Morphine versus hydromorphone in pediatrics: a narrative review of latest indications and optimal use in neonates and children.

The management of pain in pediatrics is multimodal and includes non-pharmacologic and pharmacologic approaches. Opioids, and particularly morphine and hydromorphone, are frequently used to treat moderate-to-severe pain. The goals of this review are to describe the pharmacological characteristics of both drugs, to cover the latest evidence of their respective indications, and to promote their safe use in pediatrics. Morphine is the most studied opioid in children and is known to be safe and effective. Morphine and hydromorphone can be used to manage acute pain and are usually avoided when treating chronic non-cancer pain. Current evidence suggests that both opioids have a similar efficacy and adverse effect profile. Hydromorphone has not been studied in neonates but in some centers, it has been used instead of morphine for certain patients. In palliative care, the use of opioids is often indicated and their benefits extend beyond analgesia; indications include treatment of central neuropathic pain in children with severe neurologic impairment and treatment of respiratory distress in the imminently dying patients. The longstanding belief that the use of well-titrated opioids hastens death should be abandoned as robust evidence has shown the opposite. With the current opioid crisis, a responsible use of opioids should be promoted, including limiting the opioid prescription to the patient's anticipated needs, optimizing a multimodal analgesic plan including the use of non-pharmacological measures and non-opioid medications, and providing information on safe storage and disposal to patients and families. More data is needed to better guide the use of morphine and hydromorphone in children.

Association of intraoperative dexmedetomidine use with postoperative hypotension in unilateral hip and knee arthroplasties: a historical cohort study.

PURPOSE: Dexmedetomidine is frequently used as a sedative agent for orthopedic surgery patients undergoing total hip or knee arthroplasty. Although the benefits of dexmedetomidine are well described in the literature, there is also potential for harm, especially regarding the hemodynamic effects of dexmedetomidine in the postoperative setting. METHODS: This historical cohort study included all primary unilateral total hip or knee arthroplasties conducted from April 2017 to February 2020 in a single, university-affiliated, tertiary care centre (Jewish General Hospital, Montreal, QC, Canada). We used multivariable logistic regression to analyze the predictors for postoperative hypotension, defined as a systolic blood pressure < 90 mm Hg or any systolic blood pressure while on a vasopressor infusion in the postanesthesia care unit. Models were validated using calibration and discrimination with bootstrapping technique. RESULTS: One thousand five hundred and eighty-eight patients were included in this study. Postoperative hypotension occurred in 413 (26%) patients. Statistically significant predictors for postoperative hypotension included female sex (adjusted odds ratio [aOR], 3.24; 95% confidence interval [CI], 2.29 to 4.58), a history of transient ischemic attack or cerebrovascular accident (aOR, 1.97; 95% CI, 1.04 to 3.72), and intraoperative dexmedetomidine use (aOR, 2.61; 95% CI, 1.99 to 3.42). Moreover, the risk of postoperative hypotension was approximately two times higher than baseline, with a total intraoperative dexmedetomidine dose above 50 µg (relative risk, 1.99; 95% CI, 1.63 to 2.44; P < 0.001). A higher preoperative systolic blood pressure (aOR, 0.98; 95% CI, 0.97 to 0.99) was a protective factor for postoperative hypotension. CONCLUSION: In this historical cohort study, dexmedetomidine was a strong risk factor for postoperative hypotension in total hip or knee arthroplasty patients. Dexmedetomidine, and particularly at high cumulative doses above 50 µg, should be administered judiciously in high-risk surgical patients to minimize the risk of postoperative hypotension.

RéSUMé: OBJECTIF: La dexmédétomidine est fréquemment utilisée comme agent sédatif pour les patients en chirurgie orthopédique bénéficiant d'une arthroplastie totale de la hanche ou du genou. Bien que les avantages de la dexmédétomidine soient bien décrits dans la littérature, il existe également un potentiel de préjudice, en particulier en ce qui touche aux effets hémodynamiques de la dexmédétomidine dans un contexte postopératoire. MéTHODE: Cette étude de cohorte historique comprenait toutes les arthroplasties totales unilatérales primaires de la hanche ou du genou réalisées entre avril 2017 et février 2020 dans un seul centre de soins tertiaires universitaire (Hôpital général juif, Montréal, QC, Canada). Nous avons utilisé la régression logistique multivariable pour analyser les prédicteurs d'hypotension postopératoire, définie comme une tension artérielle systolique < 90 mmHg ou toute tension artérielle systolique pendant une perfusion de vasopresseurs en salle de réveil. Les modèles ont été validés à l'aide de l'étalonnage et de la discrimination avec une technique d'auto-amorçage. RéSULTATS: Mille cinq cent quatre-vingt-huit patients ont été inclus dans cette étude. Une hypotension postopératoire est survenue chez 413 (26 %) patients. Les prédicteurs statistiquement significatifs d'une hypotension postopératoire comprenaient le sexe féminin (rapport de cotes ajusté [RCA], 3,24; intervalle de confiance [IC] à 95 %, 2,29 à 4,58), des antécédents d'accident ischémique transitoire ou d'accident vasculaire cérébral (RCA, 1,97; IC 95 %, 1,04 à 3,72) et l'utilisation peropératoire de dexmédétomidine (RCA, 2,61; IC 95 %, 1,99 à 3,42). De plus, le risque d'hypotension postopératoire était environ deux fois plus élevé que la valeur initiale, avec une dose peropératoire totale de dexmédétomidine supérieure à 50 µg (risque relatif, 1,99; IC 95 %, 1,63 à 2,44; P < 0,001). Une tension artérielle systolique préopératoire plus élevée (RCA, 0,98; IC 95 %, 0,97 à 0,99) était un facteur protecteur contre l'hypotension postopératoire. CONCLUSION: Dans cette étude de cohorte historique, la dexmédétomidine était un facteur de risque important d'hypotension postopératoire chez les patients bénéficiant d'une arthroplastie totale de la hanche ou du genou. La dexmédétomidine, et en particulier à des doses cumulatives élevées supérieures à 50 µg, devrait être administrée judicieusement chez les patients chirurgicaux à haut risque afin de minimiser le risque d'hypotension postopératoire.

Morphine or hydromorphone: which should be preferred? A systematic review.

OBJECTIVE: To systematically review available paediatric literature on comparisons between morphine (Mo) and hydromorphone (Hm), to guide clinicians to rationally use these medications. DESIGN: Systematic review within four databases for all studies published from 1963 to July 2019. SETTING: All paediatric settings. ELIGIBILITY: All studies comparing Mo to Hm in individuals younger than 21 years. MAIN OUTCOME MEASURES: The primary outcome was to compare clinical efficacy and side effects of Mo and Hm. The secondary outcomes were the comparison of pharmacokinetic profiles and the description of predefined Mo to Hm conversion ratios used across the paediatric literature. RESULTS: Among 754 abstracts reviewed, 59 full-text articles met inclusion criteria and 24 studies were included in the analysis: 4 studies compared pharmacodynamics of Mo and Hm and 20 studies reported the use of a predefined Mo to Hm conversion ratio. Most studies had a poor methodological quality. Available evidence suggests that, when given intravenously, the equianalgesic ratio of Mo to Hm is 5:1. Intravenous administration with this ratio results in a similar rate of adverse effects, including pruritus and nausea. The epidural administration with a ratio of 10:1 results in more pruritus and urinary retention with Mo than Hm. Pharmacokinetic data were reported in only one study. A wide range of pre-established ratios for different routes of administration were reported, but few were based on evidence. CONCLUSION: Current literature does not permit a rational choice between Mo and Hm. A ratio of 5:1 seems adequate for intravenous administration and leads to a similar rate of adverse effects.