Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies.

WHAT IS KNOWN AND OBJECTIVE: Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: The literature search was conducted in PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane register of systematic reviews, DARE, CINAHL, Trip database, CMA infobase and NICE evidence from inception to February 2018. Grey literature was examined. We included studies reporting frequency, risk factors or symptomatology of iatrogenic withdrawal of opioids, benzodiazepines (or both) in critically ill patients. We considered all study designs except case reports and case series. We excluded studies on neonatal abstinence syndrome, alcohol withdrawal, studies on chronic opioid and/or benzodiazepine users and studies on prevention or treatment of withdrawal in critical care patients. Two independent reviewers applied the inclusion and exclusion criteria. Pairs of reviewers independently abstracted data and evaluated methodological quality using the Cochrane Collaboration Tool, Newcastle-Ottawa or QUADAS-2. Details regarding study design, outcomes, definition, evaluation and type of withdrawal (opioid, benzodiazepine or mixed) were collected. Cumulative doses and duration of opioids and benzodiazepines were collected. RESULTS AND DISCUSSION: We identified 21 866 unique citations and 153 full texts were assessed for eligibility. Thirty-four studies were included; the majority were observational and few included adults. In prospective studies, mixed withdrawal was observed in 7.5%-100% of patients in paediatric studies and ranged from 16.7% to 55% in adults. Symptomatology of withdrawal was not well described. Risk factors included higher cumulative dose and prolonged administration of opioids and benzodiazepines. WHAT IS NEW AND CONCLUSION: Iatrogenic withdrawal appears to be a frequent syndrome in critical care patients who received regular doses of opioids and/or benzodiazepines for ≥72 hours. Larger studies are required, especially in critically ill adults, to better define the syndrome and its symptomatology.

Pediatric Delirium: An Overlooked Diagnosis?

BACKGROUND: Delirium is well-recognized in adult inpatient care. However, it is often overlooked in children, being mistaken for pain, anxiety, or age-appropriate agitation. METHODS: To assess the impact of a formal teaching session on the diagnostic rates and management of pediatric delirium (PD) in a tertiary care center, we conducted a retrospective chart review of all hospitalized children diagnosed with PD between August 2003 and August 2018 at the CHU Sainte-Justine (Montreal, Canada). Diagnostic incidence and management were compared before (2003 to 2014) and after (2015 to 2018) a formal teaching session provided to pediatric residents, staff pediatricians, and intensive care physicians in December 2014. RESULTS: The two cohorts displayed similar demographics, PD symptomatology, PD duration (median: 2 days), and hospital stay duration (median: 11.0 and 10.5 days). However, we saw a major increase in diagnosis frequency after 2014 (from 1.84 to 7.09 cases/year). This increased diagnostic rate was most striking in the pediatric intensive care unit setting. Although symptomatic treatment with antipsychotics and alpha-2 agonists was similar between the two cohorts, patients diagnosed after 2014 were more often weaned from offending medications (benzodiazepines, anesthetics, and anticholinergics). All patients recovered fully. CONCLUSIONS: Formal teaching on the symptoms and management of PD was associated with an increase in diagnostic rate and an improved management of PD in our institution. Larger studies are required to assess standardized screening tools that may further enhance diagnostic rates and improve care for children with PD.

Integrated case management between primary care clinics and hospitals for people with complex needs who frequently use healthcare services in Canada: A multiple-case embedded study.

INTRODUCTION: Case management (CM) is recognized to improve care integration and outcomes of people with complex needs who frequently use healthcare services, but challenges remain regarding interaction between primary care clinics and hospitals. This study aimed to implement and evaluate an integrated CM program for this population where nurses in primary care clinics worked with a hospital case manager. METHODS: A multiple embedded case study was conducted in the Saguenay-Lac-Saint-Jean region (Québec, Canada), in four dyads including a clinic and a hospital. Mixed data collection included, at baseline and 6 months, interviews and focus groups with stakeholders, patient questionnaires (patient experience of integrated care and self-management), and emergency department (ED) visits in the previous 6 months. RESULTS: Integrated CM implementation was optimal when all stakeholders provided collective leadership, and were supportive of the program, particularly the physicians. The 6-month program enabled the observation of positive qualitative outcomes in most clinic-hospital dyads where implementation occurred. Full implementation was associated with improved care integration. DISCUSSION AND CONCLUSION: Integrated CM between primary care clinics and hospitals is a promising innovation to improve care integration for people with complex needs who frequently use healthcare services. Collective leadership and physicians' buy-in to integrated CM are important to foster the implementation.

The Impact of Implementing a "Pain, Agitation, and Delirium Bundle" in a Pediatric Intensive Care Unit: Improved Delirium Diagnosis.

Delirium is associated with significant negative outcomes, yet it remains underdiagnosed in children. We describe the impact of implementing a pain, agitation, and delirium (PAD) bundle on the rate of delirium detection in a pediatric intensive care unit (PICU). This represents a single-center, pre-/post-intervention retrospective and prospective cohort study. The study was conducted at a PICU in a quaternary university-affiliated pediatric hospital. All patients consecutively admitted to the PICU in October and November 2017 and 2018. Purpose of the study was describe the impact of the implementation of a PAD bundle. The rate of delirium detection and the utilization of sedative and analgesics in the pre- and post-implementation phases were measured. A total of 176 and 138 patients were admitted during the pre- and post-implementation phases, respectively. Of them, 7 (4%) and 44 (31.9%) were diagnosed with delirium ( p < 0.001). Delirium was diagnosed in the first 48 hours of PICU admission and lasted for a median of 2 days (interquartile range [IQR]: 2-4). Delirium diagnosis was higher in patients receiving invasive ventilation ( p < 0.001). Compliance with the PAD bundle scoring was 79% for the delirium scale. Score results were discussed during medical rounds for 68% of the patients in the post-implementation period. The number of patients who received opioids and benzodiazepines and the cumulative doses were not statistically different between the two cohorts. More patients received dexmedetomidine and the cumulative daily dose was higher in the post-implementation period ( p < 0.001). The implementation of a PAD bundle in a PICU was associated with an increased recognition of delirium diagnosis. Further studies are needed to evaluate the impact of this increased diagnostic rate on short- and long-term outcomes.

Suspected Overlap Between Serotonin Syndrome and Neuroleptic Malignant Syndrome in a Child Treated With Metoclopramide?

A 19-month-old child presented with fever and acute neurological deterioration with hypertonia, tremors, and clonus 1 day after starting metoclopramide. The clinical course of the patient was suggestive of neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS), which can both be triggered by metoclopramide. This first pediatric report of an overlap between NMS and SS associated to metoclopramide highlights the importance of considering this new entity and its consequences on treatment.

Strategies for the Prevention and Treatment of Iatrogenic Withdrawal from Opioids and Benzodiazepines in Critically Ill Neonates, Children and Adults: A Systematic Review of Clinical Studies.

BACKGROUND: Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines. PURPOSE: To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc. RESULTS: Thirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n = 4) or no differences (n = 6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20-35% and 32-66%, and treatment durations by 1.5-11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6-12 days (n = 4) for opioids and/or methadone and by 13 days (n = 1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias. CONCLUSION: Interventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions.

Opinion, experience and educational preferences concerning pharmacogenomics: an exploratory study of Quebec pharmacists.

Aim: To evaluate the current opinion, experience and educational preferences of pharmacists in Quebec concerning pharmacogenomics. Method: A web-based survey containing 25 questions was sent to all Quebec pharmacists. Results: Most pharmacists were willing to advise patients (81%) and physicians (84%) on treatment choices based on pharmacogenomic test results after proper training. Only 31% had been previously exposed to pharmacogenomic test results, and 91% were favorable to pharmacogenomics training, with e-learning through interactive video sessions (69%). The preferred training session length was between 1 and 3 h (59%). Hospital pharmacists were more often exposed to pharmacogenomic tests (p < 0.0001) and more frequently advised patients on treatment choices (p < 0.001) than community pharmacists. Conclusion: Pharmacists remain favorable toward pharmacogenomics, but its use in clinical practice stays limited. Identifying the educational preferences of pharmacists may help in the development of educational programs to help them integrate pharmacogenomics in their clinical practice.

Characteristics of self-management among patients with complex health needs: a thematic analysis review.

OBJECTIVE: There is a gap of knowledge among healthcare providers on characteristics of self-management among patients with chronic diseases and complex healthcare needs. Consequently, the objective of this paper was to identify characteristics of self-management among patients with chronic diseases and complex healthcare needs. DESIGN: Thematic analysis review of the literature. METHODS: We developed search strategies for the MEDLINE and CINAHL databases, covering the January 2000-October 2018 period. All articles in English or French addressing self-management among an adult clientele (18 years and older) with complex healthcare needs (multimorbidity, vulnerability, complexity and frequent use of health services) were included. Studies that addressed self-management of a single disease or that did not have any notion of complexity or vulnerability were excluded. A mixed thematic analysis, deductive and inductive, was performed by three evaluators as described by Mileset al. RESULTS: Twenty-one articles were included. Patients with complex healthcare needs present specific features related to self-management that can be exacerbated by deprived socioeconomic conditions. These patients must often prioritise care based on one dominant condition. They are at risk for depression, psychological distress and low self-efficacy, as well as for receiving contradictory information from healthcare providers. However, the knowledge and experiences acquired in the past in relation to their condition may help them improve their self-management skills. CONCLUSIONS: This review identifies challenges to self-management for patients with complex healthcare needs, which are exacerbated in contexts of socioeconomic insecurity and proposes strategies to help healthcare providers better adapt their self-management support interventions to meet the specific needs of this vulnerable clientele.

Effectiveness of risk communication interventions on the medical follow-up of youth treated with antidepressants.

Following reports of a potential association between antidepressants (ADs) and suicidal behaviour in youth, regulatory warnings were issued in May 2004, and clinical recommendations on medical follow-up were published in November 2007. Our study aimed at assessing the association between these communication interventions and medical follow-up of children (age 10-14) and adolescents (age 15-19) who initiate an AD treatment. A retrospective cohort study (1998-2008) was conducted among youth members of the Quebec public drug plan. Study outcomes consisted of adequate follow-up practice, defined as at least 1 medical visit per month during the first 3 months of treatment. The effect of each intervention on follow-up practices was determined through multivariate logistic regression analysis. The cohort included 4576 children and 12,419 adolescents. Two thirds of both children and adolescents had at least one medical visit during the first trimester of treatment, but only 20% had a frequency of at least one visit per month (i.e. adequate). The occurrence and frequency of visits did not change after either the warning nor the publication of the guidelines. Further interventions designed to optimize monitoring practices should be envisaged.

Pediatric drug-related problems: a multicenter study in four French-speaking countries.

BACKGROUND: Pediatric intensive care patients represent a population at high risk for drug-related problems. There are few studies that compare the activity of clinical pharmacists between countries. OBJECTIVE: To describe the drug-related problems identified and interventions by four pharmacists in a pediatric cardiac and intensive care unit. SETTING: Four pediatric centers in France, Quebec, Switzerland and Belgium. METHOD: This was a six-month multicenter, descriptive and prospective study conducted from August 1, 2009 to January 31, 2010. Drug-related problems and clinical interventions were compiled from four pediatric centers in France, Quebec, Switzerland and Belgium. Data on patients, drugs, intervention, documentation, approval and estimated impact were compiled. MAIN OUTCOME MEASURE: Number and type of drug-related problems encountered in a large pediatric inpatient population. RESULTS: A total of 996 interventions were recorded: 238 (24 %) in France, 278 (28 %) in Quebec, 351 (35 %) in Switzerland and 129 (13 %) in Belgium. These interventions targeted 270 patients (median 21 months old, 53 % male): 88 (33 %) in France, 56 (21 %) in Quebec, 57 (21 %) in Switzerland and 69 (26 %) in Belgium. The main drug-related problems were inappropriate administration technique (29 %), untreated indication (25 %) and supra-therapeutic dose (11 %). The pharmacists' interventions were mostly optimizing the mode of administration (22 %), dose adjustment (20 %) and therapeutic monitoring (16 %). The two major drug classes that led to interventions were anti-infectives for systemic use (23 %) and digestive system and metabolism drugs (22 %). Interventions mainly involved residents and all clinical staff (21 %). Among the 878 (88 %) proposed interventions requiring physician approval, 860 (98 %) were accepted. CONCLUSION: This descriptive study illustrates drug-related problems and the ability of clinical pharmacists to identify and resolve them in pediatric intensive care units in four French-speaking countries.

An evaluation of pharmacists' expectations towards pharmacogenomics.

BACKGROUND: Given their expertise in pharmacotherapy, pharmacists are well positioned to play a leading role in the implementation of pharmacogenomics in clinical practice. However, little is known about the opinions of pharmacists towards pharmacogenomics or their willingness to integrate this new field in their practice. METHODS: We conducted a survey of 284 pharmacists practicing in the province of Québec (Canada) to describe the opinions, expectations and concerns of pharmacists toward pharmacogenomics. RESULTS: Pharmacists were very hopeful regarding the potential role of pharmacogenomics. Moreover, more than 95% of responders would be willing to recommend pharmacogenomic testing. Nevertheless, only 7.7% of pharmacists currently felt comfortable advising patients based on pharmacogenomic test results. Accordingly, the majority of responders (96.6%) indicated that they would like to undertake continuing education related to pharmacogenomics. CONCLUSION: Pharmacists are extremely hopeful towards pharmacogenomic testing. Furthermore, a vast majority is willing to integrate these tests as part of their clinical practice. Proper education will be required if the integration of pharmacogenomics in patient care is to be optimal.