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Indian Pediatr 2011;48: 909 |
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Prolonged Sedation Related to
Erythromycin and Midazolam Interaction- A Word of Caution |
Subramanian Senthilkumaran and *Ponniah Thirumalaikolundu Subramanian,
Department of Accident, Emergency & Critical Care
Medicine,Sri Gokulam Hospital& Research Institute,
Salem 636 004; *Chennai Medical College and Research Center,
Irungalur, Trichy; Tamil Nadu, India.
Email:
[email protected]
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Procedural sedation in children is a challenging endeavor. We report an
interesting case of prolonged sedation probably due to an interaction
between erythromycin and midazolam in a child.
A 6 year old, 24 kg boy was referred for do an
outpatient magnetic resonance imaging of the pelvis and femur as he was
suffering with fever and progressive pain in hip area and limping. The boy
was otherwise healthy, with an unremarkable medical history and review of
systems. He was taking some medicines for fever, and the details were not
known. As he was having a fear of injection, oral midazolam suspension of
0.5 mg/kg was given and patient’s cooperation was achieved throughout the
procedure. His physiologic parameters remained well within age-adjusted
normal values. At the termination of the study after 45 minutes, he
remained deeply sedated with a Ramsay Sedation Score of 5 and was
transferred uneventfully to the emergency department for monitoring. 30
minutes after completion of the imaging study, he remained profoundly
asleep; hence intravenous flumazenil of 0.01 mg/kg bolus was given to
shorten post procedure recovery time. Although he was satisfactorily
aroused from sedation with a modified Aldrete score of 9, he was admitted
to the intensive care unit for overnight continuous cardio-respiratory
monitoring. The mother brought the remaining tablets which were
erythromycin and paracetamol. A possibility of prolonged midazolam effect
due to erythromycin was entertained. He remained hemo-dynamically and
neurologically stable in the ICU through-out the night and discharged home
without any sequelae.
Midazolam is the most commonly used drug in pediatric
procedural sedation, as it can be delivered by all routes of
administration. It has a rapid onset and a short elimination half-life
(1.17 h) compared with other benzodiazepines, and thus makes it
particularly suitable for brief procedures [2]. Unfortunately, injections
are one of the most frightening, distressing and sometimes painful aspect,
and hence, oral route is preferred. Both erythromycin and midazolam are
substrates of the cytochrome P450 3A4 enzyme system and compete for enzyme
sites. Metabolism of midazolam is inhibited resulting in decrease in
midazolam clearance, and an increase in the half-life and serum
concentration of midazolam. The degree of inhibition of 3A4 enzyme varies
among the macrolides. The reported frequency of interaction in descending
order is erythromycin, clarithromycin, roxithromycin and azithromycin [3].
Olkkola, et al. [4] had demonstrated that sedation produced by
single dose of midazolam was prolonged in patients receiving erythromycin.
Hiller, et al. [5] had
reported loss of consciousness following intravenous erythromycin
administration due to interaction with oral midazolam administered.
As macrolides are prescribed in medical practice and
these patients are likely to be seen by different practitioners for
procedures requiring sedation, it is worth while to elicit clinical
history and verify the drugs given before administering midazolam. This
report illustrates the importance of avoiding midazolam for patients
receiving erythromycin.
References
1. Godwin SA, Caro DA, Wolf SJ, Jagoda AS, Charles R,
Marett BE, et al. Clinical policy for procedural sedation and
analgesia in the emergency department. American College of Emergency
Physicians. Ann Emerg Med. 2005;45:177-96.
2. Nordt SP, Clark RF. Midazolam: a review of
therapeutic uses and toxicity. J Emerg Med. 1997;15:357-65.
3. Ito K, Ogihara K, Kanamitsu S, Itoh T. Prediction of
the in vivo interaction between midazolam and macrolides based on
in vitro studies using human liver microsomes. Drug Metab Dispos.
2003;31:945-54.
4. Olkkola KT, Aranko K, Luurila H, Hiller A,
Saarnivaara L, Himberg JJ, et al. A potentially hazardous
interaction between erythromycin and midazolam. Clin Pharmacol Ther.
1993;53:298-305.
5. Hiller A, Olkkola KT, Isohanni P, Saarnivaara L.
Unconsciousness associated with midazolam and erythromycin. Br J Anaesth.
1990;65:826-8.
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