World Library  
Flag as Inappropriate
Email this Article


Systematic (IUPAC) name
Clinical data
Trade names Dormicum, Hypnovel, Versed
  • AU: C
  • US: D (Evidence of risk)
Legal status
Routes of
Oral, IM, IV, parenteral
Pharmacokinetic data
Bioavailability Oral ~36%
I.M. 90%+
Protein binding 97%
Metabolism Liver 3A3, 3A4, 3A5
Onset of action within 5 min (IV), 15 min (IM), 20 min (oral)[1]
Biological half-life 1.8-6.4 hours
Duration of action 1 to 6 hrs[1]
Excretion Kidney
CAS Registry Number  Y
ATC code N05
PubChem CID:
DrugBank  Y
ChemSpider  Y
Chemical data
Formula C18H13ClFN3
Molecular mass 325.78

Midazolam, marketed under the trade names Versed among others, is a medication used for anesthesia, procedural sedation, trouble sleeping, and severe agitation.[1] It works by making people sleepy, decreasing anxiety, and causing a loss of ability to create new memories.[1] It is also useful for the treatment of seizures.[2] Midazolam can be give by mouth, intravenously, by injection into a muscle, sprayed into the nose, or in the cheek.[1][2] When given intravenously it begins working typically within five minutes, when injected into a muscle it can take fifteen minutes to begin working.[1] Effects last for between one and six hours.[1] Side effects can include a decrease in efforts to breathe, low blood pressure, and sleepiness.[1] Tolerance to its effects and withdrawal syndrome may occur following long term use.[3] Paradoxical effects, such as increased activity, can occur especially in children and older people.[3] There is evidence of risk when used during pregnancy but no evidence of harm with a single dose during breastfeeding.[4][5] It is of the benzodiazepine class and works through the GABA neurotransmitter.[1] Midazolam first came into use in 1976.[6] It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[7] Midazolam is available as a generic medication and is not very expensive.[4] Wholesale a vial is about 0.35 USD.[8] In many countries it is a controlled substance.[1]


  • Medical uses 1
    • Seizures 1.1
    • Procedural sedation 1.2
    • Problems sleeping 1.3
    • Agitation 1.4
    • End of life care 1.5
  • Contraindications 2
  • Side effects 3
    • Pregnancy and breastfeeding 3.1
    • Elderly 3.2
    • Tolerance, dependence, and withdrawal 3.3
    • Overdose 3.4
    • Detection in body fluids 3.5
    • Interactions 3.6
  • Pharmacokinetics 4
  • History 5
  • Society and culture 6
    • Cost 6.1
    • Availability 6.2
    • Legal status 6.3
    • Marketing authorization 6.4
    • Use in executions 6.5
  • References 7
  • External links 8

Medical uses


Midazolam is sometimes used for the acute management of seizures. Long-term use for the management of epilepsy is not recommended, however, due to the significant risk of tolerance (which renders midazolam and other benzodiazepines ineffective) and the significant side effect of sedation.[9] A benefit of midazolam is that in children it can be administered buccally or intranasally at home or at school for emergency control of acute seizures, including status epilepticus.[10][11] Midazolam is effective for status epilepticus that has not improved following other treatments, and has advantages of being water-soluble, having a rapid onset of action and not causing metabolic acidosis from the propylene glycol vehicle, which occurs with other benzodiazepines. Drawbacks include a high degree of breakthrough seizures—due to the short half-life of midazolam—in over 50% of people treated, as well as treatment failure in 14–18% of people with refractory status epilepticus. Tolerance develops rapidly to the anticonvulsant effect, and the dose may need to be increased by several times to maintain anticonvulsant therapeutic effects. With prolonged use, tolerance and tachyphylaxis can occur and the elimination half-life may increase, up to days.[3][12]There is evidence buccal and intranasal midazolam is easier to administer and more effective than rectally administered diazepam in the emergency control of seizures.[13][14][15]

Procedural sedation

Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for preoperative sedation, for the induction of general anesthesia, and for sedation of people who are ventilated in critical care units.[16][17] Midazolam is superior to diazepam in impairing memory of endoscopy procedures, but propofol has a quicker recovery time and a better memory-impairing effect.[18] It is the most popular benzodiazepine in the intensive care unit (ICU) because of its short elimination half-life, combined with its water solubility and its suitability for continuous infusion. However, for long-term sedation, lorazepam is preferred due to its long duration of action,[19] and propofol has advantages over midazolam when used in the ICU for sedation, such as shorter weaning time and earlier tracheal extubation.[20]

Midazolam is sometimes used in neonatal intensive care units. When used, additional caution is required in newborns; midazolam should not be used for longer than 72 hours due to risks of tachyphylaxis, and the possibility of development of a benzodiazepine withdrawal syndrome, as well as neurological complications. Bolus injections should be avoided due to the increased risk of cardiovascular depression, as well as neurological complications.[21] Midazolam is also sometimes used in newborns who are receiving mechanical ventilation, although morphine is preferred, owing to its better safety profile for this indication.[22]

Problems sleeping

Oral midazolam is indicated for the short-term treatment of moderately severe insomnia in people who have not reacted adequately to other hypnotics, and who have persistent trouble in falling asleep. Because of midazolam's extremely short duration, it is not used for people who have trouble staying asleep through the night; moderate- to long-acting benzodiazepines, such as temazepam, nitrazepam, flunitrazepam, and lormetazepam, are used for those purposes. Midazolam and other benzodiazepines may cause a deterioration in sleep quality.


Midazolam in combination with an antipsychotic drug is indicated for the acute management of schizophrenia when it is associated with aggressive or out-of-control behaviour.[23]

End of life care

In the final stages of end-of-life care, midazolam is routinely used at low doses via subcutaneous injection to help with agitation, myoclonus, restlessness or anxiety in the last hours or days of life.[24] At higher doses during the last weeks of life, midazolam is considered a first line agent in palliative continuous deep sedation therapy when it is necessary to alleviate intolerable suffering not responsive to other treatments,[25] but the need for this is rare.[26]


Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, in alcohol- or other drug-dependent individuals or those with comorbid psychiatric disorders.[27] Additional caution is required in critically ill patients, as accumulation of midazolam and its active metabolites may occur.[28] Kidney or liver impairments may slow down the elimination of midazolam leading to prolonged and enhanced effects.[29][30] Contraindications include hypersensitivity, acute narrow-angle glaucoma, shock, hypotension or head injury. Most are relative contraindications.

Side effects

Two 10-ml bottles labeled Midazolam  - the bottle on the left has a label in red and says 1 mg/ml; the one on the right is in green and says 5 mg/ml. Both bottles have much fine print.
Injectable midazolam in 1 and 5 mg/ml strengths

Side effects of midazolam in the elderly are listed above.[3] People experiencing amnesia as a side effect of midazolam are generally unaware their memory is impaired, unless they had previously known it as a side effect.[31]

Long-term use of benzodiazepines has been associated with long-lasting deficits of memory, and show only partial recovery six months after stopping benzodiazepines.[3] It is unclear whether full recovery occurs after longer periods of abstinence. Benzodiazepines can cause or worsen depression.[3] Paradoxical excitement occasionally occurs with benzodiazepines, including a worsening of seizures. Children and elderly individuals or those with a history of alcohol abuse and individuals with a history of aggressive behavior or anger are at increased risk of paradoxical effects.[3] Paradoxical reactions are particularly associated with intravenous administration.[32] After nighttime administration of midazolam, residual 'hangover' effects, such as sleepiness and impaired psychomotor and cognitive functions, may persist into the next day. This may impair the ability of users to drive safely and may increase the risk of falls and hip fractures.[33] Sedation, respiratory depression and hypotension due to a reduction in systematic vascular resistance, and an increase in heart rate can occur.[29][11] If intravenous midazolam is given too quickly, hypotension may occur. A “midazolam infusion syndrome” may result from high doses, and is characterised by delayed arousal hours to days after discontinuation of midazolam, and may lead to an increase in the length of ventilatory support needed.[34]

In susceptible individuals, midazolam has been known to cause a paradoxical reaction, a well-documented complication with benzodiazepines. When this occurs, the individual may experience anxiety, involuntary movements, aggressive or violent behavior, uncontrollable crying or verbalization, and other similar effects. This seems to be related to the altered state of consciousness or disinhibition produced by the drug. Paradoxical behavior is often not recalled by the patient due to the amnesia-producing properties of the drug. In extreme situations, flumazenil can be administered to inhibit or reverse the effects of midazolam. Antipsychotic medications, such as haloperidol, have also been used for this purpose.[35]

Midazolam is known to cause respiratory depression. In healthy humans, 0.15 mg/kg of midazolam may cause respiratory depression, which is postulated to be a central nervous system (CNS) effect.[36] When midazolam is administered in combination with fentanyl, the incidence of hypoxemia or apnea becomes more likely.[37]

Although the incidence of respiratory depression/arrest is low (0.1-0.5%) when midazolam is administered alone at normal doses,[38][39] the concomitant use with CNS acting drugs, mainly analgesic opiates, may increase the possibility of hypotension, respiratory depression, respiratory arrest, and death, even at therapeutics doses.[37][38][40][41] Potential drug interactions involving at least one CNS depressant were observed for 84% of midazolam users who were subsequently required to receive the benzodiazepine antagonist flumazenil.[42] Therefore, efforts directed toward monitoring drug interactions and preventing injuries from midazolam administration are expected to have a substantial impact on the safe use of this drug.[42]

Pregnancy and breastfeeding

Midazolam, when taken during the third trimester of pregnancy, may cause risk to the neonate, including benzodiazepine withdrawal syndrome, with possible symptoms including hypotonia, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Symptoms of hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.[43] Other neonatal withdrawal symptoms include hyperexcitability, tremor, and gastrointestinal upset (diarrhea or vomiting). Breastfeeding by mothers using midazolam is not recommended.[44]


Additional caution is required in the elderly, as they are more sensitive to the pharmacological effects of benzodiazepines, metabolise them more slowly, and are more prone to adverse effects, including drowsiness, amnesia (especially anterograde amnesia), ataxia, hangover effects, confusion, and falls.[3]

Tolerance, dependence, and withdrawal

A benzodiazepine dependence occurs in about one-third of individuals who are treated with benzodiazepines for longer than 4 weeks,[3] which typically results in tolerance and benzodiazepine withdrawal syndrome when the dose is reduced too rapidly. Midazolam infusions may induce tolerance and a withdrawal syndrome in a matter of days. The risk factors for dependence include dependent personality, use of a benzodiazepine which is short-acting, high potency and long-term use of benzodiazepines. Withdrawal symptoms from midazolam can range from insomnia and anxiety to seizures and psychosis. Withdrawal symptoms can sometimes resemble a persons underlying condition. Gradual reduction of midazolam after regular use can minimise withdrawal and rebound effects. Tolerance and the resultant withdrawal syndrome may be due to receptor down-regulation and GABAA receptor alterations in gene expression which results in long-term changes in the function of the GABAergic neuronal system.[3][45][46]

Chronic users of benzodiazepine medication who are given midazolam experience reduced therapeutic effects of midazolam, due to tolerance to benzodiazepines.[34][47] Prolonged infusions with midazolam results in the development of tolerance; if midazolam is given for a few days or more a withdrawal syndrome can occur. Therefore, in order to prevent a withdrawal syndrome a prolonged infusion needs to be gradually withdrawn and sometimes if necessary continued tapering of dose with an oral long-acting benzodiazepine such as clorazepate dipotassium. When signs of tolerance to midazolam occur during intensive care unit sedation the addition of an opioid or propofol is recommended. Withdrawal symptoms can include irritability, abnormal reflexes, tremors, clonus, hypertonicity, delirium and seizures, nausea, vomiting, diarrhea, tachycardia, hypertension, and tachypnea.[34]


A midazolam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. Benzodiazepine overdose in healthy individuals is rarely life-threatening with proper medical support; however, the toxicity of benzodiazepines increases when they are combined with other CNS depressants such as alcohol, opioids, or tricyclic antidepressants. The toxicity of benzodiazepine overdose and risk of death is also increased in the elderly and those with obstructive pulmonary disease or when used intravenously. Treatment is supportive; activated charcoal can be used within an hour of the overdose. The antidote for an overdose of midazolam (or any other benzodiazepine) is flumazenil.[29] While effective in reversing the effects of benzodiazepines it is not used in most cases as it may trigger seizures in mixed overdoses and benzodiazepine dependent individuals.[48][49]

Symptoms of midazolam overdose can include:[48][49]

Detection in body fluids

The concentrations of midazolam and/or its major metabolite, 1-hydroxymidazolam glucuronide, may be quantified in plasma, serum or whole blood in order to monitor for safety in those receiving the drug therapeutically, to confirm a diagnosis of poisoning in hospitalized patients or to assist in a forensic investigation of a case of fatal overdosage. Patients with renal dysfunction may exhibit prolongation of elimination half-life for both the parent drug and its active metabolite, with accumulation of these two substances in the bloodstream and the appearance of adverse depressant effects.[50]


Protease inhibitors, nefazodone, sertraline, grapefruit, fluoxetine, erythromycin, diltiazem, clarithromycin inhibit the metabolism of midazolam, leading to a prolonged action. St John's wort, rifapentine, rifampin, rifabutin, phenytoin enhance the metabolism of midazolam leading to a reduced action. Sedating antidepressants, antiepileptic drugs such as phenobarbital, phenytoin and carbamazepine, sedative antihistamines, opioids, antipsychotics and alcohol enhance the sedative effects of midazolam.[3] Midazolam is metabolized almost completely by cytochrome P450-3A4. Atorvastatin administration along with midazolam results in a reduced elimination rate of midazolam.[51] St John's wort decreases the blood levels of midazolam.[52] Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations.[53]


Midazolam is a short-acting benzodiazepine in adults with an elimination half-life of one to four hours; however, in the elderly, as well as young children and adolescents, the elimination half-life is longer.[54][32] Midazolam is metabolised into an active metabolite alpha1-hydroxymidazolam. Age-related deficits, renal and liver status affect the pharmacokinetic factors of midazolam as well as its active metabolite.[55] However, the active metabolite of midazolam is minor and contributes to only 10 percent of biological activity of midazolam. Midazolam is poorly absorbed orally, with only 50 percent of the drug reaching the bloodstream.[3] Midazolam is metabolised by cytochrome P450 (CYP) enzymes and by glucuronide conjugation. The therapeutic as well as adverse effects of midazolam are due to its effects on the GABAA receptors; midazolam does not activate GABAA receptors directly but, as with other benzodiazepines, it enhances the effect of the neurotransmitter GABA on the GABAA receptors (↑ frequency of Cl− channel opening) resulting in neural inhibition. Almost all of the properties can be explained by the actions of benzodiazepines on GABAA receptors. This results in the following pharmacological properties being produced: sedation, hypnotic, anxiolytic, anterograde amnesia, muscle relaxation and anti-convulsant.[29]


Midazolam is among about 35 benzodiazepines which are currently used medically,[56] and was synthesised in 1975 by Walser and Fryer at Hoffmann-LaRoche, Inc in the United States.[57] Owing to its water solubility, it was found to be less likely to cause thrombophlebitis than similar drugs.[58][59] The anticonvulsant properties of midazolam were studied in the late 1970s, but not until the 1990s did it emerge as an effective treatment for convulsive status epilepticus.[60] As of 2010, it is the most commonly used benzodiazepine in anesthetic medicine.[61] In acute medicine, midazolam has become more popular than other benzodiazepines, such as lorazepam and diazepam, because it is shorter lasting, is more potent, and causes less pain at the injection site.[56] Midazolam is also becoming increasingly popular in veterinary medicine due to its water solubility.[62]

Society and culture


Midazolam is available as a generic medication and is not very expensive.[4] Wholesale a vial is about 0.35 USD.[8]


Midazolam is available in the United States as a syrup or as an injectable solution.[63] Outside of the United States, midazolam is available in tablet form for oral administration.

Dormicum brand midazolam is marketed by Roche as white, oval, 7.5-mg tablets in boxes of two or three blister strips of 10 tablets, and as blue, oval, 15-mg tablets in boxes of two (Dormonid 3x) blister strips of 10 tablets. The tablets are imprinted with "Roche" on one side and the dose of the tablet on the other side. Dormicum is also available as 1-, 3-, and 10-ml ampoules at a concentration of 5 mg/ml. Another manufacturer, Novell Pharmaceutical Laboratories, makes it available as Miloz in 3- and 5-ml ampoules. Midazolam is the only water-soluble benzodiazepine available. Another maker is Roxanne Laboratories; the product in an oral solution, Midazolam HCl Syrup, 2 mg/ml clear, in a red to purplish-red syrup, cherry in flavor. It becomes soluble when the injectable solution is buffered to a pH of 2.9–3.7. Midazolam is also available in liquid form.[3] It can be administered intramuscularly,[11] intravenously,[64] intrathecally,[65] intranasally,[14] buccally,[66] or orally.[3]

Legal status

In the Netherlands, midazolam is a List II drug of the Opium Law. Midazolam is a Schedule IV drug under the Convention on Psychotropic Substances.[67] In the United Kingdom, midazolam is a Class C controlled drug.[68] In the United States, midazolam (DEA number 2884) is on the Schedule IV list of the Controlled Substances Act as a non-narcotic agent with low potential for abuse.[69]

Marketing authorization

In 2011, the European Medicines Agency granted a marketing authorisation for a buccal application form of midazolam, sold under the trade name Buccolam. Buccolam was approved for the treatment of prolonged, acute, convulsive seizures in people from three months to less than 18 years of age. This was the first application of a paediatric-use marketing authorisation.[70][71]

Use in executions

Oklahoma State Penitentiary, the site of the state of Oklahoma's execution chamber

The drug has been introduced for use in executions by lethal injection in certain jurisdictions in United States in combination with other drugs. It was introduced to replace pentobarbital after the latter's manufacturer disallowed that drug's use.

Midazolam has been used as part of a three-drug cocktail, with vecuronium bromide and potassium chloride in Florida and Oklahoma prisons.[72] Midazolam has also been used along with hydromorphone in a two-drug protocol in Ohio and Arizona.[72] Ohio used midazolam to execute Dennis McGuire in January 2014.[73]

Midazolam acts as a sedative to render the condemned prisoner unconscious, at which time the vecuronium bromide and potassium chloride are administered, stopping the prisoner's breathing and heart, respectively. Florida used midazolam to execute William Happ in October 2013.[74] The usage of midazolam in executions has become controversial after condemned inmate Clayton Lockett apparently regained consciousness and started speaking midway through his execution when the state of Oklahoma attempted to execute him with an untested three-drug lethal injection cocktail using 100 mg of midazolam. Prison officials reportedly discussed taking him to a hospital before he was pronounced dead of a heart attack 40 minutes after the execution began. An observing doctor stated that Lockett's vein had ruptured. It is not clear which drug or drugs caused his death or what quantities of vecuronium bromide and potassium chloride were released before the execution was cancelled.[75][76]

In Glossip v. Gross, three Oklahoma inmates argued that midazolam could not achieve the level of unconsciousness required for surgery, meaning severe pain and suffering was likely. They argued that midazolam was cruel and unusual punishment and thus contrary to the Eighth Amendment to the United States Constitution. In June 2015, the U.S. Supreme Court ruled they failed to prove that midazolam was cruel and unusual when compared to known alternatives.[77]


  1. ^ a b c d e f g h i j "Midazolam Hydrochloride". The American Society of Health-System Pharmacists. Retrieved Aug 1, 2015. 
  2. ^ a b Brigo, F; Nardone, R; Tezzon, F; Trinka, E (August 2015). "Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: A systematic review with meta-analysis.". Epilepsy & behavior : E&B 49: 325–36.  
  3. ^ a b c d e f g h i j k l m n Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (Aug 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics.". Acta Neurol Scand 118 (2): 69–86.  
  4. ^ a b c Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 21.  
  5. ^ "Midazolam use while Breastfeeding". Retrieved 29 August 2015. 
  6. ^ Agasti, TK (2011). Textbook of anaesthesia for postgraduates (First edition. ed.). p. 351.  
  7. ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  8. ^ a b "Midazolam". International Drug Price Indicator Guide. Retrieved 29 August 2015. 
  9. ^ Isojärvi, JI; Tokola RA. (December 1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability". J Intellect Disabil Res. 42 (1): 80–92.  
  10. ^ Appleton, R.; Macleod, S.; Martland, T.; Appleton, Richard (July 16, 2008). Appleton, Richard, ed. "Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children" (PDF). Cochrane Database of Systematic Reviews (3): CD001905.  
  11. ^ a b c Walker, M. (Sep 2005). "Status epilepticus: an evidence based guide". BMJ 331 (7518): 673–7.  
  12. ^ Murthy, JM. (Dec 2006). "Refractory status epilepticus". Neurol India 54 (4): 354–8.  
  13. ^ Eriksson, K.; Kälviäinen, R. (Nov 2005). "Pharmacologic management of convulsive status epilepticus in childhood.". Expert Rev Neurother 5 (6): 777–83.  
  14. ^ a b Wolfe, TR.; Macfarlane, TC. (May 2006). "Intranasal midazolam therapy for pediatric status epilepticus.". Am J Emerg Med 24 (3): 343–6.  
  15. ^ Sofou, K.; Kristjánsdóttir, R.; Papachatzakis, NE.; Ahmadzadeh, A.; Uvebrant, P. (Aug 2009). "Management of prolonged seizures and status epilepticus in childhood: a systematic review.". J Child Neurol 24 (8): 918–26.  
  16. ^ Brown, TB.; Lovato, LM.; Parker, D. (Jan 2005). "Procedural sedation in the acute care setting.". Am Fam Physician 71 (1): 85–90.  
  17. ^ O'Connor, M.; Bucknall, T.; Manias, E. (2009-09-21). "Sedation Management in Australian and New Zealand Intensive Care Units: Doctors' and Nurses' Practices and Opinions.". Am J Crit Care 19 (3): 285–95.  
  18. ^ McQuaid, KR.; Laine, L. (May 2008). "A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures.". Gastrointest Endosc 67 (6): 910–23.  
  19. ^ Arcangeli, A.; Antonelli, M.; Mignani, V.; Sandroni, C. (Nov 2005). "Sedation in PACU: the role of benzodiazepines.". Curr Drug Targets 6 (7): 745–8.  
  20. ^ De Cosmo, G.; Congedo, E.; Clemente, A.; Aceto, P. (Nov 2005). "Sedation in PACU: the role of propofol.". Curr Drug Targets 6 (7): 741–4.  
  21. ^ Rawicz, M. (Oct–Dec 2008). "[Recommendations for analgesia and sedation in neonatal intensive care]". Med Wieku Rozwoj 12 (4 Pt 1): 958–67.  
  22. ^ Bellù, R.; de Waal, KA.; Zanini, R.; Bellù, Roberto (2008). Bellù, Roberto, ed. "Opioids for neonates receiving mechanical ventilation". Cochrane Database of Systematic Reviews (1): CD004212.  
  23. ^ Huf, G.; Alexander, J.; Allen, MH.; Raveendran, NS.; Huf, Gisele (2009). Huf, Gisele, ed. "Haloperidol plus promethazine for psychosis-induced aggression" (PDF). Cochrane Database of Systematic Reviews (3): CD005146.  
  24. ^ Liverpool Care Pathway (January 2005). "Care of the Dying Pathway (lcp) (Hospital)" (PDF). United Kingdom. 
  25. ^ de Graeff, A.; Dean, M. (Feb 2007). "Palliative sedation therapy in the last weeks of life: a literature review and recommendations for standards.". J Palliat Med 10 (1): 67–85.  
  26. ^   "[I]n their last 24 hours... 31% had low doses of medication to [control distress from agitation or restlessness]... the remaining 4% required higher doses"
  27. ^ Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM.; Eschalier, A. (Nov 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Ann Pharm Fr 67 (6): 408–13.  
  28. ^ Cox, CE.; Reed, SD.; Govert, JA.; Rodgers, JE.; Campbell-Bright, S.; Kress, JP.; Carson, SS. (Mar 2008). "An Economic Evaluation of Propofol and Lorazepam for Critically Ill Patients Undergoing Mechanical Ventilation". Crit Care Med 36 (3): 706–14.  
  29. ^ a b c d Olkkola, KT.; Ahonen, J. (2008). "Midazolam and other benzodiazepines". Handb Exp Pharmacol. Handbook of Experimental Pharmacology 182 (182): 335–60.  
  30. ^ Verbeeck, RK. (Dec 2008). "Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction" (PDF). Eur J Clin Pharmacol 64 (12): 1147–61.  
  31. ^ Merritt P, Hirshman E, Hsu J, Berrigan M (2005). "Metamemory without the memory: are people aware of midazolam-induced amnesia?". Psychopharmacology (Berl) 177 (3): 336–43.  
  32. ^ a b Rosenbaum, A.; Kain, ZN.; Larsson, P.; Lönnqvist, PA.; Wolf, AR. (Sep 2009). "The place of premedication in pediatric practice" (PDF). Paediatr Anaesth 19 (9): 817–28.  
  33. ^ Vermeeren A. (2004). "Residual effects of hypnotics: epidemiology and clinical implications". CNS Drugs. 18 (5): 297–328.  
  34. ^ a b c Mencía, SB.; López-Herce, JC.; Freddi, N. (May 2007). "Analgesia and sedation in children: practical approach for the most frequent situations". J Pediatr (Rio J) 83 (2 Suppl): S71–82.  
  35. ^ Carissa E. Mancuso, Maria G. Tanzi, Michael Gabay (2004). "Paradoxical Reactions to Benzodiazepines: Midazolam". Pharmacotherapy.  
  36. ^ Reves JG, Fragen RJ, Vinik HR, Greenblatt DJ (1985). "Midazolam: Pharmacology and Uses". Anesthesiology 62 (3): 310–24.  
  37. ^ a b Bailey PL, Pace NL, Ashburn MA, Moll JW, East KA, Stanley TH; Pace; Ashburn; Moll; East; Stanley (1990). "Frequent hypoxemia and apnea after sedation with midazolam and fentanyl". Anesthesiology 73 (5): 826–30.  
  38. ^ a b Classen DC, Pestotnik SL, Evans RS, Burke JP (1992). "Intensive surveillance of midazolam use in hospitalized patients and the occurrence of cardiorespiratory arrest". Pharmacotherapy 12 (3): 213–16.  
  39. ^ Wright SW, Chudnofsky CR, Dronen SC, Wright MB, Borron SW; Chudnofsky; Dronen; Wright; Borron (1990). "Midazolam use in the emergency department". Am J Emerg Med 8 (2): 97–100.  
  40. ^ Yaster M, Nichols DG, Deshpande JK, Wetzel RC (1990). "Midazolam-fentanyl intravenous sedation in children: case report of respiratory arrest". Pediatrics 86 (3): 463–67.  
  41. ^ West JM, Estrada S, Heerdt M (1987). "Sudden hypotension associated with midazolam and sufentanil". Anesth Analg 66 (7): 693–94.  
  42. ^ a b Kawano DF, Ueta J, Sankarankutty AK, Pereira LR, de Freitas O; Ueta; Sankarankutty; Pereira; De Freitas (2009). "Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital". J Patient Saf 5 (2): 69–74.  
  43. ^ McElhatton PR. (Nov–Dec 1994). "The effects of benzodiazepine use during pregnancy and lactation". Reprod Toxicol. 8 (6): 461–75.  
  44. ^ Serreau, R.; Collége national des gynécologues et obstétriciens; Société française de médecine périnatale; Société française de néonatalogie; Société française de anesthésie et de réanimation (Apr 2010). "[Drugs during preeclampsia. Fetal risks and pharmacology]". Ann Fr Anesth Reanim 29 (4): e37–46.  
  45. ^ Fukuda K, Shoda T, Mima H, Uga H (August 2002). "Midazolam induces expression of c-Fos and EGR-1 by a non-GABAergic mechanism". Anesth. Analg. 95 (2): 373–8, table of contents.  
  46. ^ Cho HH, O'Connell JP, Cooney MF, Inchiosa MA (2007). "Minimizing tolerance and withdrawal to prolonged pediatric sedation: case report and review of the literature". J Intensive Care Med 22 (3): 173–9.  
  47. ^ Potokar J, Coupland N, Wilson S, Rich A, Nutt D (September 1999). "Assessment of GABA(A)benzodiazepine receptor (GBzR) sensitivity in patients on benzodiazepines". Psychopharmacology (Berl.) 146 (2): 180–4.  
  48. ^ a b A. Boon, Nicholas; Davidson, Stanley; R. Colledge, Nicki; Walker, Brian; Hunter, John G. (2006). Davidson's principles practice of medicine. Edinburgh: Elsevier/Churchill Livingstone. pp. 212–213.  
  49. ^ a b A Rastegar, Darius; I Fingerhood, Michael (2005). Addiction medicine: an evidence-based handbook. Philadelphia, PA: Lippincott Williams Wilkins. p. 80.  
  50. ^ Baselt, Randall C (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City CA: Biomedical Publications. pp. 1037–40.  
  51. ^ Mc Donnell, CG; Harte, S; O'driscoll, J; O'loughlin, C; Van Pelt, FN; Shorten, GD (2003). "The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam". Anaesthesia 58 (9): 899–904.  
  52. ^ Hu, Z.; Yang, X.; Ho, PC.; Chan, SY.; Heng, PW.; Chan, E.; Duan, W.; Koh, HL.; Zhou, S. (2005). "Herb-drug interactions: a literature review". Drugs 65 (9): 1239–82.  
  53. ^ Arayne, MS.; Sultana, N.; Bibi, Z. (Oct 2005). "Grape fruit juice-drug interactions". Pak J Pharm Sci 18 (4): 45–57.  
  54. ^ Barash, Paul G.; Cullen, Bruce F.; Stoelting, Robert K.; Cahalan, Michael D. (1 April 2009). Clinical Anesthesia (6 ed.). Lippincott Williams Wilkins. p. 588.  
  55. ^ Spina, SP.; Ensom, MH. (Mar 2007). "Clinical pharmacokinetic monitoring of midazolam in critically ill patients". Pharmacotherapy 27 (3): 389–98.  
  56. ^ a b Udaykumar, Padmaja (30 May 2008). Short Textbook of Pharmacology for Dental and Allied Health Sciences. Jaypee Brothers Medical Publishers. p. 128.  
  57. ^ Armin Walser, Rodney I. Fryer, Louis Benjamin. Imidazo[1,5-.alpha.][1,4]benzodiazepines. US Patent 4166185, issued to Hoffmann-LaRoche Aug 28, 1979.
  58. ^ Kaplan, Joel H.; Reich, David L.; Lake, Carol L.; Konstadt, Steven N. (15 May 2006). Cardiac Anesthesia (5 ed.). W.B. Saunders Company.  
  59. ^ Malamed, Stanley F. (16 October 2002). Sedation: a guide to patient management. St. Louis: Mosby. p. 335.  
  60. ^ S. Wheeler, Derek; R. Wong, Hector; P. Shanley, Thomas (2007). Pediatric critical care medicine: basic science and clinical evidence. London: Springer. p. 984.  
  61. ^ Oparil, Suzanne; Weber, Michael (22 April 2005). Hypertension: a companion to Brenner and Rector's the kidney (2 ed.). Philadelphia: Elsevier Mosby. p. 816.  
  62. ^ Riviere, Jim; Papich, Mark G. (30 Mar 2009). Veterinary Pharmacology and Therapeutics. Wiley-Blackwell. p. 358.  
  63. ^ FDA, ed. (2015). "Orange Book: Approved Drug Products; Midazolam". Retrieved 25 July 2015. 
  64. ^ Steib, A.; Hausberger, D.; Robillart, A.; Roche, A.; Franckhauser, D.; Dupeyron, JP. (Jun 2006). "[Anaesthetic considerations for interventional radiology]". Ann Fr Anesth Reanim 25 (6): 615–25.  
  65. ^ Ho, KM.; Ismail, H. (May 2008). "Use of intrathecal midazolam to improve perioperative analgesia: a meta-analysis". Anaesth Intensive Care 36 (3): 365–73.  
  66. ^ Beran, RG. (Apr 2008). "An alternative perspective on the management of status epilepticus". Epilepsy Behav 12 (3): 349–53.  
  67. ^  
  68. ^ Blackpool NHS Primary Care Trust (2007). "Medicines Management Update" (PDF). United Kingdom:  
  69. ^ "US DEA Schedules". 
  70. ^ "Monthly Report" (PDF).  
  71. ^ PR Newswire (6 September 2011). "ViroPharma's Buccolam (Midazolam, Oromucosal Solution) Granted European Marketing Authorization for Treatment of Acute Seizures". 
  72. ^ a b "State by State Lethal Injection". Death Penalty Information Center. Retrieved 2015-04-10. 
  73. ^ Ford D, Fantz A (2014-01-16). "Controversial execution in Ohio uses new drug combination". CNN. 
  74. ^ Watkins M (2013-10-15). "Happ executed using new drug". The Gainesville Sun. 
  75. ^ Ekholm E (2014-04-29). "One Execution Botched, Oklahoma Delays the Next -". The New York Times. 
  76. ^ "Oklahoma execution: Clayton Lockett writhes on gurney in botched procedure". The Guardian. 
  77. ^ "US Supreme Court backs use of contentious execution drug".  

External links

  • PubPK - Midazolam Pharmacokinetics
  • Rx-List - Midazolam (Versed)
  • Inchem - Midazolam
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.