Avoid common mistakes on your manuscript.
Dear Editor,
Refractory agitation (RA) is a frequent and challenging problem in patients in the pediatric intensive care unit (PICU). After exclusion of imminent hypoxia, the differential diagnosis of RA includes: (i) delirium due to the underlying critical illness, and/or (ii) withdrawal, and/or (iii) disinhibition/paradoxical arousal due to benzodiazepines [1, 2]. In most cases, haloperidol gives satisfactory results [3], although RA may persist despite this treatment. Also benzodiazepines are often given, but may be ineffective or even contraindicated to restore patient comfort. After all, many patients in a PICU already receive or have received benzodiazepines and may have developed a certain level of tolerance. In others, benzodiazepines should be avoided because of associated disinhibition, which has particularly been observed in critically and/or terminally ill children [2]. Therefore, a rescue strategy may be needed [1].
A possible solution for the treatment of RA is the addition of methotrimeprazine (MTZ, also known as levomepromazine or Nozinan), an aliphatic phenothiazine neuroleptic drug with a weak antipsychotic, but strong sedative effect. This classic neuroleptic is commonly used as co-medication in emergency psychiatry in adults to treat acute psychosis or mania by reducing levels of agitation, anger, and aggressiveness [4], thereby improving comfort for all—the patient, family, and members of the multidisciplinary team. There is no literature to allow for advisory dosages of MTZ in children with RA; however, in palliative care 0.1 mg/kg IV/SC/8 h is suggested [1]. In adults, maximum dosages of t.i.d. 25–50 mg/orally/24 h MTZ are common. Potential, but rare side effects of MTZ include tardive dyskinesia, akathisia, neuroleptic malignant syndrome, and extrapyramidal and cholinergically mediated side effects; a contraindication is bone marrow depression [4].
We recently used MTZ in four critically ill children presenting with RA (patient characteristics are summarized in Table 1). All patients initially received standard analgosedative treatment according to consensus guidelines [5]. Two patients developed delirium for which an individually titrated dosage of haloperidol remained insufficient or ineffective. A third patient suffered from therapy-resistant agitation during slowly weaning from sedation, for which several analgosedatives were unsatisfactorily given. The last patient experienced repeated periods of agitation due to progressive pulmonary hypertension, for which amongst others haloperidol seemed ineffective. In all cases, additional intravenous or enteral administered MTZ successfully reduced RA and restored the comfort of the child and everyone involved. No side effects were observed. Long-term outcome of our four patients varied: patients 3 and 4 were treated with MTZ in the terminal phase of palliative care and died peacefully, patient 2 did not experience further agitation after treatment, and patient 1 still receives MTZ successfully.
We conclude that once RA still continues after adequate 24-h dosages of D2-blocking agents, the addition of MTZ by trial and error titration might be a useful option [4]. We would like to reintroduce and underscore, on the basis of empirical evidence and by analogy to what is known in adults [1, 4], the use and effectiveness of MTZ in the treatment of RA in critically ill children in the PICU.
References
Goldman A, Hain R, Liben S (2006) Oxford textbook of palliative care for children. Oxford University Press, Oxford
Sadock BJ, Va S (2009) Kaplan and Sadock’s comprehensive textbook of psychiatry, 9th edn. Lippincott Williams and Wilkins, Philadelphia
Schieveld JN, Staal M, Voogd L, Fincken J, Vos G, van Os J (2010) Refractory agitation as a marker for pediatric delirium in very young infants at a pediatric intensive care unit. Intensive Care Med 36:1982–1983
Green B, Pettit T, Faith L, Seaton K (2004) Focus on levomepromazine. Curr Med Res Opin 20:1877–1881
Playfor S, Jenkins I, Boyles C, Choonara I, Davies G, Haywood T, Hinson G, Mayer A, Morton N, Ralph T, Wolf A, United Kingdom Paediatric Intensive Care Society Sedation, Analgesia and Neuromuscular Blockade Working Group (2006) Consensus guidelines on sedation and analgesia in critically ill children. Intensive Care Med 32:1125–1136
Acknowledgments
We gratefully acknowledge Dr. O. Bekers, MSc, PhD, clinical chemist and R.W.M.A van der Zanden, PharmD, hospital pharmacist for their expertise and help regarding our patients.
Open Access
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Author information
Authors and Affiliations
Corresponding author
Additional information
S. van der Zwaan and R. J. Blankespoor contributed equally to this paper.
Rights and permissions
Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License (https://creativecommons.org/licenses/by-nc/2.0), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
About this article
Cite this article
van der Zwaan, S., Blankespoor, R.J., Wolters, A.M.H. et al. Additional use of methotrimeprazine for treating refractory agitation in pediatric patients. Intensive Care Med 38, 175–176 (2012). https://doi.org/10.1007/s00134-011-2414-y
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-011-2414-y