Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During a nine-month period we have treated 46 patients with status epilepticus with intravenous application of diazepam or midazolam. The initial doze od diazepam was 10 mg (rate: 2-5 mg/min) and of midazolam 15 mg (rate: 5 mg/min). Diazepam was effective in 26 and ineffective in 15 patients. Midazolam stopped status in 4 out of 7 patients. Both drugs were more effective when they were administered at the beginning of status. After the initial termination of status and recovering of consciousness, seizures returned in 10 patients (22%). In the group treated with diazepam, 4 patients had sudden apnea and 6 respiratory depression (totally 10 out of 41). In the group treated with midazolam, 3 had apnea and 2 respiratory depression (totally 5 out of 7). All patients with apnea or respiratory depression received higher doses of both drugs at the higher rates than the others. We conclude that the efficacy of the therapy is moderate while the frequency of serious complications is high. In status epilepticus, where the life of patient is in danger, drugs with such activity are of limited value.
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PMID:[Efficacy of therapy, recurrence of seizures and respiratory complications in the treatment of status epilepticus by intravenous administration of diazepam or midazolam]. 130 8

The purpose of this study was to test the effects of the new beta-carboline ZK 93426 on midazolam-induced cardiorespiratory depression. Seven pentobarbital-anesthetized (35 mg/kg i.p.) cats were treated with intravenous midazolam (2 mg/kg) while monitoring the respiratory minute volume (VE), tidal volume, respiratory rate, blood pressure, heart rate and expired CO2. Midazolam caused significant decreases in VE (p less than 0.05) and blood pressure (p less than 0.05). ZK 93426 (5 mg/kg i.v.) antagonized these effects and produced significant increases in VE and blood pressure that resulted in the return of these variables to premidazolam control values. In 4 animals with morphine-induced respiratory depression, intravenous ZK 93426 failed to antagonize the respiratory effects of morphine. Administration of intravenous ZK 93426 alone to 4 pentobarbital-anesthetized animals also failed to produce significant changes in cardiorespiratory activity. We conclude that ZK 93426 is effective in counteracting the cardiorespiratory depressant effects of midazolam and that these effects appear to be specific. The present data suggest that this compound may be useful for the treatment of benzodiazepine oversedation and overdose.
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PMID:A beta-carboline derivative (ZK 93426) counteracts the cardiorespiratory depressant effects of intravenous midazolam. 150 67

The effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial stimulation (tc-MERs) were studied in five healthy human volunteers. Each subject, in four separate sessions, received intravenous bolus doses of propofol 2 mg.kg-1, etomidate 0.3 mg.kg-1, midazolam 0.05 mg.kg-1, and fentanyl 3 micrograms.kg-1. Electrical tc-MERs (tce-MERs) were elicited with anodal stimuli of 500-700 V. Magnetic tc-MERs (tcmag-MERs) were elicited using a Cadwell MES-10 magnetic stimulator at maximum output. Compound muscle action potentials were recorded from the tibialis anterior muscle. Duplicate tce-MERs and tcmag-MERs were recorded before and up to 30 min after drug injection. Reproducible baseline tce-MERs (amplitude 4.7 +/- 0.43 (SEM) mV, latency 29.4 +/- 0.35 ms) and tcmag-MERs (amplitude 3.7 +/- 0.43 mV, latency 31.1 +/- 0.39 ms) were obtained in all subjects. Pronounced depression of tce-MER amplitude to 2% of baseline values (P less than 0.01) was observed 2 min after injection of propofol. Thirty minutes after injection of propofol, amplitude depression to 44% of baseline (P less than 0.05) was still present, despite an apparent lack of sedation. Midazolam caused significant (P less than 0.01) amplitude depression, e.g., tcmag-MER to 16% of baseline values 5 min after injection. Significant depression persisted throughout the 30-min study period. Fentanyl did not cause any statistically significant amplitude changes in this small population. Etomidate caused significant but transient depression of tc-MER amplitude. However, there was considerable intersubject variability. Latency did not change significantly after any drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans. 155 Feb 74

We have evaluated the analgesic effect of continuous intrathecal administration of midazolam in 4 patients using a three-level score (no change, amelioration, and marked improvement). The secondary effects of this drug were also investigated (sedation, nausea, vomiting, respiratory depression, urinary retention, motor dysfunction). In one patient midazolam was the only drug administered, whereas in three patients this drug was associated with morphine. In one patient with a peripheral arteriopathy, midazolam at a dose of 12 mg/day was unable to equal the analgesic effect achieved with 0.4 mg of morphine. The remaining three patients had carcinoma and received a continuous intrathecal perfusion of morphine at increasing daily doses up to 12; 4,8; and 6 mg/day, respectively without pain relief. In these patients the association of midazolam at respective doses of 9; 4-8; and 6 mg/day induced amelioration in one patient and marked improvement in the two other patients. Midazolam did not change the heart rate, respiratory rate, arterial blood pressure, nor body temperature. We believe that the analgesic effect of intrathecal administration of midazolam is due to its coupling with the ionophore complex GABA-spinal benzodiazepine that in turn produces an increment of the GABA amino butyric acid at this level.
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PMID:[Intrathecal administration of morphine, midazolam, and their combination in 4 patients with chronic pain]. 159 51

Flumazenil, a benzodiazepine antagonist, reliably reverses midazolam-induced sedation; however, its effect on respiratory depression has not been established completely. Twelve healthy volunteers received sufficient midazolam (0.13 +/- 0.01 mg.kg-1 mean +/- SE) to render them unresponsive to verbal command; they then received flumazenil 1.0 mg or placebo (flumazenil vehicle) in a randomized, double-blind fashion. Ventilatory drive was measured before and after administration of midazolam, as well as 3, 30, 60, and 120 min after administration of flumazenil or placebo. Seven to 30 days later, the study was repeated, with subjects receiving placebo or flumazenil (whichever they had not received during their first trial). Midazolam caused significant decreases in the slope of the CO2 response (-29 +/- 5%; P less than 0.005); minute ventilation (VE) at end-tidal CO2 tension (PETCO2) = 46 mmHg (-28 +/- 4%; P less than 0.001), and tidal volume at PETCO2 = 46 mmHg (-44 +/- 4%; P less than 0.005). Three minutes after intravenous administration of flumazenil 1.0 mg, VE46 and tidal volume increased to 108 +/- 6% and 105 +/- 6%, respectively, of their premidazolam values; at the same time after administration of placebo, VE46 and tidal volume remained significantly depressed (between groups, P less than 0.005 for each variable). Thirty minutes later, these variables did not differ between groups, probably because the effects of flumazenil and midazolam were diminishing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Flumazenil antagonism of midazolam-induced ventilatory depression. 185 5

Upper gastrointestinal endoscopy can be performed without intravenous sedation but the evidence suggests that, in the United Kingdom and United States, most patients and endoscopists prefer that some form of premedication is given. Intravenous diazepam or midazolam are used by the majority of endoscopists. In the UK, the ratio of diazepam to midazolam users is approximately 2:1, while in the USA more endoscopists are now using midazolam. Midazolam is approximately twice as potent as diazepam but, when allowance is made for this, there is probably little or no difference in the propensity of the two drugs to produce respiratory depression. The antegrade amnesic effect of midazolam is significantly superior to that of diazepam. A benzodiazepine/narcotic combination can achieve a smoother and more rapid induction with less gagging and choking, but the incidence of adverse outcomes--particularly respiratory depression--is increased significantly. Over 50% of the deaths that are associated with upper gastrointestinal endoscopy are due to cardiopulmonary problems. Hypoxia is very common if measured using non-invasive monitoring equipment, such as a pulse oximeter. Methods of preventing oxygen desaturation and thus, by inference, most cardiac arrhythmias associated with endoscopy are discussed, as is the role of flumazenil, the new benzodiazepine antagonist.
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PMID:Review article: premedication and intravenous sedation for upper gastrointestinal endoscopy. 210 78

Generalized tonic-clonic seizures are a neurologic emergency. Duration of ictal activity has been associated with neurologic sequelae. The purpose of this study was to determine if midazolam, a short-acting benzodiazepine, could effectively ablate ictal activity in an animal model without significant cardiorespiratory compromise. Ten domestic swine (10 to 20 kg) were ventilated and hemodynamically monitored. Bifrontal craniotomies were performed and electrocortical activity was recorded throughout the experiment. Pentylenetetrazol (100 mg/kg) was administered iv to induce seizures. Midazolam (0.1 mg/kg) was administered iv and serum levels were drawn at 1, 2, 5, 10, 15, and 20 min after administration. There was no significant difference between the baseline and postmidazolam vital signs. Seizure activity was seen periodically as generalized spikes, as well as individual spikes for 29 +/- 5 sec after midazolam administration. A period of attenuation of 24 +/- 7 sec was seen before returning to baseline electrocortical activity. Our study demonstrates that midazolam effectively ablated induced ictal activity without significant cardiorespiratory depression and with similar EEG effect as other benzodiazepines.
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PMID:Intravenous midazolam suppression of pentylenetetrazol-induced epileptogenic activity in a porcine model. 210 74

Intravenous midazolam was given to 17 patients coming to upper G.I. endoscopy. All patients had an ear oximeter and calibrated induction plethysmograph attached to record oxygen saturation and minute volume continuously. Midazolam induced significant depression of respiration. Following removal of the endoscope, a new base line was obtained before giving intravenous flumazenil in an attempt to reverse the sedative and ventilatory effects of midazolam. When 0.5 mg of flumazenil was given over 20 s, followed by 0.1 mg every minute, up to a total of 1.0 mg, all patients were apparently awake in under 2 min. Although the flumazenil had clearly reversed the sedative effects of midazolam, the ventilatory effects were largely uninfluenced. The implications are discussed.
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PMID:Speed of reversal of midazolam-induced respiratory depression by flumazenil--a study in patients undergoing upper G.I. endoscopy. 210 71

Of the numerous benzodiazepines currently available, only a few are used in anaesthetic practice. Midazolam is utilised as a premedicant, sedative, and an induction agent and produces minimal depression of ventilation or of the cardiovascular system. The anticonvulsant activity is similar to that of diazepam. In neuroanaesthesia midazolam may be an acceptable alternative to other intravenous induction agents like barbiturates or etomidate in patients with compromised intracranial compliance. Midazolam produces dose-related reductions in cerebral blood flow and cerebral oxygen consumption. However, midazolam does not necessarily prevent increases in intracranial pressure during induction of anaesthesia. In the electroencephalogram (EEG) midazolam produces a reduction in alpha-activity, an increase in theta-delta-activity and low-voltage beta-activity. Midazolam like other benzodiazepines does not affect early components of auditory and somatosensory evoked responses, whereas late cortical responses may be suppressed. Flumazenil, a specific benzodiazepine antagonist, has been demonstrated to be effective in reversing benzodiazepine-induced sedation. In the EEG midazolam-induced changes vanish almost instantaneously. Flumazenil is also effective in restoring the amplitudes of cortical auditory and somatosensory evoked responses. However, as has been demonstrated in head-injured patients and animal experiments after incomplete cerebral ischaemia, increases in cerebral blood flow and intracranial pressure cannot be excluded after flumazenil administration. When utilising flumazenil for wake-up procedures in midazolam-sedated patients with pathological intracranial compliance, flumazenil has to be titrated very carefully in low doses over prolonged periods.
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PMID:Midazolam and flumazenil in neuroanaesthesia. 210 78

More than 80 deaths have occurred after the use of midazolam (Versed), often in combination with opioids, to sedate patients undergoing various medical and surgical procedures. We investigated the respiratory effects of midazolam (0.05 mg.kg-1) and fentanyl (2.0 micrograms.kg-1) in volunteers. The incidence of hypoxemia (oxyhemoglobin saturation less than 90%) and apnea (no spontaneous respiratory effort for 15 s) and the ventilatory response to carbon dioxide were evaluated. Midazolam alone produced no significant respiratory effects. Fentanyl alone produced hypoxemia in half of the subjects and significant depression of the ventilatory response to CO2, but did not produce apnea. Midazolam and fentanyl in combination significantly increased the incidence of hypoxemia (11 of 12 subjects) and apnea (6 of 12 subjects), but did not depress the ventilatory response to CO2 more than did fentanyl alone. Adverse reactions linked to midazolam and reported to the Department of Health and Human Services highlight apnea- and hypoxia-related problems as among the most frequent adverse reactions. Seventy-eight per cent of the deaths associated with midazolam were respiratory in nature, and in 57% an opioid had also been administered. All but three of the deaths associated with the use of midazolam occurred in patients unattended by anesthesia personnel. We conclude that combining midazolam with fentanyl or other opioids produces a potent drug interaction that places patients at a high risk for hypoxemia and apnea. Adequate precautions, including monitoring of patient oxygenation with pulse oximetry, the administration of supplemental oxygen, and the availability of persons skilled in airway management are recommended when benzodiazepines are administered in combination with opioids.
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PMID:Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. 212 73


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