Injection Of Midazolam Research Articles

Sedation depends on the level of sensory block induced by spinal anaesthesia

We have investigated the relationship between the extent of spinal block and occurrence of sedation. In a first series of 43 patients, the distribution of sedation score (measured on the Ramsey scale) was related to the extent of spinal block (pinprick). In a second series of 33 patients, the relationship between sedation score and spinal block persisted after injection of midazolam 1 mg. This study confirmed that high spinal block was associated with increased sedation.

Changes in cerebral blood flow velocities associated with radermecker complexes in a patient with subacute sclerosing panencephalitis: A case report

The electroencephalogram (EEG) in subacute sclerosing panencephalitis (SSPE) is characterized by generalized periodic high amplitude complexes recurring at intervals of 4–12 seconds (Radermecker complexes). Little is known about their genesis, although most authors favor a brain stem origin. We wished to study changes in cerebral perfusion associated with these complexes in order to better understand their pathophysiology. We present a 15-year old girl who was diagnosed to have SSPE with cognitive and intellectual decline. Radermecker complexes were first detected on EEG after an injection of midazolam. They occurred spontaneously 2 weeks later. We studied changes in cerebral blood flow velocities (CBFV) measured by transcranial Doppler (TCD) in both middle cerebral arteries (MCA) time-locked to the occurrence of the Radermecker complexes. Averaging 250 Radermecker complexes over five recording sessions demonstrated a biphasic signal with a decrease in CBFV by 5,8%, peaking at 0.7 seconds after the onset of the complexes, and a subsequent increase in CBFV by 3.7% peaking at 3 seconds after the beginning of the complex. Changes in heart beat showed a similar course with an initial decrease and a subsequent increase in frequency. These similar temporal changes between CBFV and heart rate suggest that the pathophysiologic mechanisms of these complexes may also affect the balance of autonomic tone descending from brain to heart.

Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor.

The mammalian gamma-aminobutyric acid type A (GABA(A)) receptor, a likely target of anesthetic action, exhibits remarkable subunit heterogeneity. In vitro expression studies suggest that there is subunit specificity to anesthetic responses at the GABA(A) receptor. The authors tested whether genetically engineered mice that lack the beta3 subunit of the GABA(A) receptor differed in their sensitivities to several general anesthetic agents. Median effective concentrations for loss-of-righting reflex and tail clamp/withdrawal for enflurane and halothane were determined in mice with and without the beta3 gene and gene product. Sleep time was measured after intraperitoneal injection of pentobarbital, ethanol, etomidate, and midazolam. Null allele mice (beta3 -/-) did not differ from wild-type mice (beta3 +/+) in the obtunding response to enflurane and halothane but were significantly more resistant to enflurane (null allele half-effect concentrations [EC50] of 2.59 +/- 0.10 vs. wild-type EC50 of 2.06 +/- 0.12 atm %, P < 0.001) and halothane (null allele EC50 of 1.73 +/- 0.04 vs. wild-type EC50 of 1.59 +/- 0.05 atm %, P = 0.01) as determined by tail clamp response. Wild-type and null allele mice exhibited divergent responses to other sedative agents active at the GABA(A) receptor. No differences were noted in sleep times after administration of pentobarbital and ethanol, but null allele mice were more resistant to etomidate (null allele EC50 of 17.8 +/- 1.9 min vs. wild-type EC50 of 26.2 +/- 2.4 min, P < 0.02) and midazolam (null allele EC50 of 14.2 +/- 7.8 min vs. wild-type EC50 of 41.3 +/- 10.4 min, P < 0.05). The beta3 subunit of the GABA(A) receptor appears to be important in the mediation of the immobilizing (tail clamp) but not obtunding (loss-of-righting reflex) effects of the volatile anesthetic agents enflurane and halothane. These data support the hypotheses that separate components of the anesthetic state are mediated via different central nervous system loci; that the GABA(A) receptor is a likely target for the immobilizing response to volatile anesthetic agents; and that the beta3 subunit plays a direct or indirect role in the mediation of this response. Absence of the beta3 subunit appears to attenuate the obtunding effect of midazolam and etomidate but appears not to alter the obtunding effect of pentobarbital, enflurane, and halothane, suggesting that these anesthetic agents produce hypnosis by different specific molecular mechanisms.

Met-enkephalin alteration in the rat during chronic injection of morphine and/or midazolam

We have recently reported that the short-acting anesthetic and analgesic drug midazolam can produce analgesia and decrease morphine tolerance and dependence in the rat by interacting with the opioid system. This study was designed to investigate the effect of midazolam, morphine, and both together on met-enkephalin levels in the rat. Male Sprague–Dawley rats were divided into four groups: (1) saline-saline; (2) saline-morphine; (3) midazolam-saline, and (4) midazolam-morphine groups. First, a saline or midazolam injection was given intraperitoneally and after 30 min a second injection of saline or morphine was given subcutaneously once daily for 11 days. Animals were sacrificed on the 11th day 60 min after the last injection to measure met-enkephalin by radioimmunoassay. Morphine tolerant animals showed a significant increase in met-enkephalin levels in the cortex (137%) and midbrain (89%), and a significant decrease in met-enkephalin levels in the pituitary (74%), cerebellum (34%) and medulla (72%). Midazolam treated animals showed a significant decrease in met-enkephalin levels in the pituitary (63%), cortex (39%), medulla (58%), kidneys (36%), heart (36%) and adrenals (43%), and a significant increase in met-enkephalin levels in the striatum (54%) and pons (51%). When morphine and midazolam were injected together, midazolam antagonized the increase in met-enkephalin levels in cortex and midbrain region and the decrease in met-enkephalin level in the medulla region observed in morphine tolerant animals. These results indicate that morphine tolerance and dependence is associated with changes in the concentration of met-enkephalin in the brain. Midazolam may inhibit morphine tolerance and dependence by reversing some of the changes induced in met-enkephalin levels in brain by morphine in morphine tolerant and dependent animals.

Histological changes following epidural injection of midazolam in the neonatal rabbit

Midazolam can produce antinociceptive effects when used via intrathecal or epidural routes. Neurotoxicity studies are scanty especially for neonates. The aim of this study was to carry out electron microscopic (EM) examinations in the neonatal rabbit to determine the histological effects of epidural midazolam on spinal cord. Twenty white New Zealand neonatal rabbits were randomly assigned to three groups receiving single dose of 0.9% saline (Group I; Control, n = 4), 0.9% saline titrated to pH = 3.9 by addition of hydrochloric acid (Group II; n = 6), midazolam 250 micrograms.kg-1 (Group III; n = 12) epidurally. Half of each group were sacrificed on the second day and the remainder on the seventh day and spinal cord sections were evaluated by EM. Control group displayed normal histology on grids. Group II and II showed a variable degree of neurotoxic effects such as degeneration of vacuoles, cytoplasm and neurofilaments, disruption of myelin sheaths, lysis of cell membranes, perivascular oedema, pyknosis of nuclei. The toxic effects of acidic saline and midazolam are similar, in view of these results the epidural use of acidic midazolam (commercially available preparations) in neonates should be avoided.

Effects of midazolam on pain sensations in the face

Objectives. This study investigated the effects of midazolam, a sedative, on tactile and pain sensations on the skin of the chin. Study Design. Thirty-seven volunteers were segregated into four groups; the first group was the control group; the second to fourth groups were administered 0.025 mg/kg, 0.05 mg/kg, and 0.075 mg/kg of midazolam, respectively, as a bolus injection. All volunteers reclined in a dental chair for the experiment. Tactile and pain sensations were determined over time after injection of midazolam, the former using von Fray thread, the latter using an esthesiometer. Results. Thresholds of tactile sensitivity and of pain were statistically significantly different from control values at 10 minutes after injection of midazolam in the 0.05 mg/kg group and in the 0.075 mg/kg group. Conclusion. Although 0.025 mg/kg of midazolam produced sedation, at least 0.05 mg/kg of this agent was required to alter the thresholds for perception of tactile and painful stimulation.

Effect of chronic treatment with morphine, midazolam and both together on dynorphin(1–13) levels in the rat

We have recently reported that midazolam, a benzodiazepine receptor agonist that is also a short acting anesthetic and analgesic drug, can produce analgesia and decrease morphine tolerance and dependence in the rat by interacting with the opioidergic system. This study was designed to investigate the chronic effect of midazolam and/or morphine on the levels of dynorphin(1–13) in the pituitary gland, different brain regions, spinal cord and peripheral tissues of the rat. Four sets of animals were used: (I) saline-saline; (II) midazolam (0.03, 0.3 or 3.0 mg/kg, body wt., i.p.)-saline; (III) saline-morphine (10.0 mg/kg, body wt., s.c.); and (IV) midazolam-morphine (0.03, 0.3 or 3.0 mg/kg midazolam+10.0 mg/kg morphine) groups. The first saline or midazolam injection was given i.p. and after 30 min, the second injection of saline or morphine was given s.c. daily for 11 days. Animals were sacrificed on the 11th day, 60 min after the last injection and dynorphin(1–13) was measured in indicated tissues by radioimmunoassay method. The midazolam treated animals showed a significant decrease in dynorphin(1–13) levels in the cortex, cerebellum, cervical region of spinal cord, heart and adrenals, and a significant increase in the hypothalamus, striatum and lumbar region of the spinal cord. The morphine treated animals showed a significant decrease in dynorphin(1–13) levels in the pituitary gland, hypothalamus, hippocampus, striatum, cerebellum, pons, medulla, kidneys, adrenals and spleen, and a significant increase only in the lumbar region of the spinal cord. When both drugs were injected together there was no effect on pituitary gland, kidneys and spleen. These drugs antagonize each other's effect on dynorphin(1–13) in the hypothalamus, striatum, cerebellum, pons, medulla and heart. However, the midazolam-morphine combination significantly increases dynorphin(1–13) levels in the hippocampus, cortex, midbrain, cervical and lumbar regions of the spinal cord, and adrenals. These results suggest the involvement of dynorphin(1–13) in the inhibition of morphine-induced tolerance and dependence by midazolam in the rat. These results may also help us in understanding the intrinsic mechanisms involved in narcotic tolerance and dependence. © 1997 Elsevier Science B.V. All rights reserved.

C- jun mRNA expression in the hippocampal formation induced by restraint stress

The effect of restraint stress on c- jun mRNA expression in the hippocampal formation was investigated by in situ hybridization, dot blot and northern blot. c- jun mRNA expression increased after 60 min of forced restraint in the dentate gyrus, CA1 and CA3 regions of the hippocampal formation. The effect in the dentate gyrus was attenuated by pre-stress i.c.v. injection of the anxiolytic benzodiazepine midazolam (20 nmol/2 μl) or the N-methyl- d-aspartate (NMDA) receptor antagonist 2-amino-7-phosphonoheptanoic acid (AP-7, 5 nmol/2 μl), but not by the 5-HT1A agonist, (±) 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 20 nmol/2 μl). These results suggest that the hippocampal formation is activated during restraint stress, and that this activation is modulated by benzodiazepine/GABA-A or NMDA receptors.©1977 Elsevier Science B.V. All rights reserved.

An investigation of the safety of midazolam use in hospital.

To investigate whether an association exists between midazolam use and serious cardiorespiratory events or death. Retrospective analysis of data in an inpatient record linkage database, collected between March 1986 and October 1987 from 14 hospitals in the United States. A cohort of 19,112 patients who received injectable midazolam or diazepam on the same day that a medical procedure was performed. An attempt was made to identify suspected serious cardiorespiratory adverse events and deaths that occurred within 24 h of study-drug administration. Death rates within 24 h following study-drug administration were compared between patients who received injectable midazolam and those who received injectable diazepam. Validation analysis of the information in the computerized record linkage database indicated that serious cardiac and respiratory adverse events that occurred within 24 h of study-drug administration could not be reliably identified. Therefore, a comparison of the serious cardiorespiratory adverse event rates following administration of midazolam versus diazepam could not be made. Death rates within 24 h of study-drug administration could be evaluated. For the cohort as a whole, the death rate was significantly lower among patients who received midazolam than among those who received diazepam (0.76% versus 1.93%, p<0.01). This difference remained statistically significant, after adjusting for age, sex, comorbidity diagnosis, concomitant drug use, type of medical procedure, and hospital size and teaching capability. The results suggest that there is no increased risk of death associated with midazolam administration when compared to diazepam administration for endoscopic, conscious sedative, and general anesthetic procedures in hospitals.

The effects of midazolam and flumazenil on psychomotor function

To determine the effects of midazolam and its antagonism with flumazenil on psychomotor function as assessed by the perceptive accuracy test (PAT) and choice reaction time (CRT). Double-blind, cross-over, randomized, placebo-controlled study. Department of Anaesthesiology, University Hospital, Linköping, Sweden. 11 healthy volunteers (6 females, 5 males, mean age 32 years). Midazolam 0.1 mg/kg (Group MH), midazolam 0.035 mg/kg (Group ML), or placebo (Group PL) were injected intravenously (IV) in a cross-over design. Flumazenil 0.5 mg was injected after 60 minutes. Plasma concentrations of midazolam were measured at 3, 30, 60 and 75 minutes. Baseline values were first obtained on psychomotor tests including the PAT and CRT. These tests were then repeated 30 and 60 minutes after the IV injection of midazolam or placebo, and repeated 15 and 30 minutes following the injection of flumazenil. A dose-dependent effect of midazolam was seen on the PAT and CRT. Flumazenil completely reversed the psychomotor effects of midazolam in Group ML at 60 minutes but not in Group MH, and this action was clearly detected by the PAT. Psychomotor tests had returned to baseline values when the plasma concentration of midazolam was below 33 ng/ml. A marked inter-individual variation was seen on the PAT, CRT, and in the correlation between the plasma concentration and the results on the PAT. There was a dose-dependent deterioration in psychomotor performance in subjects given midazolam. The PAT was sensitive in the detection of these residual effects, but a large inter-individual variation in the psychomotor effects of midazolam was evident that could be due to pharmacodynamic and pharmacokinetic variability between individuals. Flumazenil in a dose of 0.5 mg IV completely reversed the effects of low-dose, but not high-dose, midazolam.

非線形解析による局所麻酔注射時の生体反応に関する研究

Cardiovascular changes based on real or imaged pain or stress often result from dental treatment. These alterations currently are measured in linear fashion. The new theory of nonlinear dynamic systems predicts that complex physiological systems do not respond in a linear fashion, but may fluctuate, even in short time periods. To test the applicability of this theory to accept dental anesthesia procedures, blood flow waves and volume pulse waves were tested under varing condition of stress. Volunteers were randomly segregated into three groups : One group was tested for emotional stress by suggestion of impending infiltration anesthesia ; at a later time this group was tested for mental stress imposed by a mathematical task. The curves obtained by these two conditions were converted by computer numerical values using the software for nonlinear dynamic analysis (Microsoft Corp.). The second group was tested for emotional responses resulting from anticipation of injection, and from the actual injection itself (1/80, 000 epinephrin containing 2% lidocaine). The third group was tested in the same fashion as the second group, except that they also received an i.v. injection of midazolam five minutes before the start of the testing. The curves obtained from the second and third groups also were converted to numerical values by the aforementioned computer program. The results are summarized as follows : 1. Mental stress imposed by the mathematical task intensifies chaos. 2. Emotional stress by the suggestion of impending local anesthesia intensifies chaos, but is qualitively different from mental stress elicited by the mathematical task. 3. Physical responses to fear and anxiety before injection are more intense than during injection per se. 4. The Lyapunov exponent of blood flow waves reflects emotional stress elicited by suggestion of impending local anesthesia ; the Lyapunov exponent of volume pulse wave reflects physical responses to infiltration anesthesia accompanied by intravenous sedation. 5. Emotional stress of local anesthesia, combined with intravenous sedation produces less chaos than when sedation is omitted as shown by a decline in the Lyapunov exponent. 6. Physical responses without emotional stress result from the purely physical stimulation of infiltration anesthesia without emotional stress. 7. The attractor of mental and physical stress of infiltration anesthesia shows characteristics of confused shape, reduction and disorder toward normal condition.

Nasal benzodiazepines for management of acute childhood seizures?

Spikes were substantially reduced or abolished within 5 to 15 min of injection of midazolam, and control at 165 to 175 min was better than with intravenous diazepam 10 mg, and comparable with intravenous diazepam 15 mg. Sometimes benzodiazepines are given rectally. There are disadvantages in the intravenous, intramuscular, and rectal methods of administration in acute situations. Intravenous injection is often unsuccessful in the small child. Rectal administration may be difficult to arrange in schools, in hostels for respite care, and in the homes of childminders. In addition, absorption from the rectum may be very variable. O’Regan and colleagues 2 have explored the value of intranasal administration. Rather than comparing the nasal with the rectal routes of administration of benzodiazepines as a group, they examined the effectiveness of midazolam given

ミダゾラム（ドルミカム）・ブトルファノール（スタドール）持続注入回路内に析出した結晶成分の分析とその成因

Resolution of the problems appearing in the clinical departments with relation to drug utility is a very important task for hospital pharmacists. The chief nurse of the surgery section recently asked us to examine the crystal material often appearing in the continuous infusion line of Dormicum®-Stadol® (2: 1) several hours after infusion of other medicines. The crystals were examined by high performance liquid chromatography. The retention time of the crystals was the same as that of midazolam, and the crystals were identified to be midazolam. The main cause of the formation of crystals was found to be the rise in the pH of midazolam injection due to the mixing with butorphanol injection. Moreover, the changes in ion strength and ion components in the solution affected the appearance of the crystals. Thus, midazolam should not be infused with butorphanol. If a mixture of midazolam and other medicines must be infused continuously, medical workers should check for the appearance of the crystals.

Hyperphagia induced by direct administration of midazolam into the parabrachial nucleus of the rat

Benzodiazepine receptor agonists increase food intake in many different species, yet there has been little investigation of the central site of actions of these drugs on ingestive behaviour. In the present experiments, direct administration of the benzodiazepine receptor agonist midazolam (3–30 μg/μl) into the parabrachial nucleus of the pons significantly increased the consumption of a wet mash diet and a 3% sucrose solution in adult non-deprived rats. The hyperphagic response was blocked by pre-treatment with the selective benzodiazepine receptor antagonist flumazenil. Injection of midazolam into the parabrachial nucleus had no effect on locomotor activity, despite the fact that in the same animals an increase in mash intake was observed following intra-parabrachial midazolam. These data suggest that benzodiazepine receptors located in the parabrachial nucleus may be an important site of action for the effects of benzodiazepines specifically on ingestive behaviour.

Pharmacokinetics and Pharmacodynamics of Atracurium and its Metabolite Laudanosine in Cardiac Surgery Involving Cardiopulmonary Bypass with Induced Hypothermia

The infusion velocity of the short-acting muscle relaxant atracurium has to be reduced during hypothermic cardiopulmonary bypass to maintain a moderate degree of muscle relaxation. In the present study the extent of neuromuscular blockade and the plasma concentrations of atracurium and its main metabolite, laudanosine, were assayed by high-performance liquid chromatography in 10 patients undergoing open heart surgery for coronary artery bypass. Anaesthesia was induced by an intravenous bolus injection of midazolam (10 to 15mg) and fentanyl (0.75 to 1.5mg). Neuromuscular transmission was monitored at the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve over the wrist (train-of-four). Muscle relaxation was initiated with an intravenous bolus injection of 460 µg/kg atracurium. Waning neuromuscular blockade was enhanced by intravenous injection of constant maintenance doses of atracurium (100 to 200 µg/kg) whenever the first twitch response of a train-of-four (T1) had attained 25% of its control.

Increased food intake following injection of the benzodiazepine receptor agonist midazolam into the IVth ventricle

Despite a prolonged period of research with benzodiazepines, the central site(s) of action for the hyperphagic effects of these compounds remains to be determined. The aim of the present studies was to examine the effect of direct administration of the benzodiazepine receptor agonist midazolam into the IVth ventricle on ingestive behavior in nondeprived rats. In Experiment 1, microinjection of midazolam (3 and 30 μg/μl) into the IVth ventricle was sufficient to increase consumption of a palatable mash. In Experiment 2, the hyperphagic effect was blocked by systemic administration of the selective benzodiazepine receptor antagonist flumazenil (20 mg/kg). The results indicate that a brainstem site of action may be important for the effects of benzodiazepine receptor agonists on ingestive behavior.

Effect of chronic treatment with morphine, midazolam, and both together on beta-endorphin levels in the rat.

We have recently reported that a short-acting anesthetic and analgesic drug midazolam can produce analgesia and decrease morphine tolerance and dependence in the rat by interacting with the opioid system. This study was designed to investigate the effect of midazolam, morphine, and both together on beta-endorphin levels in the rat. Male Sprague-Dawley rats were divided into four groups: (1) saline-saline; (2) saline-morphine; (3) midazolam-saline, and (4) midazolam-morphine groups. First, saline or midazolam injection was given IP and after 30 min a second injection of saline or morphine was given subcutaneously once daily for 11 days. Animals were sacrificed on 11th day 60 min after the last injection, to measure beta-endorphin by radioimmunoassay. Saline-morphine-treated animals showed a significant increase in beta-endorphin levels in the cortex, pons, medulla, lumbar spinal cord, adrenals, and spleen, and a decrease only in its level in pituitary. Midazolam-saline-treated animals showed a significant increase in beta-endorphin levels only in the medulla, and a decrease in its levels in hippocampus, striatum, and adrenals. Saline-morphine-treated animals did not show any changes in plasma beta-endorphin, but animals treated with midazolam-saline had a significant decrease in plasma beta-endorphin. In rats treated with morphine and midazolam together, beta-endorphin levels in cortex, lumbar spinal cord, and spleen decreased to the similar levels observed in rats treated with saline-saline; in pons and cervical spinal cord the levels were even lower than that found in saline-saline group. The decrease in pituitary beta-endorphin in morphine-midazolam-treated rats was due to morphine's own activity, whereas the decrease in plasma beta-endorphin in hippocampus in the morphine-midazolam group was a synergistic effect of morphine and midazolam. The beta-endorphin level in adrenal glands in the morphine-midazolam-treated animals was not different from that found in rats treated with morphine alone but was still higher than that in the saline-saline group. In general, it appears that chronic treatment with morphine stimulates the beta-endorphinergic system. A concomitant treatment with midazolam abolishes the stimulatory effect of morphine on the beta-endorphinergic system. These results may help us in understanding the intrinsic mechanisms involved in narcotic tolerance and dependence.

Evaluation of saccahc eye movements as an objective test of recovery from anaesthesia

Saccadic eye movements have been previously used to assess residual effect of anaesthetics, but this test is seldom compared to other psychomotor tests. The aim of the present study was to validate saccades as a recovery index in relation to frequently referred subjective and psychometric tests. Eight healthy subjects were tested before and after intra-muscular injection of either placebo or 0.15 mg.kg-1 of midazolam. Each session consisted of a saccadic test (recorded by electro-oculography), a choice-reaction-time test (CRT), a subjective state-of-alertness test (11 visual analogic scales) and blood sampling (to monitor midazolam plasma concentration), before and 30 (t30), 60 (t60), 120 (t120), 180 (t180), 240 (t240) minutes after drug administration. In the placebo group, there was no change in subjective assessment, saccade characteristics (latency, peak velocity and duration) or CRT results. In the midazolam group, 6 subjective items changed with different time-courses, when compared to baseline: from t30 to t120 (drowsy, in shape, tired, clumsy, strong) and t120 (woolly). Saccade latency and duration were significantly different from t30 to t120 and until t180 for peak velocity. CRT performance was significantly altered from t30 to t120. Midazolam plasma concentration decreased from 177 +/- 33 ng.ml-1 at t30 to 47 +/- 12 ng.ml-1 at t240. At this latter time, sensorimotor functions returned to the baseline. All subjects fulfilled the clinical conditions for home discharge 4 hours after administration. These results suggest that a saccadic eye movement test is a sensitive and reliable tool for the assessment of residual effect of anaesthetics. This test was found to be more sensitive than CRT test since peak saccadic velocity was the last psychometric parameter to be returned to baseline after midazolam injection. This study also confirms the poor reliability of subjective assessment, as subjects tended to underestimate the alteration of their performance immediately following drug injection.

Midazolam in combination with fentanyl/fluanisone and nitrous oxide as anaesthesia in rabbits--cardiovascular parameters.

When establishing a rabbit model for cardiovascular research in our laboratory we have used midazolam in combination with fentanyl/fluanisone (MFF) and nitrous oxide as anaesthesia. In this study we focused on the effect of the anaesthetic regimen on cardiovascular parameters during open-chest surgery in 12 rabbits. Rabbits were tranquillized by intramuscular injection of fentanyl/fluanisone (0.2 ml/kg of the drug that contained 10 mg/ml fentanyl and 0.2 mg/ml fluanisone). After an intraperitoneal injection of midazolam (4 mg/kg) and additional i.m. injection of fentanyl/fluanisone (0.1 ml/kg) the rabbits were tracheotomized and ventilated on a respirator delivering a gas mixture of 50% N2O, 47.5% O2, and 2.5% CO2. The femoral vein and artery were cannulated and then rabbits received a supply of MFF intravenously. The chest was opened by midline sternotomy and the left ventricle was instrumented with piezo-electric crystals for measurement of regional left ventricular function and with a pressure catheter to measure left ventricular pressure. Radiolabelled microspheres were used to assess cardiac output and left ventricular tissue blood flow. Blood gas analysis showed no difference in the values of pH, pCO2 and pO2 between the open-chest and the closed-chest states. Mean aortic pressure was 74 +/- 4 mmHg in the closed-chest state and 65 +/- 4 mmHg in the open-chest state. Tissue blood flow showed that the left ventricle was well perfused, and mean tissue blood flow values varied between 1.80 and 2.36 ml/min.g. We conclude that the anaesthetic regimen used is easy to control. It is well tolerated in rabbits and is suitable for studies on myocardial contraction in rabbits.

An assessment of resedation following flumazenil-induced antagonism of intravenous midazolam: comparison of psychomotor and amnesic recovery with a non-sedated reference group

The specific benzodiazepine antagonist flumazenil can enhance patient recovery following local anaesthetic day-case surgery performed under sedation. However, in view of its short elimination half-life, concerns have been expressed about the risk of resedation following its use. An open, randomised, parallel group study was designed to explore this question. Eighty-five patients were studied. Group A (n=43) patients underwent local anaesthetic cystoscopy with intravenous (i.v.) midazolam sedation. Following cystoscopy, and 30 min after the injection of midazolam, a bolus dose of flumazenil (0.5 mg i.v.) was given. Group B (n=42) patients underwent no operation and received no drugs but, in all other respects, were treated in an identical fashion to patients in group A. Tests of psychomotor function and memory were administered at baseline and again at 0.5, 1, 2, 3 and 4 h (or equivalent times for group B patients) following the injection of flumazenil. The test results showed no evidence of resedation, but there was evidence of incomplete reversal, as shown by significant differences in critical flicker fusion and delayed word recall at the 0.5-h test point. Group B patients showed no evidence of practice effects but did demonstrate an impairment in test performance possibly related to motivational factors. In conclusion, this study provides no evidence of resedation when using flumazenil to reverse the acute effects of midazolam. Incomplete reversal of amnesia need not delay patient discharge but has important implications with respect to the timing and nature of information imparted to patients prior to their release from hospital.