Problem with the Vapor vaporizer.
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Biomedical subjects
Publications and source records attributed to J J Driessen.
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A case of botulism type B acquired in The Netherlands is presented. The diagnosis was made on clinical grounds and positive mouse bio-assay. The patient was a man aged 37 years. Additional evidence was obtained by electromyography, single fibre electromyography and autonomic function tests. Antitoxin was administered without side effects. The clinical outcome was good.
The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated. A large variation was observed in the plasma concentration of midazolam and between the plasma concentration of midazolam and its metabolite 1-hydroxymethylmidazolam glucuronide. The plasma albumin concentration governs the volume of distribution of midazolam. Decreased plasma albumin concentration (25 gm/L) results in an increased volume of distribution and a decreased elimination rate of midazolam. The observed plasma concentration ratio between the parent drug and its metabolite 1-hydroxymethylmidazolam glucuronide is governed by the variables of protein binding, the metabolic rate of midazolam, and the renal clearance of the glucuronide metabolite itself (which can be considered as a measure of the kidney function of the patient).
The long-term analgesic effects and the complications of epidural narcotic analgesia (ENA) were investigated in 40 cancer patients in whom systemic narcotic therapy failed to relieve pain or caused unacceptable side effects. In 32 patients, an externally fixated polyamide epidural catheter was used ("external group"), and in 8 patients, a polyurethane epidural catheter was tunneled and connected to a subcutaneous access port ("internal group"). The average duration of catheter treatment was 80.9 days (range 9-533 days). Twenty-five patients were treated as outpatients, and 15 remained hospitalized. Initially, all patients had significant or complete pain relief from 10 mg morphine/day, but the daily epidural morphine requirement showed a threefold increase during the first 3 weeks. During ENA, other methods of pain relief (radiotherapy, chemotherapy, surgery, epidural administration of local anesthetics, and nerve blocks) were necessary in 14 patients. Pharmacological side effects were of minor importance, with transient pruritus being the main subjective complaint. In the "external" group, 31 catheter replacements were necessary, mostly due to backflow of injected morphine outside the catheter. In two patients of the internal group, neurological complications occurred, but these disappeared spontaneously after removal of the system. They were presumably due to epidural fibrosis with compression of the spinal cord. Further technical improvements are necessary for the easier use and higher safety of the catheter technique.
The clinical effects and pharmacokinetics of 24 h infusion of midazolam (MDZ) during major maxillofacial surgery and postoperative observation in an Intensive Care Unit (ICU) were studied in 20 patients. During anaesthesia, infusion of MDZ at 5 mg/h combined with 67% nitrous oxide, 1.8 (s.d. = 0.8) mg of fentanyl, and 26.5 (s.d. = 11.4) mg of vecuronium, adequately suppressed clinical responses to surgical nociceptive stimuli. Postoperatively, infusion of MDZ was continued in the ICU at 5 mg/h until 9 a.m. of the first postoperative day for sedation of the intubated but spontaneously breathing patients. The depth of sedation in the ICU was scored from 1-5 (1 = "awake and tense", 5 = "unable to communicate"). During infusion the sedation score decreased from 3.8 after ICU arrival to 2.2 at 8 a.m. of the first postoperative day. Neither ventilatory nor circulatory depression were observed. After cessation of MDZ, recovery from sedation was fast. The degree of amnesia was low. During constant rate infusion no increase in plasma concentration of either MDZ or metabolites occurred. T1/2 beta of MDZ after cessation was 125 min (range 90-320) and its total body clearance was 10.5 ml/kg/min (s.d. = 3.1). The volume of distribution, clearance and T1/2 beta were significantly longer in women than in men. It was concluded that 24 h of MDZ infusion at 5 mg/h caused satisfactory ICU sedation with fast recovery, but that individual tailoring of the infusion rate may still improve the quality of sedation.
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We report a case of bilateral injury to the ulnar nerve above the level of the elbow due to a particular retractor used for high abdominal surgery. Possible mechanisms of pathogenesis and predestinating conditions are discussed.
A case is described of thoracic spinal cord compression that occurred during continuous epidural administration of morphine. Sensory loss and motor weakness in the legs disappeared after catheter removal and antibiotic treatment.
Seven intensive care patients were sedated with prolonged infusion of midazolam. One patient received a continuous infusion of midazolam for the treatment of status epilepticus. A bolus injection of 5 mg was administered, followed by infusion of 4-14 mg/hour depending on the required level of sedation. The length of infusion varied between 80 and 360 hours. The plasma concentrations of the midazolam during infusion were between 500-1000 ng/ml. All the patients were adequately sedated. The plasma elimination half-life of midazolam and its main metabolite, 1-OH-midazolam glucuronide, after stopping the infusion varied from 4-12 hours.
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.
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.
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Dantrolene plasma concentrations and renal clearance calculations in a patient undergoing major surgery are reported. The family history was positive for malignant hyperthermia. Following oral pretreatment the plasma concentrations in this patient were not noticeably different from values obtained in a study in awake volunteers and which were thought to be effective. This is the first report of dantrolene measurements made during anaesthesia and in the post-operative period.
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.
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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.
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.
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.