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Biomedical subjects

M Bahar

Publications and source records attributed to M Bahar.

At least 37 records · Page 2Linked to original sources

An investigation of the possible neurotoxic effects of intrathecal midazolam combined with fentanyl in the rat.

In previous work, midazolam was injected intrathecally and produced reversible, segmental, spinally mediated anti-nociception sufficient for abdominal surgery in a rat model. The neurotoxic effect of midazolam, alone or combined with fentanyl, injected intrathecally repeatedly on 15 occasions over a period of 1 month, was studied in the same model. We sought to establish whether this would produce neurological damage or neurotoxic injury. Histopathological examination of the excised spinal cord and paraspinal tissues was carried out. Thirty Wistar strain rats with nylon catheters chronically implanted in the lumbar subarachnoid space were divided into five groups: group 1 (n = 6) received 40 microL of midazolam 0.1%; group 2 (n = 6) received 40 microL of fentanyl 0.005%; group 3 (n = 6) received 20 microL of midazolam 0.1% plus 20 microL of fentanyl 0.005%; group 4 (n = 6) received 40 microL of lignocaine 2%; group 5 (n = 6) received 40 microL of phenol in water. All substances were injected through the implanted catheters. The neurological recovery of all the animals in the four groups that received intrathecal midazolam alone, fentanyl alone, midazolam plus fentanyl and lignocaine alone was similar and complete. There were no significant differences in the histological changes in the neural tissues of these groups, despite repeated application of the test substances. Group 5 demonstrated the typical neurolytic lesions of phenol when injected intentionally into the subarachnoid space.

Analgesics, Opioid↗

Is it possible to recover from uncal herniation? Analysis of 71 head injured cases.

BACKGROUND: Uncal herniation (UH) caused by head trauma may become a fatal process if not treated rapidly. METHODS: We analysed the factors affecting the outcome in 71 surgically treated patients who had intracranial haematoma diagnosed by computerized tomography (CT), between January 1987 and June 1994 with the symptoms of UH. Age, incident-treatment interval, Glasgow Coma Scale (GCS), type of the lesion and the presence of polytrauma were correlated with Glasgow Outcome Scales (GOS) using SPSS PC+ statistical software. RESULTS: 49.3% of our patients were referred because of a fall from a height and 46.5% because of a motor vehicle accident. 12.7% of the patients were polytraumatized. The mean GCS of the series was 5.662. The mean GCS of the patients expired and who were in good recovery state were 4.8 and 6.9 respectively. Age, presence of polytrauma, type of the lesion and time interval between the incident and the treatment was found to be statistically insignificant when correlated with GOS. The correlation value between the GCS values and GOS was found to be highly significant (p < 0.00001). CONCLUSIONS: The findings showed that the degree of the herniation is the most important factor that affects the prognosis of the patients with UH. The reversibility of UH becomes more difficult if there are complications added during the grades of its progression but it may not be necessarily fatal and be reversible if appropriate interventions are rapidly performed.

Adolescent↗

Spinal anaesthesia with midazolam in the rat.

PURPOSE: This study examined in an animal model whether intrathecal midazolam, alone or with fentanyl, can achieve anaesthesia sufficient for laparotomy, comparable to lidocaine. Effects on consciousness and whether anaesthesia was segmental were also examined. The haemodynamic and respiratory changes were compared with those of intrathecal lidocaine or intrathecal fentanyl alone. METHODS: Sixty Wistar strain rats, with nylon catheters chronically implanted in the lumbar subarachnoid theca, were divided into six groups. Group 1 (n = 12) received 75 microL intrathecal lidocaine 2%. Group 2 (n = 12) received 75 microL intrathecal midazolam 0.1%, Group 3 (n = 12) received intrathecal 37.5 microL midazolam 0.1%, plus 37.5 microL fentanyl 0.005%. Group 4 (n = 12) received intrathecal 50 microL fentanyl 0.005%. Group 5 (n = 6) received 75 microL midazolam 0.1% iv. Group 6 (n = 6) received halothane 0.6% in oxygen by inhalation. RESULTS: Both groups that received intrathecal midazolam, alone or combined with fentanyl, developed effective segmental sensory and motor blockade of the hind limbs and abdominal wall, sufficient for a pain-free laparotomy procedure. Neither of these groups, unlike the group that received intrathecal lidocaine, developed a reduction in blood pressure or change in heart rate at the time of maximal sensory or motor blockade, nor were there changes in the arterial blood gases or respiratory rate. CONCLUSION: Midazolam, when injected intrathecally, produces reversible, segmental, spinally mediated antinociception, sufficient to provide balanced anaesthesia for abdominal surgery.

Anesthesia, Spinal↗

Neurotoxicity after spinal anaesthesia induced by serial intrathecal injections of magnesium sulphate. An experimental study in a rat model.

We have previously demonstrated in a rat model that the lumbar intrathecal injection of 0.02 ml 6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, produces a state of spinal anaesthesia and general sedation which reversed completely after 6 h, without evidence of neurotoxicity, immediately or during the week thereafter. Using the same model and five groups of six animals in each, we administered the same volume and concentration of magnesium sulphate and compared its clinical effects with those of 0.02 ml 12.6% magnesium sulphate, 0.02 ml 2% lignocaine and 0.02 ml 0.9% sodium chloride solution, given as a series of 15 injections on alternate days for a period of 1 month. The animals were then killed and their spinal cords and meninges examined histologically. No significant differences were noted in the times of onset, durations of sensory and motor blockade and the times to full recovery throughout the entire period of 1 month's observation in the animals receiving intrathecal 6.3% magnesium sulphate. In the group receiving 12.6% magnesium sulphate, the time of onset of sensory and motor blockade was shorter and the duration of both parameters was significantly longer than in the former group. Full clinical recovery and resumption of normal eating and drinking took place in both groups throughout the entire series of 15 successive intrathecal injections. Identical, mild, uniform histopathological changes in the spinal cord were seen in all the five groups, including the group in which only the intrathecal catheter was implanted. The complete recovery and benign consequences of repeated intrathecal injections of iso-osmolar magnesium sulphate in a rat model indicate a lack of neurotoxicity and provide an impetus for further trials in larger animal species, before initial clinical trials of this substance, given intrathecally, in humans.

Anesthesia, Spinal↗

Serum electrolyte and blood gas changes after intrathecal and intravenous bolus injections of magnesium sulphate. An experimental study in a rat model.

The effect of intrathecally administered magnesium sulphate on serum levels of magnesium, sodium, potassium, calcium and blood gas variables was studied in a rat model. Magnesium sulphate given intrathecally has previously been shown to produce segmental spinal blockade with no permanent neurological damage. The previous studies, however, had not investigated the possible systemic effects of the magnesium sulphate. The serum magnesium level increased significantly at 1 and 2 h after the intrathecal injection of both 6.3% and 12.6% magnesium sulphate (6.3%: 28% at 1 h, 24% at 2 h; 12.6%: 22% at 1 h, 16% at 2 h). These changes were not as great as occurred when the same dose of magnesium sulphate was administered intravenously. In all cases, the serum magnesium had returned to normal by 24 h. There were no significant changes in calcium, sodium or potassium levels, nor in arterial blood gas variables. These results show that intrathecally administered magnesium sulphate has little effect on electrolyte homeostasis.

Anesthesia, Spinal↗

Spinal anaesthesia induced by intrathecal magnesium sulphate.

We have demonstrated in a rat model that the intrathecal injection of 0.02 ml of 6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, will produce a state of spinal anaesthesia and general sedation, lasting approximately 1 h. These effects reversed completely after 6 h, without evidence of neurotoxicity, immediately or during the period 1 week following the injection. The accompanying changes in haemodynamic and respiratory functions were minimal throughout the period of anaesthesia and compare favourably with those induced by an intrathecal bolus of 0.04 ml of 2% lignocaine.

Anesthesia, Spinal↗

Are elevated liver enzymes and bilirubin levels significant after laparoscopic cholecystectomy in the absence of bile duct injury?

OBJECTIVE: Increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels were noted incidentally after a laparoscopic cholecystectomy. The percentage in which such elevation occurs and its clinical significance in the absence of bile duct injury were investigated. SUMMARY BACKGROUND DATA: Bile duct injury is the most feared complication of laparoscopic cholecystectomy. Some laboratory tests may be indicative of this complication, such as increases in liver enzyme (AST, ALT, and alkaline phosphatase [ALP]) and bilirubin. These parameters have not been investigated in patients who had laparoscopic cholecystectomy and in whom no damage to the bile duct was noted. METHODS: Sixty-seven patients with normal results of preoperative liver function test were entered into the study. Blood was collected 24 hours after laparoscopic cholecystectomy, and AST, ALT, ALP, and bilirubin levels were measured. RESULTS: A mean 1.8-fold increase in AST occurred in 73% of patients; 82% showed a 2.2-fold increase in ALT. A statistically nonsignificant increase was noted in 53% of patients (ALP remained within normal limits), and in 14% of patients bilirubin levels were increased (they were primarily of the unconjugated type). CONCLUSIONS: In many patients a significant increase in AST and ALT levels occurred after laparoscopic cholecystectomy, but they returned to normal values within 72 hours. The cause of this is unclear, and these elevations appear to have no clinical significance.

Adult↗

Primary malignant melanoma in the parotid gland.

Reports of primary malignant melanoma arising from the parotid salivary gland are extremely rare and, to date, have been sporadic. We report a pertinent case, and tabulate and correlate the clinical findings of the 13 cases reported thus far in the literature. The most common symptom is a progressively enlarging, asymptomatic, firm, and fixed mass. Total excision has been the established treatment of choice. The contribution of radiotherapy, chemotherapy, and immunotherapy remains unclear, and it is not possible at present to predict the outcome of treatment in individual patients. Although rare, primary malignant melanoma should be considered in the differential diagnosis of parotid tumors. The clinical significance of establishing the diagnosis of primary malignant melanoma of the parotid gland is emphasized.

Adult↗

High-output left ventricular failure after dextran use in an operative hysteroscopy.

High-output left ventricular failure occurred in a patient after a difficult case of hysteroscopic lysis of adhesions using dextran as a distension medium. The excessive dissection in the uterine wall, the long duration of the operation, and the large volumes of dextran probably caused intravasation of dextran into the systemic circulation inducing a significant shift of fluids from the third space. This was possibly assisted by the large volume of fluids given intravenously in a 45-kg patient initiating the reported sequence of events.

Adult↗

Neurological toxicity of the subarachnoid infusion of bupivacaine, lignocaine or 2-chloroprocaine in the rat.

Neurotoxicity after subarachnoid infusion of bupivacaine, lignocaine and 2-chloroprocaine was studied in a chronic rat model. Hartmann's solution 100 microliter h-1 was infused as a control, and 0.5% bupivacaine, 1.5% lignocaine and 2.0% 2-chloroprocaine were infused at 100 microliter h-1 for 3, 6 or 24 h, to five rats in each group. No residual paralysis occurred in the control group, but 27 of 45 rats (60%) which received an infusion of local anaesthetic had residual paralysis lasting until sacrifice at 7 days. The incidence of paralysis was dependent on the duration of exposure to the local anaesthetic, but there were no significant differences in incidence between any of the local anaesthetics tested. Abnormal histology, in the form of neuronal vacuolation, was not a sensitive index, being present in control rats, but more intense in those receiving lignocaine and 2-chloroprocaine than in those given bupivacaine; no correlation with clinical findings could be established. The neurotoxic effects of each local anaesthetic tested as a continuous intrathecal infusion were dose related in the rat, which may be a useful model for screening other local anaesthetics.

Anesthetics, Local↗

Effects of spinal blockade with bupivacaine on parturition in rats.

On the day of expected delivery, primigravid rats received 0.5% bupivacaine continuously through a chronically implanted intrathecal cannula to produce intense sensory and motor blockade below the T10 level. The mean duration of delivery was prolonged to 3.1 h compared with 1.4 h in a control group without intrathecal blockade and a group which received an intrathecal infusion of Hartmann's solution. The mean percentages of live births per litter surviving the first 6 h was 94% in the control groups and 42% in those receiving bupivacaine by intrathecal infusion. No increased perinatal mortality was observed in another control group receiving an i.p. infusion of 0.5% bupivacaine in the same dose as that given intrathecally. Two mother rats died during delivery under spinal blockade because of prolonged labour. It is concluded that, without obstetric intervention, intense sensory and motor blockade delayed parturition and increased fetal mortality in the pregnant rats.

Anesthesia, Spinal↗

Self-administered nalbuphine, morphine and pethidine. Comparison, by intravenous route, following cholecystectomy.

In a double-blind clinical trial of 48 patients, nalbuphine, morphine, and pethidine were compared by on-demand intravenous analgesia during the first 24 hours after cholecystectomy. Overall pain relief (visual analogue score) was recorded by the patients as 50 (SEM 4) for nalbuphine, 44 (SEM 4) for morphine and 53 (SEM 5) for pethidine. These scores were not significantly different. The mean demand for each drug over the 24-hour period was 70 (SEM 12) mg for nalbuphine, 46 (SEM 6) mg for morphine and 614 (SEM 49) mg for pethidine. Pain on movement, either during deep breathing or turning, was found to be less well controlled after nalbuphine (70, SEM 2), and pethidine (67 SEM 7) than after morphine (52, SEM 5; p less than 0.01). The incidence of side effects was similar with each drug. Nalbuphine is a useful postoperative analgesic, as effective as pethidine. Nalbuphine 15 mg is apparently equipotent with morphine 10 mg or pethidine 120 mg by this mode of administration.

Adult↗

Chronic cannulation of the intradural or extradural space in the rat.

An animal preparation has been developed to test therapeutic agents in the extradural and intradural spaces. Under anaesthesia a hole was drilled in the penultimate lumbar vertebra of male Wistar rats and the appropriate space cannulated. The catheter was tunnelled subcutaneously to emerge at the neck. There was no spinal cord or meningeal reaction after 1 month. Catheters remained patent for 3 months. The method of cannulation allowed free rostral spread of drugs. Using plain 2% lignocaine, paralysis and anesthesia of the hind limbs required an intradural volume of 32 +/- 3 mulitre: the required volume on extradural injection was 46 +/- 2 mulitre (P less than 0.01). Paralysis of all limbs required an intradural volume of 115 +/- 12 mulitre. Respiratory arrest and death required a mean intradural volume of 179 +/- 15 mulitre.

Anesthesia, Epidural↗

Differential sensory and motor blockade after spinal cocaine in the rat and marmoset.

Various concentrations of local anaesthetic agents have been injected into the rat and marmoset via a chronically implanted cannula in the subarachnoid space. In the rat, cocaine at a concentration of 0.125% produced analgesia without motor blockade whereas higher concentrations produced motor blockade in some animals. No clear differentiation could be shown with any concentrations of lignocaine or bupivacaine. In the marmoset, 0.125% cocaine resulted in sensory block in four out of five marmosets without motor blockade, whereas 0.25% cocaine produced motor block in two out of four marmosets. It would appear that differential blockade of sensory function without motor loss can be achieved by cocaine. New local anaesthetics based on cocaine or similar chemical structures would seem potentially valuable.

Analgesia↗

Histopathology of the spinal cord after intrathecal cocaine, bupivacaine, lignocaine and adrenaline in the rat.

Repeated intrathecal injections were given through catheters which had been chronically implanted in the subarachnoid space of rats. Injections were made of cocaine 0.25%, 0.125% and 0.0625%; bupivacaine 0.5%; lignocaine 2% and 0.5%; adrenaline 0.01% (1 in 10 000) and 0.002% (1 in 200 000); and sodium chloride 0.9%. Five injections of 35 microliter of each concentration of each drug were given hourly each day for two days to three rats. No clinical nerve damage was detectable in any rat. The only pathological change found in any rat was the development of cytoplasmic vacuolation in the neurones of the anterior and posterior horns. The changes were most prominent after injection of 0.9% sodium chloride and bupivacaine, whilst lignocaine (0.5 and 2%) showed the least number of vacuoles, which were also the smallest in size. Adrenaline and cocaine were intermediate in effect. There was no evidence of cell death. These changes were not seen in control animals in which catheters had been implanted but no injections had been given. The changes were mild and it is concluded that the agents tested caused no significant damage.

Animals↗

Pharmacokinetic evaluation of ICI 35 868 in man. Single induction doses with different rates of injection.

Blood concentrations of ICI 35 868 have been measured in patients following a single bolus dose of 2 mg kg-1. Three different rates of injection of the anaesthetic agent (3-5s, 20s and 40 or 50s) were examined. Pharmacokinetic indices, derived from blood concentrations of ICI 35 868, were independent of the speed of injection. The blood profiles could be described by a two-compartment open model with a mean alpha-phase half-life of 2.5 min and a mean beta-phase half-life of 54.5 min. The mean total body clearance was 3454 ml min-1. Similar data were obtained from a 4-mg kg-1 dose. The mean recovery time (4.4 min) and concentration of ICI 35 868 at awakening (1.05 micrograms ml-1) were also independent of the rate of injection. Using the derived pharmacokinetic model, predictions of drug concentrations have been made for repeated bolus doses, or infusions, of ICI 35 868.

Adolescent↗