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J M Malinovsky

Publications and source records attributed to J M Malinovsky.

35 records · Page 2Linked to original sources
PubMed1996

Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-O2-opioid anesthesia.

After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 x ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.

Adolescent↗
PubMed1995

Motor and blood pressure effects of epidural sustained-release bupivacaine from polymer microspheres: a dose-response study in rabbits.

The incorporation of local anesthetics into injectable polymer microspheres can be useful in providing prolonged regional effects. This randomized study was designed to compare the effects of bupivacaine and bupivacaine-loaded microspheres on the time course of motor block in rabbits injected epidurally. Bupivacaine-loaded microspheres and drug-free microspheres 1-10 microns in size were devised from poly-d,l-lactic acid by using a solvent evaporation/extraction method. The effects of bupivacaine and of similar amounts of bupivacaine-loaded microspheres were studied in 26 rabbits as follows: 0.9% sodium chloride, followed by drug-free microspheres, then 1.25 mg of bupivacaine and 1.25 mg of bupivacaine-loaded microspheres (Group I; n = 8); 2.5 mg of bupivacaine, then 2.5 mg of bupivacaine-loaded microspheres (Group II; n = 8); and 5 mg of bupivacaine and 5 mg of bupivacaine-loaded microspheres (Group III; n = 10). Motor block was evaluated blindly by observation of walking disturbances, using a scale from 0 (free movements) to 3 (total limb paralysis). A period of 3 days elapsed between each injection. No limitation on movements was observed after 0.9% sodium chloride and drug-free microsphere injection. With 5 mg, both bupivacaine solutions provided complete motor block which was significantly more prolonged (+244% +/- 129%, mean +/- SD) with bupivacaine-loaded microspheres than bupivacaine. With 2.5 and 1.25 mg, block intensity was less marked, and block duration was shorter after administration of bupivacaine-loaded microspheres than after bupivacaine. We concluded that blocks resulting from bupivacaine-loaded microspheres are highly influenced by the amount of drug initially released by the polymer.

Animals↗
PubMed1995

Premedication with midazolam in children. Effect of intranasal, rectal and oral routes on plasma midazolam concentrations.

We report a study performed to compare the time and plasma drug concentrations necessary to achieve a similar state of sedation after midazolam premedication given by various routes in children of 2-5 years old. Children were randomly allocated to one of three groups to receive midazolam 0.2 mg.kg-1 given intranasally, 0.5 mg.kg-1 given orally or 0.3 mg.kg-1 given rectally. Sedation was measured regularly until venepuncture was possible in a cooperative child. At this time, a first blood sample was taken to measure plasma concentration, followed by another 10 min later. Anaesthesia consisted of intravenous propofol supplemented with regional analgesia. At recovery from anaesthesia, a third blood sample was taken. Adequate sedation occurred sooner (7.7, SD 2.4 min) with intranasal than oral (12.5, SD 4.9 min) or rectal (16.3, SD 4.2 min) midazolam. The initial blood levels were lower when the drug was given by the alimentary routes despite higher doses (146, SD 51 ng.ml-1 in 11.5, SD 3.9 min; 104, SD 34 ng.ml-1 in 21 +/- 6 min; and 93, SD 63 ng.ml-1 in 23.1, SD 3.5 min for the intra nasal, rectal and oral routes respectively). Duration of surgical procedures, and of propofol infusion, and recovery from anaesthesia was similar for the three groups. The only problem arose in a 30-month-old boy in the intranasal group who developed respiratory depression with a plasma midazolam concentration of 169 ng.ml-1. Intranasal midazolam is an excellent alternative for rapid premedication provided that respiratory monitoring is used.

Administration, Intranasal↗
PubMed1994

Acute effects of urapidil on left ventricular function in hypertensive patients: comparison with clonidine using radionuclide angiography.

We have studied the effects of urapidil 0.4 mg kg-1 i.v. and clonidine 2.5 micrograms kg-1 i.v. on left ventricular volume and function in 20 patients with chronic coronary artery disease and essential hypertension. Patients were studied using 99mtechnetium radionuclide angiography with first-pass and ECG-gated equilibrium blood-pool techniques and non-invasive sphygmomanometry. Administration of both urapidil and clonidine caused a similar decrease in mean arterial pressure (20%), associated with an equivalent reduction in systemic vascular resistance. Despite the decrease in mean arterial pressure, heart rate did not change after administration of clonidine, but there was an early and transient increase of 13% after urapidil. There were no changes in cardiac index, but in contrast with clonidine, urapidil caused a decrease in stroke index. In both groups, global left ventricular ejection fraction did not change. Urapidil produced a mean decrease in end-diastolic volume of 8% and a mean decrease in end-systolic volume of 13%, in contrast with clonidine which caused little change. Reduced arterial pressure, systemic vascular resistance and preload after urapidil 0.4 mg kg-1 i.v., associated with lack of prolonged tachycardia and preserved global left ventricular performance, may have obvious clinical implications in anaesthesia.

Adrenergic alpha-Antagonists↗
PubMed1994

Effects of oral ranitidine, famotidine and omeprazole on gastric volume and pH at induction and recovery from general anaesthesia.

We have studied, in 150 patients undergoing elective general surgery, the effect on gastric content of omeprazole 40 mg, ranitidine 300 mg and famotidine 40 mg, given orally the night and the morning before surgery. Volume and pH of gastric content were measured at induction and recovery from anaesthesia. Gastric volumes did not differ between groups. The median gastric pH was lower with omeprazole compared with ranitidine and famotidine at intubation (5.11, 7.05 and 6.99, respectively) (P < 0.001) and extubation (6.41, 6.98 and 6.96) (P < 0.001). The proportion of patients with gastric pH < 2.5 at induction was 40% for omeprazole, 12% for famotidine and 10% for ranitidine (P < 0.02); the proportion did not differ significantly at extubation.

Administration, Oral↗
PubMed1993

[Is urapidil a venodilator?].

This study aimed to assess and compare the effects of urapidil and clonidine on right ventricular volumes and function in 20 physical status ASA III patients, with a borderline untreated essential hypertension and with or without chronic coronary artery disease. The patients were randomly assigned to two equal groups to receive either urapidil (0.4 mg.kg-1) or clonidine (2.5 micrograms.kg-1). Neither patient had congestive heart failure, valvular heart disease, previous myocardial infarction, nor was any being treated with beta-blocking agents or with amiodarone. Usual anti-anginal medication (nifedipine and isosorbide) was maintained up to the time of the procedure. Monitoring was obtained from ECG, Swan-Ganz catheter fitted out with a fast response-thermistor, and radial artery cannula. Blood samples were withdrawn for plasma atrial natriuretic factor determination. Thirty minutes after catheter insertion, baseline data were collected in supine and 45 degrees head-up tilt positions. Following urapidil or clonidine i.v. injection, three series of measurements (3, 8 and 13 min) were made in supine and tilt positions according to a randomized sequence. The two groups were similar with regard to age, weight, height, coronary artery disease and treatment. Urapidil and clonidine elicited a similar decrease in mean arterial pressure of 14% in supine position and 20% in head-up tilt position, combined with an exclusive decrease in systolic index i.e. not associated with a change in peripheral vascular resistances. Despite the decrease in arterial pressure, heart rate remained unchanged. Right ventricular ejection fraction was maintained after both urapidil and clonidine, however end-diastolic and end-systolic volumes decreased, with no modification by tilting.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1993

Plasma concentrations of midazolam after i.v., nasal or rectal administration in children.

Midazolam is used frequently for premedication in children, preferably by non-parenteral administration. We have compared plasma concentrations of midazolam after nasal, rectal and i.v. administration in 45 children (aged 2-9 yr; weight 10-30 kg) undergoing minor urological surgery. General anaesthesia consisted of spontaneous respiration of halothane and nitrous oxide in oxygen via a face mask. After administration of atropine and fentanyl i.v., children were allocated randomly to receive midazolam 0.2 mg kg-1 by the nasal, rectal or i.v. route. In the nasal group, children received 50% of the dose of midazolam in each nostril. In the rectal group, midazolam was given rectally via a cannula. Venous blood samples were obtained before and up to 360 min after administration of the drug. Plasma concentrations of midazolam were measured by gas chromatography and electron capture detection. After nasal and rectal administration, midazolam Cmax was 182 (SD 57) ng ml-1 within 12.6 (5.9) min, and 48 (16) ng ml-1 within 12.1 (6.4) min, respectively. Rectal administration resulted in smaller plasma concentrations. In the nasal group, a plasma concentration of midazolam 100 ng ml-1 occurred at about 6 min. After 45 min, the concentration curves after i.v. and nasal midazolam were similar.

Administration, Intranasal↗
PubMed1993

Is ketamine or its preservative responsible for neurotoxicity in the rabbit?

BACKGROUND: Although ketamine has been administered spinally in humans, previous neurotoxicity studies have shown that it can induce spinal cord lesions in various animal models. The aim of this work was to evaluate by histologic and blood-brain barrier studies whether different components of the commercial ketamine solution might be responsible for the microscopic lesions observed. METHODS: Forty white New Zealand rabbits were randomly assigned to four groups of 10. One-percent preservative-free ketamine (0.3 ml), 1% d-ketamine, 0.05% chlorobutanol, and 1% lidocaine were intrathecally injected through the atlantooccipital membrane. Laminectomy was performed on day 8, and the dura was preserved using paraformaldehyde-glutaraldehyde fixative. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of injected agents used. Specimens were then graded as normal or abnormal as compared with a control group receiving lidocaine. RESULTS: Isomers of ketamine did not induce spinal cord lesions in either study, but chlorobutanol (the preservative used in the ketamine solution) induced significant severe spinal cord lesions in both studies. CONCLUSIONS: The appearance of spinal cord lesions after intrathecal chlorobutanol strongly suggests that this preservative is responsible for apparent toxicity of ketamine and therefore should not be used in any solution intrathecally injected into humans.

Animals↗
PubMed1991

[Comparative effects of diazepam, ranitidine , sodium citrate and enprostil on pH and gastric volume in preanesthetic medication].

A study was designed to assess the efficacy of oral premedication with diazepam or enprostil in preventing the gastric aspiration syndrome in fasted patients scheduled for elective surgery, and to compare the results with those obtained with ranitidine and sodium citrate. The study included 120 consecutive patients undergoing urological or plastic surgery, randomly assigned to four groups of 30. Two hours before anaesthesia, the patients from three groups were given, with 30 ml of water, either 10 mg diazepam, or 150 mg ranitidine, or 35 micrograms enprostil. Those in the fourth group were given 30 ml of 0.5 M sodium citrate, ten minutes before induction. Anaesthesia consisted in the administration of thiopentone, fentanyl, vecuronium and nitrous oxide in oxygen. After endotracheal intubation, a gastric tube was inserted. The stomach fluid content was completely aspirated, and then again 60 and 120 min after induction, as well as at the end of surgery. Age, weight and duration of surgery were comparable in the four groups. Mean pH in the diazepam group was much lower than that in the other groups, both just after induction (2.3 +/- 1.54; p less than 0.001 vs. ranitidine and sodium citrate; p less than 0.01 vs. enprostil) and at the end of surgery (3.2 +/- 2.03; p less than 0.01 vs. ranitidine and sodium citrate; p less than 0.05 vs. enprostil). There was more than 0.4 ml.kg-1 gastric juice in the sodium citrate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antacids↗
PubMed1991

Ketamine and midazolam neurotoxicity in the rabbit.

Ketamine and midazolam can produce analgesia following intrathecal administration in rabbits. However, neurotoxicity studies are required before these agents can be considered safe for clinical use. The aim of this study was to evaluate by histologic and blood-brain barrier (BBB) studies whether ketamine or midazolam could be used as an alternative to local anesthetics or opioids to produce spinal analgesia. Forty white New Zealand rabbits were randomly assigned to four groups of 10. In the conscious animal, 0.3 ml 0.9% saline solution, 1% lidocaine, 1% ketamine, or 0.1% midazolam was intrathecally injected intracisternally using a modification of the technique of Yaksh et al. Light and fluorescence microscopy were performed on transverse spinal cord sections by a neuropathologist unaware of the administered agents. All spinal cord section slides were scored within four zones: upper cervical, lower cervical, median thoracic, and lumbar segments. Spinal cord homogeneous lesions with higher scores than those of lidocaine-treated animals were considered abnormal. The BBB study showed evidence of neurotoxicity for ketamine, whereas light microscopy indicated no significant differences in comparison with saline and lidocaine. Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies. In view of these results, the intrathecal use of midazolam should be avoided in humans. Lesions observed following ketamine suggest the need for further experimental studies of the solvent and different ketamine enantiomers to establish definitively the safety of intrathecal free ketamine in humans.

Animals↗
PubMedDate not supplied

A chronic model for experimental investigation of epidural anesthesia in the rabbit.

BACKGROUND AND OBJECTIVES: A rabbit chronic model has been developed for investigation of epidural anesthesia without surgery. METHODS: A catheter was implanted via a nontraumatic route in the lumbar epidural space between the apex coccis sacri and the first vertebra coccygea after a 1-cm incision was made in the skin at the root of the tail. The ligamentum was punctured to allow the catheter to slide gently 10 cm into the epidural space and avoid subperiosteal soft tissue dissection. The motor block effects of epidural lidocaine and bupivacaine were studied 1 week after implantation. Three injections of lidocaine 1% (group I) or 2% (group II) or bupivacaine 0.25% (group III) or 0.5% (group IV) were given at 48-hour intervals to four rabbits in each group. Increasing concentrations (0.5%, 1.0%, and 2.0%) of lidocaine and bupivacaine (0.125, 0.25, and 0.5%) were injected into eight rabbits in each of groups V and VI. The spinal cord and meninges were examined histopathologically in eight other chronically implanted rabbits that received no drugs. RESULTS: Catheters were kept in place during 2 months in 40 rabbits without neurologic disturbance, discomfort, infection or weight loss. Complete motor block was observed during a mean 27, 43, and 51 minutes with increasing doses of lidocaine. Administration of bupivacaine 0.125% led to incomplete motor deficit in three rabbits, whereas all other rabbits exhibited complete motor block, lasting a mean of 26, 53, and 93 minutes for increasing doses. Linear relationships were found between the concentration of each drug and the duration of motor block (r = .902, P < .001 for lidocaine; and r = .857, P < .001 for bupivacaine). Repeated injections of local anesthetics produced consistent durations of motor block (Bland and Altman test). No significant histologic changes were observed. CONCLUSION: This rabbit model appears to be a suitable tool for evaluating motor block of epidural agents under standardized experimental conditions.

Anesthesia, Epidural↗
PubMedDate not supplied

Spinal clonidine fails to provide surgical anesthesia for transurethral resection of prostate. A dose-finding pilot study.

BACKGROUND AND OBJECTIVES: This study was designed to determine whether subarachnoid clonidine administration alone results in surgical anesthesia for transurethral resection of the prostate. METHODS: Blood pressure, heart rate, sedation, and sensory and motor blocks were assessed in 12 patients before and after lumbar subarachnoid injection of increasing doses of clonidine (three patients each received 75, 150, 300, and 450 micrograms doses). General anesthesia was induced at the request of the patient or surgeon, if conditions were unsatisfactory. RESULTS: Clonidine resulted in marked sedation within a mean of 19 minutes of spinal injection, and no motor block was observed. There was a 25% (range, 0-45%) reduction in mean arterial blood pressure. Although endoscopy was tolerated in all cases, general anesthesia was required when resection began, except in two patients who received 300 and 450 micrograms of clonidine, respectively. Postoperative analgesic requirements showed wide interindividual variability (mean, 6 hours; range 2-12 hours). CONCLUSIONS: Subarachnoid clonidine cannot be reliably used as the sole agent for spinal anesthesia, since general anesthesia is often required or deep sedation occurs. Increasing doses of clonidine do not prolong postoperative analgesia. Thus, clonidine could be used as a spinal analgesic but not as a spinal anesthetic.

Adrenergic alpha-Agonists↗