Midazolam respiratory

Midazolam and diazepam decrease arterial pressure without a change ia heart rate. Like thiopeatoae, midazolam is a respiratory depressant. Advantages of midazolam are its amnestic effect, coupled with less postoperative depression (102). A reversal agent for the benzodiazepiaes has also become available. Flumazenil [78755-81-4] C25H24FN2O2, (5) displaces the beazodiazepiaes from their receptor but has Httie demoastrable activity of its owa (103,104). 

Midazolam Midazolam is water-soluble and can be administered intravenously, intramuscularly,13 buccally,14,15 and nasally.16,17 At physiologic pH, it becomes more lipophilic and can diffuse into the CNS. Compared to diazepam and lorazepam, it has fewer effects on the respiratory and cardiovascular systems. Its short half-life requires that it be re-dosed... 

Do not administer concurrently with cisapride, midazolam, triazolam, or ergot derivatives. Competition for CYP3A4 by efavirenz could result in inhibition of metabolism of these drugs and create the potential for serious or life-threatening adverse events (eg, cardiac arrhythmias, prolonged sedation, respiratory depression see Drug Interactions). 

Clinical features of weakness, ataxia, drowsiness, and short-term memory loss can be seen within 30-60 minutes. Coma and respiratory depression are rare but can occur with the ultrashort-acting agents like triazolam and midazolam. Diagnosis is made from the patient history. 

Contraindications Concomitant use of ergot derivatives (causes peripheral ischemia of extremities and vasospasm), flecainide, midazolam, pimozide, propafenone (increases the risk of serious cardiac arrhythmias), or triazolam (increases sedation or respiratory depression) hypersensitivity to lopinavir or ritonavir... 

Given intravenously, both diazepam and midazolam are effective first-line treatments for status epilepticus. It is essential to be aware that the large doses that may be necessary to control convulsions are likely to cause respiratory depression and obtund protective reflexes. Oxygen and equipment suitable for its administration should be available. For intractable status epilepticus, clonazepam is a longer-acting alternative which can also be given by intravenous infusion. Overdosage... 

Benzodiazepines—including diazepam, lorazepam, and midazolam—are used intravenously in anesthesia (see Chapter 25), often in combination with other agents. Not surprisingly, benzodiazepines given in large doses as adjuncts to general anesthetics may contribute to a persistent postanesthetic respiratory depression. This is probably related to their relatively long half-lives and the formation of active metabolites. However, such depressant actions of the benzodiazepines are usually reversible with flumazenil. 

In addition to treating anxiety and insomnia, intravenous BZDs are used as a sedating agent in outpatient surgical procedures. The most commonly used BZD for this indication is the short-acting agent midazolam (Versed). There is a lower potential for respiratory suppression with midazolam than with the barbiturates. 

Sedation Avoidance of doses inducing respiratory sedation and hypotension is recommended Agents such as midazolam with a rapid onset and offset of action are preferred... 

Respiratory depression has been reported as the commonest adverse effect of intravenous diazepam (56), especially at the extremes of age. Midazolam has similar effects (62). All benzodiazepines can cause respiratory depression, particularly in bronchitic patients, through drowsiness and reduction in exercise tolerance (63). Rectal administration of, for example, diazepam can offer advantages in unconscious or uncooperative patients, and is less likely than parenteral administration to produce respiratory depression. 

The safety of benzodiazepines in neonates has been assessed in a retrospective chart review of 63 infants who received benzodiazepines (lorazepam and/or midazolam) as sedatives or anticonvulsants (57). Five infants had hypotension and three had respiratory depression. In all cases of respiratory depression, ventilatory support was initiated or increased. Significant hypotension was treated with positive inotropic drugs in two cases. Thus, respiratory depression and hypotension are relatively common when benzodiazepines are prescribed in these patients. However, both depression and hypotension could also have been due to the severe underlying illnesses and concomitant medications. Matched controls were not studied. 

Diazepam produces less sedation in cigarette smokers, and higher (not lower, as stated in SEDA-20) doses may be required for the same sedative or anxiolytic effect. Owing in part to its continued widespread use, several unusual adverse effects of diazepam continue to be reported. These include cases of urinary retention and compartment syndrome, which are not explicable by its pharmacology. On the other hand, accumulation of diazepam and attendant complications of obtundation and respiratory depression may be understood in terms of its long half-life, particularly in elderly people and medically ill patients. Caution about the intravenous use of diazepam comes from a study that showed cardiac dysrhythmias (mainly ventricular extra beats) in a quarter of oral surgery patients midazolam and lorazepam were much safer (1). 

Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.3 mg/kg have been compared in a prospective randomized study in 47 children (aged 6 months to 5 years) with febrile seizures that lasted over 10 minutes (9). Intranasal midazolam controlled seizures significantly earlier than intravenous diazepam. None of the children had respiratory distress, bradycardia, or other adverse... 

In a randomized study in 301 agitated or aggressive patients, intramuscular midazolam was more rapidly sedating than a mixture of haloperidol + promethazine (12). There was only one important adverse event, transient respiratory depression, in one of the 151 patients who were given midazolam. 

In 27 children with refractory generalized convulsive status epilepticus, midazolam 0.2 mg/kg as a bolus followed by 1-5 (mean 3.1) micrograms/kg/minute as a continuous infusion achieved complete control of seizures in 26 children within 65 minutes (14). There were no adverse effects, such as hypotension, bradycardia, or respiratory depression. In one patient with acute meningoencephalitis, status epilepticus could not be controlled. Five patients died of the primary disorders, one with progressive encephalopathy. 

Midazolam depresses both cardiovascular and respiratory function, especially in elderly patients (20). As little as 0.01 mg/kg can obtund the response to hypoxia and hypercapnia (21). The simultaneous use of opiates (such as fentanyl) commonly produces hypoxia (22). 

Several adverse effects have been reported with the combined use of fentanyl and midazolam, including chest wall rigidity, making ventilation with a bag and mask impossible (SEDA-16, 79). In neonates, hypotension can occur (SEDA-16, 80), and respiratory arrest in a child and sudden cardiac arrest have been reported (SEDA-16, 80). However, in one study there were no cardiac electrophy-siological effects of midazolam combined with fentanyl in subjects undergoing cardiac electrophysiological studies (SEDA-18, 80). 

Midazolam should only be used in an environment in which the patient can be closely monitored (e.g., hospital) because of fhe risk of respiratory depression and respiratory arrest... 

Avoid imnecessary stimulation, which may induce rigidity and spasms. The primary treatment for spasms and rigidity is sedation with a benzodiazepine, such as midazolam or diazepam. Additional sedation may be provided with propofol or a phenothiazine, usually chlorpromazine. In severe disease prolonged spasms and respiratory dys-fimction will necessitate tracheal intubation and mechanical ventilation will be required. If the patient has been intubated and sedation alone is inadequate to control spasms, a neuromuscular blocking drug, e.g., intermittent doses of pancuronium or a continuous infusion of atracurium, will be required. 

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