The comparative study of LUMIWARD immunoassay system and CAP RAST system for determination of specific IgE antibody against mite in infantile atopic dermatitis

The neuromuscular blocking effects and the reversibility of cisatracurium 0.1 or 0.15 mg.kg-1 were compared with those of atracurium 0.5 mg.kg-1 during anaesthesia with propofol, nitrous oxide and isoflurane. Neuromuscular block was monitored using train-of-four stimulation while recording the mechanomyographic response of the adductor pollicis muscle. The block was either allowed to recover spontaneously or was antagonised with neostigmine 50 micrograms.kg-1 at 10% or 25% recovery of the first twitch of the train-of-four. The median times to maximum block were 2.7, 2.2 and 1.5 min following cisatracurium 0.1 and 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1, respectively. After cisatracurium 0.1 mg.kg-1 had been given, the median time to recovery of the train-of-four ratio to 0.8 ('adequate recovery') was 74 min during spontaneous recovery, 48 min after reversal with neostigmine when the first twitch of the train-of-four had returned to 10% of control and 50 min after reversal when the first twitch of the train-of-four had returned to 25% of control. These times for cisatracurium 0.15 mg.kg-1 and atracurium 0.5 mg.kg-1 were 90, 66 and 57 min and 75, 56 and 54 min, respectively. Administration of neostigmine significantly shortened the time to adequate recovery for both drugs but there were no significant differences in the case of either neuromuscular blocking drug between the groups of patients given neostigmine at 10 or 25% recovery of the first twitch of the train-of-four.     

Writing for a medical journal

Cisatracurium (51W89) is one of the ten stereoisomers of atracurium, accounting for about 15% of the racemate. The ED95 of cisatracurium was determined to be about 50 micrograms/kg (cation, molecular weight 929), while the ED95 of atracurium (besylate salt, molecular weight 1245) was 250 micrograms/kg. Thus, on a molar basis in adult patients, cisatracurium is about 3.5 times as potent as the racemic atracurium mixture. We compared atracurium with cisatracurium in healthy adult patients and found an almost identical pharmacodynamic profile. In children, an ED95 of about 40 micrograms/kg was determined, while a 1-min-longer onset of cisatracurium was found in geriatric than in young adult patients. The presence of chronic renal failure did not prolong the duration of action of cisatracurium. The recovery of neuromuscular transmission from a cisatracurium infusion of up to 145 h was investigated in intensive care unit patients. Their time from the end of infusion to a train-of-four ratio > 0.7 (68 +/- 18 min) was on average only some 70% longer than after an infusion of cisatracurium for 2 h in normal surgical patients. In another study, no signs of histamine release nor any clinically relevant cardiovascular effects of cisatracurium were found in doses up to eight times ED95.     

Resistance to atracurium in rats with experimental inflammation: role of protein binding

The influence of altered protein binding on the neuromuscular effect of atracurium has been studied in rats with experimental inflammation induced by subcutaneous injection of turpentine oil. Doses of atracurium ranging from 0.45 to 1.5 mg.kg-1 were administered to control (n = 30) and to experimental inflammation induced rats (n = 30). Neuromuscular transmission was monitored by recording the twitch tension of the tibialis-anterior muscle elicited by stimulation of the sciatic nerve. Three effect parameters were recorded: (i) intensity of the effect, measured as percentage depression of baseline twitch tension, (ii) duration of drug action (min) and (iii) recovery time (min). The dose-intensity of the effect relationship was modelled using a sigmoid Emax model. The ED50 (effective dose eliciting 50% of the maximum effect) was significantly increased (P < 0.01) in the inflammation group as compared to the control group (0.94 vs. 0.68 mg.kg-1). This change was reflected in a shift of the dose-response curve to the right in the pretreated rats. For equipotent doses ED95 (defined as the effective dose eliciting 95% of maximum effect), no differences were found in recovery time and duration of action between the two groups of rats. Mucoproteins levels (index of alpha 1-acid glycoprotein (AAG) and protein binding were significantly increased in rats with experimental inflammation as compared to control rats. Based on these results, altered serum protein binding of atracurium appears to be responsible, at least in part, for the resistance to atracurium.     

Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia

PURPOSE: To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery. METHODS: Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 X ED90 rocuronium (0.6 mg.kg-1; n = 20) or atracurium (0.5 mg.kg-1; n = 21) during intravenous propofol/alfentanil anaesthesia with N2O/O2 ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers. RESULTS: Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 +/- 22.2 vs 98.6 +/- 41.4 sec; P < 0.001) and clinical duration of action (33.3 +/- 7.1 vs 44.7 +/- 7.2 min; P < 0.001), but longer spontaneous recovery index (9.6 +/- 2.41 vs 6.9 +/- 1.89 min; P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 +/- 6.31 vs 59.2 +/- 7.59 min; P = 0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck. CONCLUSION: Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.     

Esophageal cyst--a rare cause of backache

BACKGROUND: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. METHODS: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg.kg-1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg.kg-1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg.kg-1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. RESULTS: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). CONCLUSION: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.     

Delay of clinical recovery from paralysis induced by atracurium: comparison between orbicularis oculi and adductor pollicis

OBJECTIVE: To compare with train-of-four stimulation the delays of the beginning of the spontaneous recovery of the orbicularis oculi and of the adductor pollicis after profound neuromuscular blockade with atracurium. STUDY DESIGN: Prospective, comparative open study. PATIENTS AND METHODS: Twenty-eight physical class ASA 1 and 2 patients under general anaesthesia (propofol, N2O, fentanyl) and profound neuromuscular blockade with atracurium. Train-of-four stimulation, every 10 s, of the ulnar nerve at the wrist (for assessing by tactile means the response of the adductor pollicis) and of the temporal branch of the facial nerve (for assessing visually the response of the orbicularis oculi). On each site, measurement of the delay between the end of the maintenance of deep neuromuscular blockade (last dose of atracurium) and the beginning of the recovery (first response to train-of-four stimulation). RESULTS: In each case, the recovery of the orbicularis oculi began earlier than the recovery of the adductor pollicis (26 +/- 9 min vs 34 +/- 9 min, P < 0.001). The delays of recovery at each site were strongly correlated (r = 0.87; P < 0.001) but the time lag between the responses varied greatly: 1 to 21 min, mean: 8 +/- 5 min, coefficient of variation: 56.6%. CONCLUSION: The orbicularis oculi should not be monitored alone for assessment of recovery from profound neuromuscular blockade by atracurium, as it predicts poorly the time of the recovery of the adductor pollicis.     

The effects of age on onset and recovery from atracurium, rocuronium and vecuronium blockade

Elderly patients may show an age-related decline in physiologic functions, which may be responsible for the prolonged duration of some neuromuscular blocking agents. Previous studies have yielded conflicting results as to the effects of these drugs in the elderly. METHODS: After obtaining informed consent and approval of the Ethics Committee, we compared onset and recovery times of single IV doses of atracurium, rocuronium, and vecuronium given to 108 patients divided into three groups according to age (18-50, 51-64, > or = 65 years). Following oxazepam premedication and fentanyl and thiopentone induction, patients were randomly allocated to receive atracurium, rocuronium or vecuronium (0.5, 0.6, or 0.1 mg/kg, respectively) in < or = 0.8 vol.% enflurane (end-tidal)-nitrous oxide anaesthesia. Muscular relaxation was assessed by electromyographic (EMG) recording of the adductor pollicis muscle after supramaximal single-twitch stimulation of the ulnar nerve every 10 s. Onset time and recovery to 25%, 75% and 90% of twitch control values (DUR25, 75, 90) were recorded. Creatinine clearance predicted from serum creatinine (Ccr) was correlated with recovery from neuromuscular block. RESULTS: Onset time was not different among groups or relaxants. The results showed a prolonged duration of action for atracurium (DUR75, DUR90), rocuronium (DUR25, DUR75), and vecuronium (DUR25) in the elderly. A number of patients did not reach DUR75 or DUR90. There was a significant relationship between age and failure to return to control values during recovery from neuromuscular block, especially after atracurium and rocuronium. Ccr showed a negative correlation with age for all relaxants, but a negative significant correlation between Ccr and recovery was found only for rocuronium. CONCLUSIONS: This study suggests that onset time for atracurium, rocuronium and vecuronium is not age-dependent. Recovery was prolonged in the elderly for all three relaxants. This effect appears to be secondary to changes in body composition and function accompanying the aging process. Neither atracurium nor vecuronium depends significantly on the kidney for elimination, but the negative correlation between Ccr and rocuronium suggests an appreciable role for the kidney in the elimination of this relaxant. The long recovery times observed in this study could also be related to enflurane anaesthesia. We suggest that failure of EMG responses to return to baseline values during recovery from neuromuscular block may be related to age, especially for atracurium and rocuronium.     

Neuromuscular blockade with vecuronium and its reversal with edrophonium during total intravenous anesthesia, neuroleptanalgesia and sevoflurane anesthesia

The neuromuscular blocking effect of vecuronium and its reversibility ith edrophonium were studied under total intravenous anesthesia (TIVA) and compared with those under NLA or sevoflurane anesthesia (SA) in 30 surgical patients. The degree of neuromuscular blockade was evaluated by acceleration of thumb adduction in response to supramaximal stimulation of the ulnar nerve using Accelograph (Biometer). TIVA was induced with droperidol 0.25 mg.kg-1, fentanyl 2-4 micrograms.kg-1 and ketamine 2 mg.kg-1, and maintained with continuous infusion of ketamine 2 mg.kg-1.h-1 with 30-35% O2 in air. NLA was induced with droperidol 0.25 mg.kg-1 and fentanyl 5-10 micrograms.kg-1 and maintained with 66% nitrous oxide in oxygen. SA was induced with thiamylal 5 mg.kg-1 i.v. and maintained with 66% nitrous oxide in oxygen supplemented with sevoflurane (1 MAC). A single bolus intravenous injection of vecuronium 0.1 mg.kg-1 was used for paralysis and reversed with edrophonium 0.75 mg.kg-1 followed by atropine 0.015 mg.kg-1 when the TOF ratio returned to 25%. The times required from administration of vecuronium to completion of maximal block with TIVA, NLA and SA were 196.5 +/- 52.2 sec, 182.5 +/- 47.6 sec and 166.0 +/- 69.0 sec, respectively. There was no significant difference among them. The times from completion of maximal block to 25% recovery of the twitch height in TIVA and NLA were 39.5 +/- 11.0 min and 37.4 +/- 5.8 min without significant difference. Those values, however, were significantly shorter than 64.5 +/- 35.2 min of SA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potential of succinylcholine-induced neuromuscular blockade by nitrous oxide

To evaluate the potentiating effect of nitrous oxide on the succinylcholine (SCh)-induced neuromuscular blockade, 0.16, 0.20, 0.25 or 0.31 mg.kg-1 of Sch was given during thiamylal-fentanyl anesthesia with or without nitrous oxide, and the evoked electromyograph of hypothenar muscles was measured. ED50 and ED95 in the group receiving nitrous oxide were 0.187 and 0.301 mg.kg-1, and 0.218 and 0.389 mg.kg-1 in the group not receiving nitrous oxide respectively. In the presence of nitrous oxide, the dose-response curve (DRC) was shifted to the left significantly (P < 0.01). By the multiple regression analysis, the degree of the neuromuscular blockade was shown to be affected by dose and nitrous oxide. It was demonstrated that nitrous oxide decreased electromyographically measured SCh requirements by 16.1%. In addition, the dose-effect relationship for SCh-induced neuromuscular blockade varied widely, and gender did not affect the degree of block.     

Influence of graded changes in vasomotor tone on the carotid arterial mechanics in live spontaneously hypertensive rats

1. The contribution of vasomotor tone to the increased stiffness of carotid arteries in living spontaneously hypertensive rats (SHR) is largely unknown. Whether a reduced vascular tone is associated with an increase or a decrease in arterial stiffness in vivo remains to be determined. The goal of the present investigation was to show that a decrease in vascular tone is associated with a decrease in arterial stiffness, independent of the structural composition of the arterial wall. 2. New high resolution echo-tracking techniques were used to evaluate pulsatile changes of carotid blood pressure and diameter following transient and graded changes of vasomotor tone produced by the dihydropyridine derivative, isradipine. Treatment for 8 weeks was given to groups of SHR rats either with a low (0.6 kg day-1) or a high (2.6 mg kg-1 day-1) dose. Another SHR group received an acute dose of 2.6 mg kg-1 day-1. Results were compared to those of placebo-treated Wystar-Kyoto (WKY) and SHR rats. Whatever the dosage, acute or chronic calcium blockade caused a decrease in blood pressure which was maximal 1 h after administration and disappeared after the 16th h. Carotid arterial thickness and the composition of the arterial wall was determined from histomorphometry. 3. In placebo-treated SHR, the inverse relationship relating blood pressure to carotid arterial distensibility was significantly shifted toward higher values of blood pressure compared to the curve of normotensive placebo-treated WKY rats. The curve of SHR receiving chronically a non antihypertensive (0.6 mg kg-1 day-1) isradipine dose prolonged that of placebo-treated SHR toward lower values of blood pressure, so that carotid distensibility was significantly higher than in WKY for the same diameter and blood pressure level (145 mmHg). With administration of a chronic antihypertensive dose (2.6 mg kg-1 day-1) causing a significant decrease in arterial function. Acute antihypertensive calcium blockade with a single isradipine dose (2.6 mg kg-1 day-1) caused a similar shift in the pressure-distensibility curve toward the WKY curve although the histomorphometric composition of the arterial wall differed significantly from that of chronically treated animals. 4. The study provides evidence that, in living SHR submitted to calcium blockade, (i) a low dose of isradipine causing no substantial antihypertensive effect is associated with a significant elevation of carotid arterial distensibility for the same pressure and diameter as normotensive controls, and (ii) an acute or chronic dose causing a substantial antihypertensive effect is associated with a transient shift of the SHR distensibility-pressure curve toward a physiological arterial function, increasing carotid distensibility for the same pressure and diameter as WKY controls. Since such findings were observed independently of the histomorphometric composition of the arterial wall, they imply that the transient decrease in arterial stiffness produced by calcium blockade should involve specific changes in the connections between arterial smooth muscle and extracellular matrix.     

Value of the monitoring of curarisation during prolonged mivacurium induced neuromuscular block

A case of neuromuscular blockade of about 200 min of duration, in a 9-year-old boy from mivacurium 0.15 mg.kg-1 is reported. The diagnosis was delayed, after onset of the first signs of recovery, due to the lack of monitoring of neuromuscular transmission. The neuromuscular blockade was reversed with neostigmine 0.04 mg.kg-1. Complete reversal required fifty minutes. The presence of an abnormal genetic variant of pseudocholinesterases was demonstrated by the measurements of pseudocholinesterase activity and dibucaine number. The importance of monitoring of neuromuscular transmission for diagnosis and treatment of mivacurium-induced neuromuscular blockade is underlined.     

Comparison of [123I]beta-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates

The aim of our randomized controlled study was to compare the neuromuscular characteristics of mivacurium and atracurium by evaluating the intubation conditions, intubation times, onset times and the duration of action of these two muscle relaxants using two different dosing principles. Forty-eight patients were included in this study. All patients were premedicated orally with 0.2 mg/kg diazepam. Anaesthesia was induced with 2.0 mg/kg propofol and 0.02 mg/kg alfentanil and maintained with 6 mg/kg/h propofol and 60% nitrous oxide in oxygen. Neuromuscular monitoring was carried out with supramaximal TOF-stimulation (2 HZ) of the ulnar nerve every 10 seconds and recording of the mechanomyogram (MMG) (Myograph 2000, Biometer) at the adductor pollicis muscle. The patients of group 1 (n = 12) received an intubation dose of 0.15 mg/kg mivacurium (2 x ED95) and the patients of group 2 (n = 12) received a priming dose of 0.015 mg/kg mivacurium (20% of ED95) followed by an intubation dose of only 0.07 mg/kg mivacurium (ED95) two minutes later. The patients of group 3 (n = 12) were intubated with 0.46 mg/kg atracurium (2 x ED95) and the patients of group 4 (n = 12) received a priming dose of 0.046 mg/kg atracurium (20% of ED95) and an intubation dose of 0.23 mg/kg atracurium (ED95) four minutes later. The patients were intubated under normocapnic conditions and following stabilisation of the palmar skin temperature after a 90% neuromuscular block (T1) had occurred. The intubation conditions were measured semiquantitatively using an intubation score.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of premedication on dose requirements for propofol: comparison of clonidine and hydroxyzine

The influence of a single dose of clonidine (5 micrograms kg-1) or hydroxyzine (1 mg kg-1) on intraoperative propofol requirements was determined in 28 male patients (ASA I) undergoing elective orthopaedic surgery. Patients were randomly allocated to receive either clonidine or hydroxyzine orally 2 h before induction of anaesthesia. After a loading dose of propofol (2.5 mg kg-1), mivacurium (0.2 mg kg-1) and alfentanil (15 micrograms kg-1), anaesthesia was maintained with a standardized propofol infusion supplemented with nitrous oxide (66%) in oxygen. During surgery, additional propofol boluses (1 mg kg-1) were administered when heart rate or mean arterial pressure increased by more than 10% compared with preinduction values. The clonidine group demonstrated a 14.5% decrease in total propofol requirements (P < 0.05) and a 52.2% reduction in additional propofol boluses (P < 0.02) in comparison with the hydroxyzine group. intraoperative heart rate and mean arterial pressure were significantly lower in the clonidine group but no patients needed treatment with ephedrine for hypotension or bradycardia. Recovery of psychomotor function and discharge from the recovery room were not delayed in the clonidine group. This study indicates that 5 micrograms kg-1 clonidine given as premedication in ASA I patients reduces intraoperative propofol requirements in comparison with 1 mg kg-1 hydroxyzine without inducing adverse effects on recovery or haemodynamic stability.     

Dose-response relationship of atracurium besylate in the halothane-anaesthetised pig

The dose response relationship for the intermediate-acting non-depolarising muscle relaxant, atracurium besylate in the pig was determined using evoked electromyography. An incremental dose technique was used in seven Large White/Landrace crossbred pigs anaesthetised with nitrous oxide and halothane. ED50 and ED95 were 510 +/- 87 micrograms kg-1 and 1150 +/- 270 micrograms kg-1, respectively. Although these values may represent an overestimate, they provide a reasonable guideline for the use of atracurium by veterinary anaesthetists.     

Pharmacokinetics and dosage regimens of amikacin in intensive care unit patients

The pharmacokinetics of amikacin have been studied in 40 intensive care unit (ICU) patients using a two-compartment model and the Bayesian estimation method implemented in the USC PC-PACK program of Jelliffe et al. The volume of the central compartment was significantly higher in these patients (0.36 l.kg-1) than in the reference population (0.20 l.kg-1). A method has been designed to compute dosage regimens in order to maintain a constant steady-state average plasma concentration of 8 mg.l-1 for repeated i.v. infusions. The regimen calculated for the 'average' ICU patient varies between 11 mg.kg-1 three times per day for the patient with normal renal function and 6 mg.kg-1 every 2 days for the anuric patient. This regimen is intended to begin amikacin therapy in an ICU patient, while the population pharmacokinetic parameters would allow the individualization of the regimen by means of the Bayesian method.     

Experimental grounds for using chlorin e6 in the photodynamic therapy of malignant tumors

The toxicity, pharmacokinetics and antitumour effect of chlorin e6 after light irradiation were studied. The LD50 value of chlorin e6 in C3H mice is 189 +/- 9 mg kg-1 and in Wistar white rats is 113 +/- 18 mg kg-1 14 days after intraperitoneal injection. The concentration of chlorin e6 in blood, liver, kidney, spleen and tumors (sarcoma M-1 and sarcoma 45) of the rats was determined by a fluorescence method, 3, 6, 12, 18, 24, 48 and 72 h after administration at a dose of 10 mg kg-1. For this purpose, chlorin e6 was extracted from tissues by the detergent Triton X-100. The depth of necrosis in sarcoma 45, the regression rate of sarcoma M-1 and the animal cure rate were evaluated after chlorin e6 administration at doses of 1-10 mg kg-1 and subsequent irradiation with krypton laser light. Depending on the dose and the time interval between chlorin e6 injection and irradiation, the depth of necrosis in sarcoma 45 varied from 5.0 to 15.0 mm. The cure rate of the animals with sarcoma M-1 varied from 10% to 60%. The antitumor effect was directly proportional to the chlorin e6 dose and light energy exposure and inversely proportional to the time interval between photosensitizer injection and irradiation.     

Interactions between suxamethonium and mivacurium or atracurium

We have compared the dose-response relationships of suxamethonium, mivacurium and atracurium and examined the interactions of suxamethonium with mivacurium or atracurium in humans by isobolographic analysis. We studied 100 adult patients during fentanyl and thiopentone anaesthesia. Neuromuscular function was monitored using a Myograph 2000 (Biometer Co., Odense, Denmark). The dose-response curves were determined by probit analysis. Isobolographic and fractional analyses were used to assess quantitatively the combined effect of equipotent doses of suxamethonium, mivacurium and atracurium and to define the type of interaction between suxamethonium and mivacurium or atracurium. The ED50 values for suxamethonium, mivacurium and atracurium were 198.8 (95% confidence interval 190.7-206.9), 48.6 (45.4-51.8) and 202.1 (197.9-206.2) mg kg-1, respectively. Isobolographic and fractional analyses of the suxamethonium-mivacurium and suxamethonium-atracurium combinations demonstrated antagonistic interactions.     

Support of renal blood flow after ischaemic-reperfusion injury by endogenous formation of nitric oxide and of cyclo-oxygenase vasodilator metabolites

1. Ischaemia-reperfusion injury in the kidney is associated with a loss of autoregulation, an increase in renal vascular resistance (RVR), a decrease of renal blood flow (RBF) and ultimately acute renal failure. The aim of this study was to investigate the role of the release of endogenous nitric oxide (NO) in the recovery of RBF after ischaemic injury of the renal vascular bed. 2. Anaesthetized rats (thiopentone sodium; 120 mg kg-1, i.p.) were submitted to acute renal ischaemia followed by 2 or 6 h of reperfusion (I/R). Reperfusion was associated with a significant reduction in RBF, an increase in RVR, and an impairment of the vasodilator effect of acetylcholine (ACh). 3. NG-nitro-L-arginine methyl ester (L-NAME, 30 micrograms kg-1 min-1, i.v., n = 5) significantly prevented the recovery of RBF after I/R injury. Similarly, inhibition of prostanoid formation with indomethacin (5 mg kg-1, i.v., n = 4) significantly enhanced the rise in RVR associated with I/R injury. 4. Infusion of L-arginine (L-Arg; 1 or 3 mg kg-1 min-1, i.v., n = 5 and 4, respectively) or D-Arg (1 mg kg-1 min-1, i.v., n = 6), starting 30 min after occlusion, did not improve the recovery of RBF. Furthermore, infusion of L-Arg (20 mg kg-1 min-1 for 15 min; n = 4) had no effect on the I/R-induced impairment of the vasodilator responses to ACh. 5. To elucidate the relative importance of the constitutive and inducible NO synthase isoforms for the formation of NO after I/R, calcium-dependent (constitutive) and calcium-independent (inducible) NO synthase activities were measured in kidney homogenates obtained from ischaemic or non-ischaemic kidneys. A calcium-independent NO synthase activity was not detectable in kidney homogenates obtained from either sham-operated control rats or from animals subjected to I/R. Moreover, dexamethasone(3 mg kg-1, i.v., 60 min prior to I/R, n = 6), an inhibitor of the induction of NO synthase,had no effect on either RBF or RVR in rats subjected to I/R. In contrast to I/R, lipopolysaccaride(LPS, endotoxin; 5 mg kg-1, i.p., n = 3) caused a significant induction of a calcium-independent NO synthase activity in the kidney.6. These results confirm the importance of the release of vasodilator cyclo-oxygenase metabolites in the compromised renal circulation and indicate that the formation of NO derived from the constitutive, but not the inducible NO synthase, is also important for the maintenance of RBF after I/R injury of the renal vascular bed.     

Two circuits to convert short-term memory into long-term memory

In this prospective study we tested the hypothesis that atropine administration, which is known to increase heart rate and cardiac output in infants, will result in a faster onset of neuromuscular block with atracurium. Thirty infants scheduled for elective surgery had anaesthesia induced with nitrous oxide and halothane. Fifteen patients were given atropine and 15 patients acted as controls. All the infants were given atracurium 0.5 mg.kg-1, and neuromuscular block was recorded with the Datex 221 neuromuscular transmission monitor. Although atropine caused an increase in heart rate compared to the control group (median 164 [range 151-182] vs 120 [98-160]min-1 P < 0.0001), there was not a statistically significant difference in the onset of neuromuscular block between the two groups. We conclude that onset of neuromuscular block after atracurium is determined mainly by noncirculatory factors and less by the circulation time to the muscle. The effect of atropine on the time course of neuromuscular block might be different with faster acting neuromuscular blockers.