Effects of a Midazolam-Ketamine Admixture in Human Volunteers: DISCUSSION

In: Health

19 Sep 2009


The encouraging combination of these 2 relatively short-acting agents with similar pharmacokinetics and complimentary pharmacological properties, which lacks ketamine’s adverse reactions, has been clearly substantiated.

Midazolam is the benzodiazepine of choice when combined with ketamine in terms of physiological homeostasis and recovery time.

Both drugs are water soluble, can be mixed together without precipitation, and remain stable with a similar pH. Ketamine-midazolam infusion solutions have been shown to be chemically compatible up to at least 97 hours. As was seen in this study, midazolam has been shown to decrease ketamine-associated dysphoria as the result of its amnestic and dream-altering properties. We did not observe any dysphoria, unpleasant dreaming, or emergence-type reactions. Midazolam was administered first to achieve anxiolysis and sedation, and then the ketamine was administered. When ketamine is to be used as an adjunct to midazolam sedation, it is always administered after the midazolam has taken effect and not vice versa as postprocedural agitation will not beeliminated. Unless necessary, it is not advisable to reverse the effects of the midazolam as the undesirable effects of the ketamine could become present. generic cialis soft tabs

Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that can cause dysfunction of cor-ticolimbic neurons by inhibiting excitatory pathways and causing the signs and symptoms of schizophrenia. The coadministration of midazolam with gamma amniobu-tyric acid receptor agonist properties is successful in inhibiting and preventing these phenomena.

The hypnotic effects of midazolam together with ketamine have been demonstrated to be additive; hence when used in combination a lower dose of each agent is required. As biotransformation of ketamine takes place primarily in the liver, the combined use of benzodiazepines that also require hepatic metabolism will prolong recovery time. The proportion of ketamine to midazolam can be varied according to individual needs, but for sedation and analgesia to supplement local anesthesia, ketamine in doses higher than those used are likely to produce more side effects with little additional benefits.

Cardiorespiratory parameters have not been previously studied with such a sedoanalgesic admixture. Of importance is the fact that unlike most other sedative techniques, with this technique cardiorespiratory parameters remained stable and did not decrease.
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Bailie et al have shown that a midazolam-ketamine combination was comparable with a technique using propofol and alfentanil. The use of ketamine allows for the avoidance of opioids and their associated side effects. When ketamine replaces narcotic analgesics, sedation has been noted to be superior and is associated with a more rapid onset and recovery with significantly fewer side effects such as hypoxia, hypotension, and reduced respiratory rate. Although not seen in our study, transient oxygen desaturation has been known to occur with ketamine-assisted midazolam sedation.

Ketamine is known to produce sympathomimetic effects via both central and peripheral mechanisms. The increases in plasma catecholamines are caused by central sympathetic stimulation and not due to respiratory effects. Ketamine inhibits the re-uptake of catecholamines at the adrenergic nerve terminal with the resultant sympathomimetic effects, but this phenomenon was not seen as the coadministered midazolam appeared to diminish this effect. Your life is worth living. Buy viagra soft tabs online

The transient rise in heart rate and systolic blood pressure coincided with the transient increase in the plasma catecholamines epinephrine and norepinephrine that followed the initial loading bolus dose.

The effects on circulating plasma catecholamines of any midazolam-ketamine admixture have not been studied to date. It has, however been previously shown that when ketamine is infused as the sole agent, it transiently increases plasma epinephrine and norepinephrine as well, but a coadministered infusion of midazolam at sedative doses or inhalational anesthesia oblates these increases. Bolus doses are known to increase plasma epinephrine and norepinephrine significantly more than microdrip administrations. Plasma dopamine levels are usually not affected by ketamine administration. It may be wise to initially avoid the use of exogenous catecholamines for 15 minutes after the initial ketamine boluses. female pink viagra

Few studies have addressed the ease and convenience of simultaneously administering the agents midazolam and ketamine. With this sedoanalgesic technique, spontaneous breathing is maintained and intubation together with muscle relaxants are not required while cardiorespiratory parameters remain close to baseline levels. This combined technique is simple, reliable, safe, and inexpensive, and in selected cases may be considered as an alternative to traditional conscious sedation or general anesthesia. Further study of this admixture is warranted.

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