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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Midazolam and etomidate have been shown to depress cerebral metabolism and may protect the brain during ischemia. However, it has been reported that etomidate may produce EEG spiking activity and seizures, which could adversely affect outcome. We compared the effects of midazolam and etomidate on EEG, cerebral blood flow (CBF), and cerebral cortical oxygen consumption (CMRO2) as well as neurologic outcome following incomplete cerebral ischemia in the rat. CBF was measured with radioactive microspheres and cortical CMRO2 was calculated by multiplying cortical CBF by the arterial-sagittal sinus oxygen content. Incomplete ischemia was produced by unilateral carotid artery occlusion combined with hemorrhagic hypotension. In low doses (0.02 mg/kg/min i.v.), both midazolam and etomidate depressed EEG, decreased CMRO2, and improved outcome from ischemia compared to nitrous oxide control rats. At a higher dose (0.2 mg/kg/min i.v.), midazolam further depressed EEG and CMRO2 and again improved outcome compared to N2O controls. In contrast, high dose etomidate (0.2 mg/kg/min) produced spiking EEG activity without further depression of CMRO2 and a worsening of outcome following cerebral ischemia. These results support previous reports that midazolam and etomidate may protect the brain from incomplete cerebral ischemia but suggest that EEG spiking activity associated with high dose etomidate may be associated with a worse outcome.
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PMID:Cerebral metabolic depression and brain protection produced by midazolam and etomidate in the rat. 1581 35

Benzodiazepine poisoning causes coma and respiratory depression. Our objective was to determine whether, and to what extent, arterial blood gas disturbances correlated with blood or cerebral kinetics of midazolam. A 160 mgkg(-1) single dose of midazolam was infused intravenously over 20 min in catheterized male Sprague-Dawley rats. Midazolam kinetics was simultaneously determined in plasma and brain using striatal microdialysis. Midazolam concentrations were measured using a high-performance liquid chromatographic assay with ultraviolet detection. Midazolam (160 mgkg(-1)) reproducibly induced deep coma with respiratory acidosis. Plasma midazolam kinetics was well described by a bi-exponential model, with an elimination half-life of 6.4+/-1.8 h. The striatal dialysate concentration peaked at 50.0+/-8.9 min after the end of infusion, with a significant delay to peak concentration compared to plasma. Respiratory depression, assessed by the elevation in PaCO2, was more closely correlated with midazolam striatal dialysate rather than plasma kinetics. These results suggest a central mechanism for midazolam respiratory effects at toxic doses in rats. In conclusion, our study showed a delayed onset in peak PaCO2 and pH effects after the slow infusion of a toxic dose of midazolam in rats. The effects on arterial blood gases were better correlated with midazolam striatal concentrations than with plasma concentrations. This study may contribute to better understanding of benzodiazepine-induced respiratory depression in poisonings.
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PMID:Cerebral and plasma kinetics of a high dose of midazolam and correlations with its respiratory effects in rats. 1591 73

Many patients in the ICU receive mechanical ventilation and require sedative medications. Anxiolysis, hypnosis, and amnesia can be considered the primary objects of sedative therapy. Intravenous benzodiazepines are the drugs most commonly used for sedation in ICU. Proper choice and use of benzodiazepines is based on knowledge of the pharmacology and is an essential component of caring for patients in the intensive care unit. Three benzodiazepines--Diazepam, Lorazepam and Midazolam--are currently available for parenteral use in the ICU. Onset and duration of action are determined by their lipid solubility. Respiratory depression and hypotension are dose-dependent. Midazolam is generally preferred to other benzodiazepines in most ICU. It has the shortest half-life of the benzodiazepines, does not have active metabolites, is water soluble and can be administered by continuous infusion. Despite the relatively short half-life of Midazolam, extensive distribution can cause prolonged sedation. Recovery time is proportional to the infusion's duration. Lorazepam is lipid soluble and dissolved in a propylene glycol carrier, produces a delayed onset and prolonged duration of effect and is preferred for long-term sedation (>48 hours). Propylene glycol toxicity is possible with high-dose or prolonged infusions. Diazepam has become less used with the introduction of the shorter-acting and less irritating benzodiazepine. The recent literature focuses on the differences between Midazolam and Propofol, the most used sedatives in ICU, their sequential use and combination. Relevant studies have been performed about propylene glycol toxicity.
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PMID:Sedation in PACU: the role of benzodiazepines. 1630 52

Midazolam is a short-acting benzodiazepine commonly used for conscious sedation for a variety of procedures. Severe adverse reactions, including respiratory depression, respiratory arrest, and anaphylactoid reaction, have been described by manufacturers. We report a patient who developed facial edema after iv injection of midazolam during caesarian section. A 26-year-old woman with a history of atopy and pollen allergy was scheduled for caesarian section. Spinal anesthesia was induced with bupivacaine without significant medical problems. Shortly after receiving 2 mg of iv midazolam 15 minutes after delivery for conscious sedation, she developed pruritus and severe facial edema. Airway obstruction did not occur and no specific medical treatment was necessary. However she was not able to open her eyes for 8 hours because of severe eyelid swelling. We should be more careful in administering midazolam which is generally regarded as safe and well tolerated.
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PMID:[Facial edema and pruritus after intravenous injection of midazolam]. 1644 Jul 13

Nociceptive stimuli are modulated at the dorsal horn of the spinal cord. This modulation is performed by various systems working independently complementarily, additively or supra-additively. Non-opioid analgesics relieve pain without a motor blockade. In contrast to spinal opioids a reduced risk of respiratory depression is expected. In the therapy of chronic pain non-opioid analgesics may be an alternative, given alone or in combination with an opioid. Clinically relevant dosages for antinociception mediated by the alphaadrenoceptoragonistclonidine are >/=150 mug epidurally. Clonidine is effective in reducing acute and chronic pain. In combination with opioids the action of the opioids is intensified. Clonidine intensifies and prolongs the action of local anesthetics. If opioid tolerance occurs, epidural clonidine alone or in combination with an opioid has good antinociceptive action.Midazolam, a water-soluble benzodiazepine, was injected spinally for the reduction of pain for various indications (postoperative, malignancy, chronic back pain, spinal spasticity). Spinal benzodiazepine should not be injected into the spine in patients until it has been proven that there are no neurotoxic effects. Intrathecally injectedbaclofen is a well-known means of reducing spinal spasticity. Used in this way, it may have a secondary analgesic effect. No significant direct analgesic effect has so far been demonstrated. Spinalcalcitonin often leads to insufficient pain relief when given alone. Combination with an opioid may reduce the dosage of the opioid. Nausea and vomiting are frequent side effects of spinal calcitonin. Intrathecalsomatostatin produces antinociception. However, in animal studies neurotoxic action has been observed. Administration in man has not yet been proved to be safe. Spinalketamine has procluted controversial results in clinical studies, and has not yet been excluded that the substance is not neurotoxic.Lysine acetylsalicylic acid (L-ASA) has been given intrathecally for the therapy of severe cancer pain and chronic back pain. In most patients good analgesia was observed up to 2 months after a single injection. If neurotoxity can be excluded, L-ASA may be an alternative in the therapy of cancer pain before neurodestructive therapy is done.
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PMID:[Intrathecal and epidural administration of non-opioid analgesics in acute and chronic pain treatment.]. 1841 40

The purpose of the study was to present recommendations, relevant to the management of neonates and infants aged 0-1 years, treated in intensive care settings. They include general principles and recommendations for pain and sedation assessment, sedation and pain management and advice on the use of pharmacological strategies. The bolus (on demand) administration of sedative agents should be avoided because of increased risk of cardiovascular depression and/or neurological complications. Midazolam administration time should be limited to 72 hours because of tachyphylaxis, and the possibility of development of a withdrawal syndrome and neurological complications (grade A, LOE 1b). The level of sedation and pain should be regularly assessed and documented, using presented scales; the COMFORT scale is preferred. Opioids, given in continuous infusion, are the drugs of choice for neonatal sedation. To avoid withdrawal syndrome, the total doses and time of administration of sedative agents should be limited. Methadone is a drug of choice in the treatment of a withdrawal (Grade B, LOE 2). Intravenous ketamine is recommended, when short-term sedation/anaesthesia is required (Grade C, LOE 3) for painful and/or stressful intensive care procedures. (Grade C, LOE 2). Muscle relaxants should be used for endotracheal intubation and in the situations when mechanical ventilation is not possible due to maximal respiratory effort of the patient.
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PMID:[Recommendations for analgesia and sedation in neonatal intensive care]. 1947 Oct 72

Patient-controlled sedation was utilized in patients aged 15 to 85 yr who were undergoing surgery under local or regional anesthesia. Midazolam, propofol, and methohexitone were used, either by themselves or in combination with fentanyl or alfentanil. Sedation was mild to moderate in the majority of patients, and operating conditions were good. The sedation method provided patients the ability to control the sedation and to vary the degree of sedation according to the environment and to the stress of the procedure. Sedation of the elderly, which tends to be problematic, was made easy using this method, and the elderly patients appeared to enjoy the option. The problems encountered were oversedation, respiratory depression, pain during injection, and postural hypotension.
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PMID:Patient-controlled sedation. 1959 17

Midazolam is a short acting benzodiazepine that has been used for electroconvulsive therapy (ECT) anesthesia. The purpose of this study was to determine whether midazolam used for this purpose would impair the antidepressive efficacy of ECT. In a double-blind random-assignment study midazolam was compared to methohexital on the antidepressive efficacy of bilateral ECT as measured by the reduction in the Montgomery Asberg Depression Rating Scale (MADRS) scores and seizure duration. Sixteen DSM-III-R major depressive disorder patients with melancholia were included. Midazolam and methohexital did not differ in their effects on the MADRS score or seizure duration; no correlation was found between seizure duration and outcome of depression for either group. Our preliminary findings do not support the claim that benzodiazepines should not be used during bilateral ECT.
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PMID:Use of midazolam for ECT anesthesia: effects on antidepressive efficacy and seizure duration. Preliminary findings. 1969 59

Sedation for gastrointestinal endoscopies is obtained by opioids, benzodiazepines, propofol, ketamine and/or droperidol. The pharmacokinetic profile of some sedatives/anesthetics renders them advantageous over others. Opioids, mainly pethidine and fentanyl, are the most popular. Though newer opioids provide a faster recovery, fentanyl is safe and advantageous due to its lower cost. Remifentanil, due to its pharmacokinetic profile (elimination half-life: 9 min), is advantageous for ambulatory patients, though it is not known whether the high cost compensates the benefits. Midazolam is the benzodiazepine of choice as it has a shorter duration of action and a better pharmacokinetic profile than diazepam. Propofol, an intravenous anesthetic, has become very popular for gastrointestinal endoscopies in sedative doses. The opioid and benzodiazepine antagonists, naloxone and flumazenil, are indicated only in particular circumstances, like deep sedation with threatening respiratory depression. Ketamine and droperidol are not popular agents for sedation in the modern endoscopic practice.
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PMID:Pharmacology of sedation agents and reversal agents. 2040 49

Midazolam in an autoinjector was evaluated in an open-label dose escalation study involving 39 healthy participants. Safety and pharmacokinetic parameters were determined for doses ranging from 5 to 30 mg. No serious adverse events were noted during the study. Two participants (30 mg) experienced changes in their electrocardiogram (trigeminy and prolongation of QRS complex) that met the criteria for dose-limiting adverse events. No significant respiratory depression was noted during the study. The midazolam doses studied exhibited a median t(max) of 0.5 hours with a geometric mean terminal elimination half-life value of 4.1 hours (range, 2.9-4.5 hours). The extent of systemic exposure, assessed by area under the curve (AUC) and maximum concentration (C(max)), tended to increase proportionally with increasing doses from 5 to 30 mg; however, for the male 30-mg group, there was evidence of a larger than proportional increase in AUC.
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PMID:Human safety and pharmacokinetic study of intramuscular midazolam administered by autoinjector. 2046 72


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