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Biomedical subjects

J F Crul

Publications and source records attributed to J F Crul.

At least 37 records · Page 2Linked to original sources
PubMed1987

Post-operative analgesia by high thoracic epidural versus intramuscular nicomorphine after thoracotomy. Part III. The effects of per- and post-operative analgesia on morbidity.

One hundred and twenty-nine patients were subjected to three different types of thoracic operations. The patients were randomly allocated to balanced intravenous anaesthesia including i.v. nicomorphine during surgery and epidural nicomorphine post-operatively (epidural group, n = 58) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation and with post-operative intramuscular nicomorphine (intramuscular group, n = 71). Post-operative nicomorphine was only given at the request of the patients, and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group were given nicomorphine exclusively by epidural injection. Post-operatively, both groups (i.m. and epidural) obtained effective and rapid onset of analgesia, but the pain assessments by the patient and the medical team favoured the epidural group. The requirements of nicomorphine over a period of 3 days were significantly lower in the epidural group 42 mg (s.d. = 18) versus 92 mg (s.d. = 33) in the intramuscular group. Significantly fewer pulmonary complications were observed in the epidural group: 7 atelectases compared to 27 in the intramuscular group. The epidural group showed no signs of ventilatory depression in spite of a catheter inserted at the T3-T4 level.

Analgesia↗
PubMed1987

Effects of two benzodiazepines and a benzodiazepine antagonist on neuromuscular blockade in the anaesthetized cat.

The interaction of diazepam and midazolam with non-depolarizing neuromuscular blocking drugs was studied in the sciatic nerve-tibialis anterior muscle preparation of the anaesthetized cat. Both diazepam and midazolam (0.3 mg/kg i.v.) caused a significant enhancement of a constant 50% neuromuscular block, produced by infusions of vecuronium or pancuronium. Increasing the dose of midazolam from 0.3 to 1.5 mg/kg, caused no significant further potentiation of vecuronium, but decreased the onset time of potentiation. Ro 15-1788, a selective benzodiazepine antagonist, did not antagonize the vecuronium potentiation caused by midazolam 0.3 mg/kg. However, when given before midazolam (1.5 mg/kg), Ro 15-1788 delayed the onset of potentiation. Ro 15-1788 antagonized and prevented the considerable blood pressure decrease produced by midazolam 0.3 and 1.5 mg/kg. There appears to exist a ceiling to the benzodiazepine-induced blood pressure decrease and potentiation of vecuronium in the cat.

Animals↗
PubMed1986

Benzodiazepines and neuromuscular blocking drugs in patients.

The interaction between four benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and two nondepolarizing neuromuscular blocking drugs (vecuronium and atracurium) was investigated in 113 patients during general anaesthesia. Neuromuscular function was monitored by recording the mechanical twitch tension of the adductor pollicis muscle of the thumb in response to ulnar nerve stimulation with single supramaximal stimuli of 0.2 ms at 0.1 Hz. In the first group of patients a benzodiazepine (diazepam 20 mg, lorazepam 5 mg, lormetazepam 2 mg or midazolam 15 mg), was injected i.v. 15 min before a single bolus of vecuronium 45 micrograms kg-1. In the second group of patients suxamethonium 1 mg kg-1 was given for endotracheal intubation, and 30 min later the patients received atracurium 200 micrograms kg-1. Fifteen min before injection of atracurium one of the same benzodiazepines as in the first group was injected i.v. Comparisons were made with control patients receiving thiopentone. Neither benzodiazepine caused significant potentiation of neuromuscular blocking agents in comparison with control. With midazolam, however, the duration to 25% and to 75% recovery of the twitch height after vecuronium was significantly longer than with diazepam. The time to 25% recovery of the twitch height after atracurium was significantly longer in patients receiving midazolam than in those receiving diazepam. The recovery index was not influenced by the four benzodiazepines.

Anesthesia↗
PubMed1986

Convulsive effects and pharmacokinetics of laudanosine in the rat.

Laudanosine, which is a degradation product of atracurium, is a convulsant drug in the rat. Laudanosine plasma concentrations were measured by high performance liquid chromatography after administration of both laudanosine and atracurium; protein binding and renal excretion of laudanosine were also determined. A continuous laudanosine infusion of 25 mg kg-1h-1, or less, did not cause convulsions. Eight times ED90 for twitch depression of atracurium gave rise to a laudanosine plasma concentration of less than 8 micrograms ml-1. The convulsive plasma-concentration level for laudanosine was over 17 micrograms ml-1 in the rat. The protein binding of laudanosine was 80%. The kidney excreted 15-20% laudanosine. We conclude that convulsive levels of laudanosine will be very unlikely in any species provided that normal atracurium doses are used no matter how long the procedure.

Animals↗
PubMed1985

Interaction of midazolam with two non-depolarizing neuromuscular blocking drugs in the rat in vivo sciatic nerve-tibialis anterior muscle preparation.

Studies of the possible interactions between the water-soluble benzodiazepine, midazolam, and two non-depolarizing neuromuscular blocking drugs, vecuronium and tubocurarine, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. Midazolam 0.5 and 5 mg kg-1 caused 17% and 34% depression of the twitch height, respectively, once a steady-state blockade of the twitch height had been induced by vecuronium. The potentiation of the tubocurarine steady state blockade by midazolam 5 mg kg-1 was quantitatively equal to that of vecuronium, but was slower in onset. The buffer solvent of midazolam 5 mg kg-1 did not change the steady-state blockade of vecuronium. Midazolam 5 mg kg-1 caused a shift to the left of the cumulative dose-response curves of vecuronium.

Animals↗
PubMed1985

Invasive v. non-invasive measurement of arterial pressure. Comparison of two automatic methods and simultaneously measured direct intra-arterial pressure.

Two indirect arterial pressure monitors, the Finapres and the Accutorr, were investigated and compared with the direct measurement of intra-arterial pressure. Pressures in patients in a variety of circulatory states were measured and analysed in relation to two types of random error: first, the "intra-individual standard error" (within one session of measurement) and second, the "inter-individual standard error" (between sessions). (This distinction is important, since in routine monitoring of arterial pressure one is usually dealing with the first type of error only.) This study showed that sudden changes in pressure were closely followed by the Finapres. A pressure reading of the Accutorr takes about 15-20 s, meaning that, within this period, variations will not be observed. The accuracy or reproducibility of each method, as expressed in intra-individual variance, diminished in the order Intra-Arterial-Line, Finapres, Accutorr. The inter-individual variation decreased in the order Intra-Arterial-Line, Accutorr, Finapres. Most of the inter-individual variance of the Finapres is probably real because of the more peripheral position of its cuff. A correlation between malfunctioning of the Finapres and vasoconstriction or hypothermia of the finger could not be demonstrated.

Blood Pressure↗
PubMed1985

Post-operative analgesia by epidural versus intramuscular nicomorphine after thoracotomy. Part I.

One hundred and sixty-three patients subjected to three different types of thoracic operation were allocated randomly either to balanced intravenous anaesthesia including i.v. opiates with post-operative intramuscular opiates (intramuscular group) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation as well as epidural nicomorphine post-operatively (epidural group). Post-operative nicomorphine was given only at the request of the patient and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group received nicomorphine exclusively by epidural injection. In this paper (Part I), general parameters between the epidural group and the im. group are compared. The epidural group showed acceptable cardiovascular stability during the operation. With the catheter tip at the T3-T4 level, there was apparently a preferential spread downwards of the local anaesthetics. Post-operatively both groups (i.m. and epidural) provided effective and rapid onset of analgesia. There were no major differences in post-operative pain assessment, either by the patient or by the team.

Adolescent↗
PubMed1985

Post-operative analgesia by epidural versus intramuscular nicomorphine after thoracotomy. Part II.

One hundred and sixty-three patients subjected to three different types of thoracic operation were allocated randomly either to balanced intravenous anaesthesia including i.v. opiates with post-operative intramuscular opiates (intramuscular group) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation as well as epidural nicomorphine post-operatively (epidural group). Post-operative nicomorphine in either group was given only at the request of the patient and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group were given nicomorphine exclusively by epidural injection. Patients in the epidural group required significantly less nicomorphine for effective pain relief (29 mg (sd = 10) over a period of 3 days compared to 52 mg (sd = 27) in the intramuscular group. Significantly fewer pulmonary complications in the epidural group were observed (9 atelectases in 83 patients in the epidural group compared to 24 atelectases in 80 patients in the intramuscular group). Only one patient developed pneumonia (intramuscular group). Although the epidural catheter was inserted at the T3-T4 level, no signs of ventilatory depression were found; on the contrary, respiration in the epidural group was significantly better than the intramuscular group. None of the patients, in either analgesia group, needed to be ventilated post-operatively.

Adolescent↗
PubMed1985

The in vitro effects of benzodiazepines on the rat diaphragm. Structure-activity relationships.

The effect of three different subgroups of benzodiazepines on the indirectly evoked twitch tension was investigated in the in vitro rat phrenic nerve - hemidiaphragm preparation. Two effects were observed: an initial increase in twitch tension at lower concentrations with some benzodiazepines, and a concentration-dependent depression at higher concentrations with all benzodiazepines. Significant differences for these effects were observed among the three subgroups of benzodiazepines and additionally within the subgroup of the 1,4-benzodiazepine-2-ketones. Structural requirements for both effects were different. For the increase of twitch tension a --CH3 substitution at R1 and a --F substitution at R2' were beneficial. For the twitch depression an --OH substitution at R3 and a --C1 substitution at R2' were optimal. An interaction between substituents at different substitution sites occurred. The potency of twitch depression showed a good correlation with literature reports of pKa values and a poor-to-inverse correlation with lipophilicity indices. A benzodiazepines antagonist, Ro 15-1788, caused no change in twitch tension in the concentration range of the investigated benzodiazepines nor did it prevent the twitch depression caused by benzodiazepines.

Animals↗
PubMed1985

Interaction of some benzodiazepines and their solvents with vecuronium in the in vivo rat sciatic nerve-tibialis anterior muscle preparation.

Interaction studies between different injectable benzodiazepines and vecuronium, a non-depolarizing neuromuscular blocking drug, were performed in the rat in vivo sciatic nerve-tibialis anterior muscle preparation. The investigated doses were aimed to be "sedative" in the rat. A significant antagonism of a steady state depression of the twitch height induced by vecuronium was observed during approximately 10 min after i.v. injection of those benzodiazepines containing organic solvents in their formulations (diazepam, desmethyldiazepam, oxazepam, temazepam, lorazepam and lormetazepam). This antagonism is mainly due to propylene glycol, the main organic solvent for the poorly water-soluble benzodiazepines. After the initial antagonism, a potentiation of the vecuronium-induced depression occurred with some of these benzodiazepines (diazepam, desmethyldiazepam, temazepam and lormetazepam). Two water-soluble benzodiazepines, midazolam and flurazepam, caused a significant potentiation of the vecuronium-induced block. Important side-effects (blood pressure drop, convulsions, hematuria) were observed with the amount of propylene glycol present in the investigated formulation of lormetazepam.

Animals↗
PubMed1985

Lack of effects of emulsified propofol ('Diprivan') on vecuronium pharmacodynamics--preliminary results in man.

The possible interaction between vecuronium and propofol or thiopentone has been investigated. Cumulative dose response curves for vecuronium and the pharmacodynamic variables measured were similar with both anaesthetic agents. Patients were intubated following the topical application of lignocaine to the larynx and before the administration of vecuronium. A greater degree of relaxation of the vocal cords was noted in patients anaesthetized with propofol.

Adolescent↗
PubMed1985

Pharmacodynamics of vecuronium, atracurium, tubocurarine and their combinations in the rat in vivo.

In the in vivo rat sciatic nerve tibialis muscle preparation the potency and pharmacodynamics of vecuronium, atracurium, pancuronium, tubocurarine and their combinations were studied. Considering the potency only, there was no beneficial difference between the pure compounds and their combinations. As both vecuronium and atracurium are almost free from side-effects individually, a combination of the two relaxants brings no advantage.

Animals↗
PubMed1985

Muscle relaxants for out-patient procedures.

The requirements for muscle relaxation in out-patient anesthesia are: a short total relaxation enabling the induction of an endotracheal tube followed by a period of 15-20 minutes of clinical relaxation. Reversal should be spontaneous. The new short acting muscle relaxants vecuronium and atracurium enable such a procedure, provided small doses are used (0.045 mg/kg for vecuronium or 0.2 mg/kg for atracurium. These small doses require a longer waiting time before intubation is easily performed (5 min for vecuronium and 6 min for atracurium). Spontaneous reversal of these small doses is achieved within 20-30 minutes. Potentiation of the relaxation by inhalational agents is not recommended.

Ambulatory Surgical Procedures↗
PubMed1985

Propofol ('Diprivan') emulsion for total intravenous anaesthesia.

Propofol as an hypnotic in combination with fentanyl and vecuronium was used for total intravenous anaesthesia in 30 healthy unpremedicated patients undergoing elective surgery scheduled to last no longer than 1 h. Induction with propofol 2 mg/kg and fentanyl 1.875 micrograms/kg resulted in cessation of counting after 39 s and the loss of the eyelash reflex after 57 s. Mean recovery times, measured from the end of the infusion of propofol (9 mg/kg/h) and fentanyl (7.5 micrograms/kg/h) until eyes opened on command and questions answered correctly were 10.5 and 11.5 min, respectively. Trieger test, performed 3 h postoperatively, showed no difference in comparison with the preoperative score. During longer procedures there was evidence of accumulation in that propofol utilization rate decreased as the duration of anaesthesia increased. The results obtained are similar to those described with the previous Cremophor formulation although greater variability in induction and recovery times was noted with the emulsion formulation.

Adult↗
PubMed1984

In vitro interaction of diazepam and oxazepam with pancuronium and suxamethonium.

In vitro studies using the rat phrenic nerve-hemidiaphragm preparation were performed to investigate the effects of diazepam and three of its metabolites on indirectly evoked twitch tension. Diazepam, desmethyldiazepam and temazepam alone caused an increase in twitch tension in lower concentrations, followed by complete depression in higher concentrations. Oxazepam did not cause an initial increase in twitch tension, but showed an immediate and dose-dependent depression. Cumulative concentration-response curves for pancuronium and suxamethonium in the presence of different concentrations of diazepam or oxazepam showed that small concentrations of diazepam, which did not change twitch tension alone, caused antagonism of the action of pancuronium, but not of suxamethonium. With oxazepam no such antagonism was observed. In liminal and supraliminal concentrations, both diazepam and oxazepam potentiated the action of pancuronium and suxamethonium. Possible implications for in vivo interactions are discussed.

Animals↗
PubMed1984

In vivo induced malignant hyperthermia in pigs. I. Physiological and biochemical changes and the influence of dantrolene sodium.

The effects of an induced malignant hyperthermia (MH) crisis have been studied in the intact pig. Both physiological and biochemical changes in skeletal muscle were studied. MH was induced with 3% halothane plus a bolus injection of succinylcholine. In the prechallenge period a significant difference was observed in the concentration of certain muscle metabolites, comparing the MH-susceptible (MH+) with the non-susceptible (MH-) pigs. A lower level was measured for phosphocreatine (PCr), inosine monophosphate (IMP) and an increased level of lactate and creatine (Cr) in the susceptible pigs (MH+). The challenge caused a significant reduction of the level of PCr and adenosine in MH+ pigs, compared to the prechallenge period. After administration of dantrolene sodium, a significant decrease was measured in the level of lactate, compared to the prechallenge period as well as during the challenge. In contrast, in the control pigs no significant changes were observed in muscle metabolites, either after induction of MH or after the administration of dantrolene sodium. Enzyme activity determinations of muscle adenylate kinase and adenosine monophosphate (AMP)-deaminase did not show any difference in activity either before or during the MH crisis or after treatment with dantrolene sodium. The earliest physiological change during an induced MH crisis in our study was the rapid increase of the end-tidal CO2. Within 5 min after MH induction, end-tidal CO2 was doubled. It is concluded that the monitoring of the end-tidal CO2 is essential to diagnose MH at a very early stage.

Adenosine↗
PubMed1984

Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation.

The effect of equimolar cumulative concentrations of 11 different benzodiazepines on the indirectly evoked twitch contraction was investigated in the rat in-vitro phrenic nerve-hemidiaphragm preparation. Depending on the pattern of the concentration-response curves two groups of benzodiazepines can be distinguished: (i) a first group with a biphasic action, e.g. potentiation of twitch tension in low concentrations and depression of twitch tension in high concentrations, and (ii) a second group with primary depression of twitch tension with increasing concentrations. All of the tested compounds ultimately caused a 100% depression of twitch tension at concentrations ranging from 0.175 to 0.35 mmol litre-1. Although this peripheral effect of benzodiazepines on neuromuscular function is not the main site of action of these compounds, there are enough arguments to state that it is not a simple toxic effect. There is some evidence from this study that the peripheral component of the benzodiazepine effect on muscle relaxation may involve a multi- rather than one single receptor system.

Animals↗