Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled, emergency department trial

Wathen, Joe E.; Roback, Mark G.; MacKenzie, Todd A.; Bothner, Joan

doi:10.1067/mem.2000.111131

Cited by 248 publications

(127 citation statements)

References 33 publications

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“…The documented unpleasant side effects of ketamine, such as vivid dreams and emergence phenomena, are reported to be less common in paediatric patients and may be reduced by the concurrent use of benzodiazepines and opioids. 5 Although more recent evidence suggests no benefi t of adding benzodiazepines to the use of ketamine alone, 5 benzodiazepines have been added to reduce the potential for vivid dreams and to reduce the dose of ketamine.…”

Section: N B R I E Fmentioning

confidence: 99%

Intravenous conscious sedation in children for outpatient dentistry

Mikhael

Wray²,

Robb³

2007

Br Dent J

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Section: N B R I E Fmentioning

confidence: 99%

Intravenous conscious sedation in children for outpatient dentistry

Mikhael

Wray²,

Robb³

2007

Br Dent J

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“…6,10,27,28 In a systematic review of randomized trials of analgesia and sedation for reduction of fractures in children at a PEU, ketamine/ midazolam proved to be more effective as an analgesic and had fewer adverse effects than combinations of fentanyl/midazolam or propofol/midazolam. 1,2,4,5,15,25 When the level of satisfaction of parents and orthopedists were analyzed with analgesia for the orthopedic procedure, it was found that levels were quite high. Satisfaction was similar regardless of analgesic used, whether morphine or ketamine, a fact also described in other studies.…”

Section: Discussionmentioning

confidence: 99%

“…9,10 The sedation and analgesia schemes most commonly used in PEU involve the association of an opioid (morphine or fentanyl) with midazolam or the administration of ketamine with or without midazolam. [24][25][26] Morphine remains the most widely used drug in severe and chronic pain, however, fentanyl has been employed in more time-consuming procedures due to its faster start and peak of action and more prolonged effect. Ketamine is a dissociative agent, blocking opioid receptors, which rapidly induces sedation, profound analgesia, immobility and cataplegia, preserving spontaneous respiration.…”

Section: Discussionmentioning

confidence: 99%

Comparison of two analgesia protocols for the treatment of pediatric orthopedic emergencies

Barcelos

García

Portela

et al. 2015

Rev. Assoc. Med. Bras.

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Results: 13 patients were allocated to ketamine and 12 to morphine, without differences in relation to age, weight, gender, type of injury, and pain scale before the intervention. There was no failure in any of the groups, no differences in time to start the intervention and overall procedure time. The average hospital stay time was similar (ketamine = 10.8+5.1h versus morphine = 12.3+4.4hs; p=0.447). The median pain (faces pain scale) scores after the procedure was 2 in both groups. Amnesia was noted in 92.3% (ketamine) and 83.3% (morphine) (p=0.904). Parents said they were very satisfied in relation to the analgesic intervention (84.6% in the ketamine group and 66.6% in the morphine group; p=0.296). The satisfaction of the orthopedist regarding the intervention was 92.3% in the ketamine group and 75% in the morphine group (p=0.222). Conclusion: by producing results similar to morphine, ketamine can be considered as an excellent option in pain management and helps in the reduction of dislocations and closed fractures in pediatric emergency rooms.

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“…Interestingly, children patients receiving intravenous ketamine with midazolam for sedation show more pronounced adverse effects with patients younger than 10 years [Wathen et al, 2000]. Dosing infants and children is impeded by a general lack of knowledge about drug bioavailability and disposition in this specific population particularly when concomitant drugs are used as anesthetic mixtures.…”

Section: Evaluation Of the Effect Of Midazolam And Ketoconazole On Kementioning

confidence: 99%

“…A recent study demonstrated that combined ketamine-midazolam provided better results then midazolam alone for sedation of young children [Moreira et al, 2013]. But, children patients younger then 10 years receiving intravenous ketamine along with midazolam display more pronounced adverse effects [Wathen et al, 2000]. Drug-drug interactions have become an important issue in health care and concomitant drug administration is widely recognized to be a major cause.…”

Section: Evaluation Of the Effect Of Midazolam And Ketoconazole On Kementioning

confidence: 99%

In vitro ketamine CYP3A‐mediated metabolism study using mammalian liver S9 fractions, cDNA expressed enzymes and liquid chromatography tandem mass spectrometry

Santamaria

Pailleux

Beaudry

2014

Biomedical Chromatography

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Ketamine is widely used in medicine in combination with several benzodiazepines including midazolam. The objectives of this study were to develop a novel HPLC-MS/SRM method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well-known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 x 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 µL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05-50 µM. The precision (%CV) and accuracy (%NOM) observed were ranging from 3.9-7.8 and 95.9.2-111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentration and K m values of 18.4 µM, 13.8 µM and 30.8 µM for rat, dog and human liver S9 fractions were observed respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T 1/2 = 159.4 min) compared with rat (T 1/2 = 12.6 min) and dog (T 1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC 50 and K i values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed the formation of norketamine is mediated by CYP3A but results suggest an important contribution from others isoenzymes, most likely CYP2C particularly in rat.3

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Does midazolam alter the clinical effects of intravenous ketamine sedation in children? A double-blind, randomized, controlled, emergency department trial

Cited by 248 publications

References 33 publications

Intravenous conscious sedation in children for outpatient dentistry

Intravenous conscious sedation in children for outpatient dentistry

Comparison of two analgesia protocols for the treatment of pediatric orthopedic emergencies

In vitro ketamine CYP3A‐mediated metabolism study using mammalian liver S9 fractions, cDNA expressed enzymes and liquid chromatography tandem mass spectrometry

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