Methotrimeprazine for the management of End-Of-Life Symptoms in Infants and Children

Abstract

Objective: This retrospective chart review assessed the efficacy, dose, and safety of methotrimeprazine in palliating end-of-life symptoms in children and infants. Methods: A retrospective chart review was conducted of 18 hospitalized pediatric patients who were treated with methotrimeprazine in their last two weeks of life. Data collected included age, diagnosis, symptoms, methotrimeprazine dose, route, efficacy, and any documented adverse effects. Results: Patients’ ages ranged from 16 days to 17 years. Underlying conditions included malignancies, trauma, and various neurodegenerative and congenital diseases. All patients (n=18) were treated for symptoms of agitation, delirium, or restlessness. Most patients also experienced respiratory secretions/congestion (n=15), pain (n=13), and/ or dyspnea (n=9). Less common symptoms included nausea/emesis (n=5) and spasticity (n=1). Methotrimeprazine dosages ranged from 0.02 mg/kg/dose to 0.5 mg/kg/dose. Routes of administration included intravenous (n=13), oral/gastrostomy tube (n=6), or subcutaneous (n=4). Sedation (n=6) was the only documented adverse effect, although when agitation was present, this was potentially an intended and perceived-to-be-beneficial effect. Conclusion: Methotrimeprazine, an old drug with diverse receptor activity and multiple routes of administration, appears to be an effective tool in treating complicated end-of-life symptoms in children and infants. This study provides a foundation for analysis with prospective and comparative trials, which may further quantify its benefit.

Management of Delirium in Palliative Care: a Review

“…Methotrimeprazine has also been used in palliative care, with a recent study carried out in infants and children experiencing symptoms of agitation, delirium, or restlessness, showing that different dosages of the drug (0.02-0.5 mg/kg/dose) and different routes (intravenous, oral/gastrostomy tube, or subcutaneous) appeared to be effective and safe [48]. Atypical or second-generation APs are a class of drugs with a 5HT2A-D2 antagonism that conventional APs do not have, although the receptor-binding profiles of the atypical APs vary consistently between the single drugs [49].…”

The effect of levomepromazine on the healthy and injured developing mouse brain – An in vitro and in vivo study

“…A pharmacologic class with the potential to counter these noxious effects are phenothiazines which have been shown to be anti-excitotoxic, anti-apoptotic and anti-oxidative ( Geng et al, 2017 ; An et al, 2017 ; Varga et al, 2017 ; Gonzalez-Munoz et al, 2010 ). The long-standing phenothiazine LMP is currently experiencing a revival due to its favourable risk profile, flexible routes of administration, convenient dosing interval, as well as its potent sedative, analgesic and anaesthetic mechanisms of action ( van der Zwaan et al, 2012 ; Hohl et al, 2013 ). These properties render it particularly attractive for use in NICUs.…”

“…The experiment used 5-day-old (P5) healthy, uninjured mouse pups, comparable to a gestational age of 24–32 weeks in human terms and coinciding with a particularly vulnerable phase of the developing brain ( Clowry et al, 2014 ). LMP dosages were chosen according to pediatric standards ( van der Zwaan et al, 2012 ; Hohl et al, 2013 ). As a somatometric endpoint, body weight development following LMP administration was monitored.…”

“…Levomepromazine (LMP), also known as methotrimeprazine, is a phenothiazine neuroleptic drug with strong analgesic and sedative effects, which is commonly used in palliative and end-of-life care ( Dietz et al, 2013 ). It is also used off-label as an add-on sedative in Pediatric Intensive Care Units, as it appears to have no major side effects ( van der Zwaan et al, 2012 ; Hohl et al, 2013 ; Snoek et al, 2014 ). With regard to brain injury, various phenothiazines proved to be neuroprotective due to their anti-excitotoxic, anti-apoptotic and anti-oxidative properties ( Geng et al, 2017 ; An et al, 2017 ; Varga et al, 2017 ; Gonzalez-Munoz et al, 2010 ).…”

Effective pain management strategies for common pediatric conditions

“…37 Neuroleptics like methotrimeprazine can alleviate pain associated with anxiety, restlessness, or nausea. 38 Benzodiazepines are primarily used to manage anxiety and muscle spasms but have limited analgesic properties. 39 Multimodal analgesia approaches are recommended, including non-opioid medications like acetaminophen, NSAIDs, antispasmodics, gabapentinoids, and intravenous ketamine.…”