Agitation midazolam

Severe withdrawal symptoms, including insomnia, irritability, agitation, withdrawal seizures, and delirium, have been described in both mice and humans chronically exposed to the anesthetics nitrous oxide, ether, and isoflurane (Arnold et al. 1993 Delteil et al. 1974 Deniker et al. 1972 Harper et al. 1980 Smith et al. 1979 Tobias 2000). These symptoms were controlled with the administration of y-aminobutyric acid (GABA)-ergic agents such as pentobarbital, midazolam, and diazepam (Arnold et al. 1993 Hughes et al. 1993). 

Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Ann Emerg Med 2006 47 61-67. 

Martel M, Sterzinger A, Miner J, et al. Management of acute undifferentiated agitation in the emergency department a randomized double-blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005 12 1167-1172. 

Midazolam. Intramuscular midazolam, another BZD with reliable parenteral absorption, has produced rapid sedation in acutely psychotic patients with marked agitation (176, 177). 

Midazolam has also been used as an effective medication in palliative medicine when symptom management supersedes the problem of side effects (372, 373). It is used for a variety of indications, including for terminal agitation, for muscle relaxation, and as an anticonvulsant. Recommended therapy is a loading... 

In the management of anxiety, the cumulative effects of longer half-life BZDs often result in excessive sleepiness, apathetic states, and confusion (with or without paradoxical agitation). Thus, short- and intermediate-acting agents such as oxazepam, lorazepam, and alprazolam are preferable. Lower doses (e g., 0.5 to 1.0 mg of lorazepam 0.25 to 0.5 mg of alprazolam) are preferable. Agents with very short half-lives, such as midazolam and triazolam, are not well tolerated, especially in those with more severe neurocognitive disruption. In this context, low-dose antipsychotics were found more effective than lorazepam in the treatment of AIDS-related delirium (495). 

Diazepam, lorazepam, and midazolam are used for preanesthetic medication and as adjuvants during surgical procedures performed under local anesthesia. As a result of their sedative, anxiolytic, and amnestic properties, and their ability to control acute agitation, these compounds are considered to be the drugs of choice for premedication. (The basic pharmacology of benzodiazepines is discussed in Chapter 22.) Diazepam and lorazepam are not water-soluble, and their intravenous use necessitates nonaqueous vehicles, which cause pain and local irritation. Midazolam is water-soluble and is the benzodiazepine of choice for parenteral administration. It is important that the drug becomes lipid-soluble at physiologic pH and can readily cross the blood-brain barrier to produce its central effects. 

A 43 year old man was premedicated for endoscopy with intravenous midazolam 2 mg and pethidine 50 mg). He immediately became agitated and restless. His blood pressure rose to 180/100 mmHg, he sweated, had widely dilated pupils, and had diarrhea. Over the next 90 minutes his condition remitted without specific treatment. He then reported that he had been taking fluoxetine (20 mg every other day), which he had stopped taken about 2 weeks before. 

A 41-year-old woman, with liver lacerations, rib fractures, and pneumothorax after a motor vehicle accident, was given haloperidol for agitation on day 7. During the first 24 hours she received a cumulative intravenous dose of 15 mg, 70 mg on day 2, 190 mg on day 3,160 mg on days 4 and 5, and 320 mg on day 6. An hour after the first dose of 80 mg on day 7, she had ventricular extra beats followed by 5-beat and 22-beat runs of ventricular tachycardia. The rhythm strips were consistent with polymorphous ventricular tachycardia or torsade de pointes and the QTC interval was 610 ms (normally under 450 in women). She received intravenous magnesium sulfate 2 g. Concurrent medications included enoxaparin, famotidine, magnesium hydroxide, ampicillin/sulbactam, nystatin suspension, midazolam, and 0.45% saline with 20 mmol/1 of potassium chloride. She had no further dysrhythmias after haloperidol was withdrawn. Eight days after the episode of torsade de pointes she had a QTC interval of 426 ms. 

In a double-blind study, 144 agitated patients who required emergency sedation were randomized to ziprasidone 20 mg (n = 46), droperidol 5 mg (n = 50), or midazolam 5 mg (n = 48) (13). Those who were sedated with droperidol or ziprasidone required rescue medications to achieve adequate sedation less often than those who were sedated with midazolam more remained agitated at 15 minutes after ziprasidone. There was akathisia in one patient who received droperidol, one who received midazolam (and subsequently droperidol rescue sedation), and four who received ziprasidone. There were no other adverse events. 

The usefulness and relative safety of midazolam in children have been reviewed (12). Myoclonic-like movements associated with midazolam in three full-term newborns were reversed by flumazenil (13). However, care must be taken when considering the use of flumazenil for reversal of midazolam-induced agitation, as no controlled trials have been published. 

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. 

Midazolam can cause paradoxical reactions, including increased agitation and poor cooperation (30,31). Often other drugs are required to continue the procedure successfully. Reversal of these reactions by flumazenil, a benzodiazepine antagonist, has been reported. 

Sevoflurane often causes postoperative delirium and agitation in children, and this may be severe. The effect of intravenous clonidine 2 pg/kg on the incidence and severity of postoperative agitation has been assessed in a double-blind, randomized, placebo-controlled trial in 40 boys who had anesthetic induction with sevoflurane after oral midazolam premedication (32). There was agitation in 16 of those who received placebo and two of those who received clonidine the agitation was severe in six of those given placebo and none of those given clonidine. 

The effect of a single bolus dose of midazolam before the end of sevoflurane anesthesia has been investigated in a double-blind, randomized, placebo-controlled trial in 40 children aged 2-7 years (33). Midazolam significantly reduced the incidence of delirium after anesthesia. However, when it was used for severe agitation, midazolam only reduced the severity of agitation without abolishing it. 

TREC Collaborative Group. Rapid tranquillisation for agitated patients in emergency psychiatric rooms a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003 327(7417) 708-13. 

Huf G, Coutinho ESF, Adams CE, Borges RVS, Ferreira MAV, Silva FJF, Pereira AJCR, Abreu FM, Lugao SM, Santos MPCP, Gewandsznajder M, Mercadante VRP, Lange W Jr, Dias CL Rapid tranquillisation for agitated patients in emergency psychiatric rooms a randomised trial of midazolam versus haloperidol plus promethazine. Br Med J 2003 327 708-11. 

Sherwin TS, Green SM, Khan A, Chapman DS, Dannenberg B. Does adjunctive midazolam reduce recovery agitation after ketamine sedation for pediatric procedures A randomized, double-bhnd, placebo-controlled trial. Ann Emerg Med 2000 35(3) 229-38. 

Treat agitation (see p 24) or severe anxiety states with diazepam or midazolam (p 415). Butyrophenones such as haloperidol (p 451) are useful despite a small theoretic risk of lowering the seizure threshold. 

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