Midazolam Pharmacodynamics and Pharmacokinetics during Acute Hypovolemia

Adams, Peter X.; Gelman, Simon; Reves, J. G.; Greenblatt, David J.; Alvis, J. M.; Bradley, Edwin L.

doi:10.1097/00000542-198508000-00004

Cited by 80 publications

(18 citation statements)

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“…disease status, comedication, obesity, liver function) it is also possible that as-yet unknown confounding factors [e.g. hypovolaemia (Adams et al 1985), septic shock (Shelly et al 1987) or ethnic differences (Kalow 1982)] might be responsible for the above phenomenon. It appears less likely that these surgery-related factors may have obscured a polymorphism in the metabolic data.…”

Section: Discussionmentioning

confidence: 99%

No Evidence of a Genetic Polymorphism in the Oxidative Metabolism of Midazolam

Kassai

Toth

Eichelbaum

et al. 1988

Clinical Pharmacokinetics

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The benzodiazepine midazolam is rapidly eliminated by oxidative metabolism. In young healthy volunteers elimination half-life (t1/2) is about 2.4 hours. A recent study showed a prolonged t1/2 from 8 to 22 hours in 6.5% of surgical patients, and a genetic polymorphism of midazolam's metabolism has been suggested. Therefore, we measured in 168 surgical patients the elimination of midazolam and its major hydroxylated metabolite (alpha-OH-midazolam) in blood and urine. Co-medication, disease status, smoking habits and alcohol intake were recorded; normal liver and kidney functions were assessed by routine laboratory tests. Midazolam was administered intravenously (0.1 to 0.2 mg/kg) for the induction of anaesthesia. Blood was drawn 1.5, 3, 4.5 and 6 hours after application and urine was collected for 6 hours. Plasma protein binding of midazolam was determined by equilibrium dialysis. Midazolam and alpha-OH-midazolam were measured in plasma by specific gas-liquid chromatography and in urine by high performance liquid chromatography. Data for the dose-corrected area under plasma-level curve of midazolam (AUC-midazolam/dose: 1.23 +/- 961 x 10(5) h/ml; mean +/- SD) and for the metabolic plasma ratio (AUC of alpha-OH-midazolam/AUC-midazolam: 0.52 +/- 0.28) demonstrated a log-normal distribution. Likewise, the percentage of the unbound fraction of midazolam in plasma (5.0 +/- 2.4%), urinary excretion of alpha-OH-midazolam (55.9 +/- 22.7% of dose) and the values for t1/2 (2.9 +/- 1.1 hours) did indicate a unimodal distribution. Age, comedication and smoking habits did not affect the disposition of midazolam. However, patients with regular intake of alcohol had a higher (p less than 0.05) metabolic ratio. Only in 3 patients could a prolonged t1/2 of midazolam from 7.5 to 10.2 hours be detected, but plasma levels and urinary excretion of alpha-OH-midazolam in those individuals were found to be normal. Therefore it is very unlikely that the oxidative metabolism of midazolam exhibits a genetic polymorphism.

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Section: Discussionmentioning

confidence: 99%

No Evidence of a Genetic Polymorphism in the Oxidative Metabolism of Midazolam

Kassai

Toth

Eichelbaum

et al. 1988

Clinical Pharmacokinetics

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“…Ventriküler yetmezliği olan hastalar, volatil anesteziklerin depresan etkilerine oldukça duyarlıdır. Bu ajanların hipovoleminin hipotansif etkilerini daha da potansiyalize ettiği bilinmektedir (15). Ayrıca, bu ajanlar; arteriyal barorefleks fonksiyonunu bozarlar.…”

Section: Discussionunclassified

Our Anaesthetic Experiences in Patients Undergoing Percutaneous Mitraclip Implantation

Erkılıç¹,

Kesimci²,

Döğer³

et al. 2016

Turk J Anaesth Reanim

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“…The literature has postulated that agitation may be associated with disinhibition effects caused by benzodiazepines, leading to behavior alterations like ataxia, sound hypersensibility, intense salivation, and muscular weakness (GARDOS, 1980;ADAMS et al, 1985;COURT;GREENBLATT, 2000). In a study by Robinson and Borer-Weir (2015) 2.5% of the animals presented slight myoclonia after administration of 2 mg kg -1 propofol followed by a bolus dose of 0.3 mg kg -1 midazolam or diazepam (ROBINSON; BORER-WEIR, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effects of combined midazolam and propofol in anesthesia induction and recovery of cats undergoing ovariohisterectomy

et al. 2015

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The objective of this study was to determine the effects of propofol and midazolam on induction of anesthesia in cats undergoing ovariohysterectomy, measured in terms of the quality of tracheal intubation, anesthesia induction, cardiorespiratory effects, and recuperation period. Thirty healthy adult cats were pretreated with acepromazine and morphine. After 30 min, they were divided into three groups: PG (n = 10), in which induction was performed with only intravenous propofol at doses required for intubation; MPG (n = 8), in which animals received intravenous midazolam (0.3 mg kg -1 ) administered over 30 s, followed by administration of propofol as in PG; and PMG (n = 9), in which propofol was first administered at a rate of 4 mg kg -1 min -1 , after which midazolam was administered (0.3 mg/kg), followed by re-administration of propofol. In order to perform a blinded study, the PG and PMG received a 0.9% NaCl solution volume similar to the midazolam dose before induction (0.06 mL/kg). Similar to the other groups, the PG and MPG received (0.06 mL kg -1 ) saline 30 s after administration of propofol. In order to mimic the administration of midazolam, the saline solution was administered for 30s. The PG received 11.0 ± 1.38 mg kg -1 propofol, a greater dose than that administered to the PMG (p < 0.001) and MPG (p < 0.01), which received 7.9 ± 1.92 and 9.1 ± 2.20 mg kg -1 , respectively. There were no differences in the intubation scores between groups. Previous use of midazolam did not affect agitation or excitement in cats; both sequences of propofol-midazolam administration are feasible, but the propofol-midazolam sequence was superior due to the lower propofol dose. Key words: Benzodiazepines, castration, dogs, feline ResumoO objetivo deste estudo foi determinar os efeitos de propofol e midazolam na indução da anestesia em gatas submetidas a ovariossalpingohisterectomia quanto a qualidade da intubação orotraqueal e da indução da anestesia, efeitos cardiorrespiratórios e períodos de recuperação. Foram utilizadas 27 gatas adultas e hígidas que foram pré-tratadas com acepromazina e morfina. Decorridos 30 minutos, foram distribuídas em três grupos: no GP (n=10), a indução foi realizada somente com propofol por via intravenosa na dose necessária para intubação orotraqueal; no GMP (n=8), os animais receberam midazolam (0,3 mg/kg) administrado pela via intravenosa em 30s, e em seguida o propofol foi administrado segundo os critérios do grupo propofol; no GPM (n=9), administrou-se, inicialmente, propofol na velocidade de 4 mg/kg/min; posteriormente, administrou-se midazolam (0,3 mg/kg), e o restante da indução foi realizado com propofol. Para que o estudo fosse cego, os animais dos grupos GP e GPM receberam solução salina no volume similar à dose de midazolam antes da indução (0,06 ml/kg). Da mesma forma, os grupos GP e GMP receberam solução de NaCl a 0,9% (0,06 ml/kg) após 30s de administração de propofol. Com objetivo de mimetizar a administração do midazolam, a solução salina foi administrada em 30s. O GP r...

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Midazolam Pharmacodynamics and Pharmacokinetics during Acute Hypovolemia

Cited by 80 publications

References 0 publications

No Evidence of a Genetic Polymorphism in the Oxidative Metabolism of Midazolam

No Evidence of a Genetic Polymorphism in the Oxidative Metabolism of Midazolam

Our Anaesthetic Experiences in Patients Undergoing Percutaneous Mitraclip Implantation

Effects of combined midazolam and propofol in anesthesia induction and recovery of cats undergoing ovariohisterectomy

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