mg/mL was required to produce a further 50% decrease in population spike amplitude. When NMDA receptors were blocked with AP5 or only GABAA receptors were blocked the halothane concentrations needed to produce 50% block were higher than needed for the control (160.8 +/- 17.8 and 190.2 +/- 12.1 microgram/mL, respectively). These studies indicate that the NMDA receptors are more sensitive to the effects of halothane than the non-NMDA receptors.

Some effects of d-tubocurarine alone and combined with halothane or isoflurane on neuromuscular transmission.

The mechanisms contributing to the neuromuscular block produced by nondepolarizing muscle relaxants and inhaled anesthetics include: 1) receptor blockade, 2) open or closed ion channel block, 3) decreased transmitter release, and 4) receptor desensitization. In this study we investigated the contributions of receptor and ion channel block. We used the two microelectrode voltage clamp to evaluate miniature end-plate currents (MEPCs) for amplitude and time constant of decay (tau) before and after the application of 1) d-Tubocurarine (DTC) (10(-7)-10(-6) M) alone, and then 2) the same concentration of DTC plus 0.5% or 1.0% halothane or isoflurane delivered by passing compressed air through a flow and temperature compensated vaporizer. The electrodes were maintained in the same cell for the entire experiment. DTC alone decreased MEPC amplitude to 91.3% +/- 4.5% and 65.1% +/- 5.6% of control at 10(-7) and 10(-6) M, respectively. MEPC amplitude with 10(-6) M DTC decreased further to 52.4% +/- 7.6% and 37.4% +/- 7.0% of control after the addition of 0.5% and 1.0% halothane, respectively. After the application of DTC 10(-7) M tau was 94.7% +/- 3.1% of control and decreased to 73.7% +/- 7.1% of control with 10(-6) M DTC. After the application of DTC 10(-6) M the addition of 0.5% and 1% halothane decreased tau to 52.4% +/- 7.6% and 30.0% +/- 5.9% of control. Isoflurane produced similar changes. This study provides evidence that at least some of the augmentation of nondepolarizing relaxants by inhaled anesthetics can be explained by the additive effect of nondepolarizing muscle relaxants and inhaled anesthetics on MEPC amplitude and tau.

Age-induced alteration of neuromuscular transmission: effect of halothane.

Age-induced alteration in neuromuscular transmission and the effect of halothane were examined in 3- and 30-month-old rats with the voltage clamp technique. Significant pre- and post-junctional changes of synaptic transmission occur with advancing age as the frequency of spontaneous release, quantal content and mobilization rate increase and decay time (tau) of miniature end plate current (MEPC) and end-plate current (EPC) is prolonged and altered (bi-exponential). Effects of halothane (0.3-0.88 mM) appeared to be pre-junctional, as the anesthetic decreased the frequency of spontaneous release, end plate current amplitude, quantal content and mobilization rate, had little or no effect on decay time of miniature end plate current and end plate current, and produced no run-down of ionophoretically evoked trains of end plate current. Some of these effects of halothane are more prominent in 30-month-old rats.

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

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

Effect of (+/-)-DOI on neuromuscular transmission: a microelectrode study.

DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) significantly depressed end plate current (EPC) amplitude. It decreased quantum content, increased the extent of neurally evoked EPC rundown during the train, produced a nonlinear current-voltage relationship, shortened time constant of decay, and depressed iontophoretically evoked EPC. The depressant response of DOI on EPC amplitude was antagonized by 5-HT1-like receptor antagonists, but was resistant to 5-HT2 and 5-HT3 receptor antagonists. This suggests that inhibitory 5-HT receptors roughly correspond to 5-HT1-like receptors.

Anesthesia for craniotomy: a double-blind comparison of alfentanil, fentanyl, and sufentanil.

Using a prospective, randomized, and double-blind study design, alfentanil (n = 15), fentanyl (n = 14), or sufentanil (n = 16), in combination with N2O, were administered to patients undergoing craniotomy for supratentorial tumor resection. Physicians were given two syringes, one of which was labeled as "load" for the initial loading dose and the other as "maintenance" for continuous infusion. The concentration of drug in each syringe was adjusted to permit administration on a milliliter per kilogram basis. The target loading doses for alfentanil, fentanyl, and sufentanil were 75, 10, and 1 microgram/kg, respectively, and initial infusion rates were 33.5, 2.0, and 0.3 microgram.kg-1.h-1, respectively. Additional supplementary boluses and changes in maintenance infusion rate were made according to predetermined guidelines. Isoflurane, in increasing 0.2% inspired increments, was used only when the maximum allowed opioid dose had been given (i.e., supplementary bolus doses equal to 75% of the calculated loading dose or supplementary bolus doses equal to 50% of the calculated loading dose combined with a 50% increase in the maintenance infusion rate). Opioid infusions were stopped at the time of bone flap replacement. Antihypertensive medications and naloxone were subsequently given at the discretion of the anesthesiologist. Group demographics were not different. Total volumes of drug were similar among groups indicating equipotent preparations. Administration of isoflurane, antihypertensive medications, and naloxone were not different among groups. Although decreases in blood pressure seen with induction were similar among groups, alfentanil-treated patients received ephedrine more frequently before intubation. Thirty minutes after entry into the postanesthesia recovery area, respiratory rate and pH were lowest in sufentanil-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism for antagonism of paraoxon by hemicholinium-3 analogues.

In a newly synthesized series of DMAE analogues (bis-diethyl analogue of hemicholinium-3), selected chemicals (TL-402 = NAM-242 greater than JGC-VII-110) showed significant protection of mouse lethality after acute toxic doses of paraoxon (in vivo). DMAE and NAM-250 (like hemicholinium-3) showed minimal or no antagonism against paraoxon-induced toxicity in mice. Studies with DMAE analogues demonstrate weak anticholinesterase activity. The pattern for the neuromuscular inhibition of TL-402, NAM-242 and JGC-VII-110 is different from that of hemicholinium-3. LD50 studies identified compounds with less inherent toxicity (TL-402, NAM-242 and JGC-VII-110) and showed significant antagonism in contrast to DMAE and NAM-250. These chemicals (DMAE and NAM-250) are as toxic as the parent compound hemicholinium-3. All compounds in this series showed potent antinicotinic activity in different nicotinic-receptor preparations. The antinicotinic activity correlates with their action on the acetylcholine receptor-ion channel complex at frog neuromuscular junctions (in vitro). Electrophysiological studies demonstrate that the antinicotinic agents significantly depressed both the end plate current (EPC) amplitude and the time constant of decay (tau EPC) at the end plate of frog. In presence of paraoxon, voltage- and concentration-dependent shortening of tau EPC is observed which is more prominent than the decrease of the amplitude of EPC. The antinicotinic agents which showed significant antagonism of paraoxon both in vivo and in vitro (TL-402, NAM-242 and JGC-VII-110) also produced profound tetanic rundown after neurally or ionophoretically evoked EPC. These effects are voltage-dependent. The marked shortening of tau EPC, linear relationship between 1/tau vs DMAE analogue concentrations and potential-dependent tetanic rundown suggest that these analogues produce antagonism of paraoxon primarily by reducing end plate permeability by blocking nicotinic ACh-R associated ion channels in their open form. The antinicotinic activity of these agents is related to acetal or corresponding ether substitution.

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B109OU) during nitrous oxide-narcotic, nitrous oxide-halothane and nitrous oxide-isoflurane anesthesia in surgical patients.

One hundred seventeen adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-narcotic (BAL, n = 45) nitrous oxide-halothane (HAL, n = 27) and nitrous oxide-isoflurane (ISF, n = 45) anesthesia. Anesthesia was maintained with nitrous oxide (60%-70%) and oxygen (30%-40%) with end-tidal concentrations of halothane or isoflurane to yield a total MAC of approximately 1.25, or with supplemental fentanyl and thiopental as clinically indicated. Twitch response of the adductor pollicis muscle was elicited by supramaximal square wave pulses of 0.2 msec duration at a frequency of 0.15 Hz (Grass S44 stimulator) to the ulnar nerve and quantitated by a Grass FT10 transducer. Nine patients in each of the HAL and ISF groups received one of four doses of mivacurium (0.03, 0.05, 0.10 or 0.15 mg/kg). Ninety patients in the balanced anesthesia group received one of seven doses of mivacurium (0.03, 0.04, 0.05, 0.08, 0.15, 0.20, 0.25 mg/kg). The ED50, ED75 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose versus probit of maximum percentage depression of twitch height. The ED50, ED75 and ED95 for halothane and isoflurane are 0.040, 0.053 and 0.081 and 0.037, 0.043 and 0.053, respectively. The ED50, ED75, and ED95 for the balanced group are 0.039, 0.050, and 0.073 mg/kg respectively. There was no significant difference between the slopes of the HAL and BAL inhalation anesthetic dose-response curves. The slope of the ISF group was significantly than the slope of the BAL group. Intercepts of the HAL and BAL curves were not different. The isoflurane curve's intercept was significantly less than the other groups' intercepts, lying above the halothane curve, but below the BAL curve. For the 0.05 mg/kg dose, maximum block was greater in the ISF group (89.1 +/- 2.7%, n = 9) than in the HAL (70.3 +/- 7.6%, n = 9) or BAL (67.7 +/- 6.4%, n = 9) groups. At higher doses of mivacurium, isoflurane produces a greater potentiation of neuromuscular block than halothane or balanced anesthesia. There were no significant cardiovascular changes seen in any group following mivacurium doses up to 0.15 mg/kg (approximately 2xED95).

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B1090U) during nitrous oxide-fentanyl-thiopentone and nitrous oxide-halothane anaesthesia.

Seventy-two adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-fentanyl-thiopentone (BAL group) or nitrous oxide-halothane (HAL group) anaesthesia. Eighteen patients in the BAL group received an initial bolus of mivacurium, either the ED25 (n = 9) or the ED50 (n = 9) (0.03 and 0.05 mg kg-1). These doses were based on the assumption that the slope of the dose-response curve during nitrous oxide-opioid anaesthesia would be approximately the same as the slope of the neuromuscular response from the first human studies with mivacurium. Twenty-seven additional patients were allocated to subgroups of nine patients to receive mivacurium 0.04, 0.08 or 0.15 mg kg-1. Twenty-seven patients in the HAL group were allocated also to subgroups of nine patients to receive mivacurium 0.03, 0.04 or 0.15 mg kg-1. During stable anaesthesia, mean endtidal halothane concentrations were maintained at 0.49 +/- 0.01%. The estimated ED50, ED75 and ED95 for BAL and HAL groups were 0.039, 0.05 and 0.073 mg kg-1 and 0.040, 0.053 and 0.081 mg kg-1, respectively. Halothane did not potentiate maximum block or time to maximum block. Halothane did affect spontaneous recovery. With the 0.15-mg kg-1 dose, time to 95% recovery was prolonged significantly in the HAL group (30.0 (SEM 1.4) min) compared with the BAL group (24.1 (1.5) min). Recovery index from 25% to 75% recovery was also prolonged significantly in the HAL group (7.0 (0.4) min) compared with the BAL group (5.4 (0.4) min). There were no significant haemodynamic changes in groups given mivacurium doses up to and including 2 x ED95 by bolus i.v. administration.

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

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.

Halothane and isoflurane alter acetylcholine activated ion channel kinetics.

The effects of halothane and isoflurane on the acetylcholine activated ion channel were studied in the frog sartorius muscle using the two electrode voltage clamp technique. The miniature end-plate currents (MEPCs) were recorded and evaluated for amplitude, duration of growth phase and time constant of decay (tau). Both halothane and isoflurane decreased tau in a dose dependent manner. Depression of current amplitude was also dose dependent. The ED50 value indicates tau is more affected than the amplitude of MEPC. Biexponential decay phases were seen in a small fraction of cells exposed to a low concentration of halothane but not isoflurane. Biexponential decay, when seen, was more prominent at less negative clamped membrane potential. The normal linear relationship between membrane potential and tau was not altered by anesthetics.

Nicardipine HCl: clinical experience in patients undergoing anaesthesia for intracranial aneurysm clipping.

Previous studies have reported haemodynamic interactions between dihydropyridine calcium antagonists and general anaesthesia. During anaesthesia for intracranial aneurysm surgery, we prospectively compared haemodynamic values obtained from 13 patients being treated with nicardipine HCl (0.15 mg.kg-1.hr-1 IV) for cerebral vasospasm against values obtained from 11 untreated controls. Prior to induction of anaesthesia, nicardipine-treated patients had significantly elevated mean +/- SD cardiac index (5.67 +/- 1.30 vs 3.99 +/- 0.73 L.min-1.m-2) while MAP (86 +/- 10 vs 99 +/- 14 mmHg) and systemic vascular resistance (647 +/- 227 vs 1141 +/- 404 dynes.sec-1.cm-5) were reduced. Heart rate, CVP, and PACWP were similar between groups. Anaesthesia induction and tracheal intubation resulted in similar haemodynamic values between groups with the exception of CVP (10 +/- 5 vs 5 +/- 2 mmHg) and PACWP (15 +/- 5 vs 8 +/- 3 mmHg) which were elevated in the nicardipine group (P less than 0.01). Mannitol infusion and deliberate hypotension resulted in nearly identical haemodynamic responses in both groups. Nicardipine-treated patients required more intravenous fluids during the operative procedure (2.4 +/- 0.3 L vs 1.5 +/- 0.4 L, P less than 0.05) and were less likely to require isoflurane supplementation to morphine sulphate/nitrous oxide anaesthesia (P less than 0.01). In summary, our experience with nicardipine HCl revealed no major untoward effects with respect to maintenance of intraoperative haemodynamic stability despite continuous antivasospasm therapy with this vasodilator.

Nicardipine after spinal cord compression in the lamb.

To study the effects of the calcium channel blocker nicardipine on spinal cord blood flow and spinal evoked potentials, the following study was undertaken. After cord compression, which was productive of paraparesis, nicardipine was administered intravenously in 10 anesthetized lambs. Ten control animals were subjected to compression but received saline instead. Nicardipine produced a significant decrease in mean arterial pressure when compared to the control group. Thirty minutes after compression, spinal cord blood flow also was lower in the nicardipine group compared with controls. Spinal evoked potentials did not recover after compression in either group.

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia.

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the response of hand and facial muscles to non-depolarising relaxants.

This study compares the response of the muscles of the hand to those of the face during non-depolarising neuromuscular blockade. It was found that observation of the facial muscles was misleading both in terms of degree of neuromuscular blockade and adequacy of reversal.