David R Williamson

Université de Montréal | UdeM · Faculty of Pharmacy

Background Delirium, agitation, and anxiety may hinder weaning from mechanical ventilation and lead to increased morbidity and healthcare costs. The most appropriate clinical approach to weaning in these contexts remains unclear and challenging to clinicians. The objective of this systematic review was to identify effective and safe interventions t...

Objective The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI). Methods We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LI...

Background: Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological...

The World Health Organization (WHO) designates access to essential drugs as a critical concern due to persistent shortages and escalating costs. Drug shortages are a function of demand and supply mismatches that can be affected by manufacturing, distribution, as well as regulatory, economic, or political considerations. Prior to the 2019 coronaviru...

Background: Agitated behaviors are problematic in intensive care unit (ICU) patients recovering from traumatic brain injury (TBI) as they create substantial risks and challenges for healthcare providers. To date, there have been no studies evaluating their epidemiology and impact in the ICU. Prior to planning a multicenter study, assessment of recr...

Objective: Adults sustaining a traumatic brain injury (TBI) are at risk of sleep disturbances during their recovery, including when such an injury requires hospitalization. However, the sleep-wake profile, and internal and external factors that may interfere with sleep initiation/maintenance in hospitalized TBI patients are poorly understood. Thi...

Background and objective Psychotropic medications are frequently prescribed during acute care, even in older patients. They represent a risk for inappropriate long-term use and increase the overall risk of morbidity and mortality in this population. Our project aimed to evaluate the feasibility of a psychotropic medication stewardship program led...

Background: Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. Methods: The patients presented in this report took part i...

Background Opioids are often prescribed for acute pain to emergency department (ED) discharged patients, but there is a paucity of data on their short-term use. The purpose of this study was to synthesize the evidence regarding the efficacy of prescribed opioids compared to non-opioid analgesics for acute pain relief in ED-discharged patients. Met...

Purpose Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exist for antimicrobial dosing adjustments in patients requiring extracorporeal membrane oxygenation (ECMO) therapy, particularly in the pediatric population. A systematic review was conducted...

Background Agitation is a common clinical problem encountered in the intensive care unit (ICU). Treatment options are based on clinical experience and sparse quality literature. Aim The aim of this study was to evaluate the effect of valproic acid (VPA) as adjuvant treatment for agitation in the ICU as well as to identify independent predictors of...

Introduction Recent evidence has shown that vitamin C has some analgesic properties in addition to its antioxidant effect and can, therefore, reduce opioid use during recovery time. Vitamin C analgesic effect has been explored mostly during short-term postoperative context or in disease-specific chronic pain prevention, but never after acute muscul...

Guidelines for the determination of death by neurologic criteria (DNC) require an absence of confounding factors if clinical examination alone is to be used. Drugs that depress the central nervous system suppress neurologic responses and spontaneous breathing and must be excluded or reversed prior to proceeding. If these confounding factors cannot...

Objective To assess the efficacy of melatonin and melatonergic agonist for the treatment of delirium in hospitalized patients. Methods Embase, MEDLINE, PsycINFO, PubMed, CENTRAL, Cochrane Database of Systematic Reviews, TRIP Medical Database, ClinicalTrials.gov and Google were searched from inception to October 2022. Randomized controlled trials...

OBJECTIVES: The objective of this review was to depict the physiological and clinical rationale for the use of vasopressin in hemodynamic support of organ donors. After summarizing the physiological, pharmacological concepts and preclinical findings, regarding vasopressin’s pathophysiological impacts, we will present the available clinical data....

Background Although a majority of North Americans is in favor of organ donation, registration remains challenging. Community pharmacists are highly accessible frontline health care professionals that could contribute to a new common registration donation consent system. Aim The objective of the study was to assess self-perceived professional role a...

Background: Canadian data on intracranial hemorrhage (ICH) associated with oral anticoagulation is limited. Objectives: Primary study outcomes were baseline hematoma volumes and in-hospital mortality in patients with ICH associated with direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Second-ary outcomes included the use of f...

Background: In recent years, multiple population pharmacokinetic models have been developed for drugs such as tobramycin that need therapeutic drug monitoring. Some of these models have been used to develop a priori dosing regimens for their respective populations. However, these dosing regimens may not apply to other populations. Therefore, this...

Introduction: Clostridioides difficile infection (CDI) is a serious complication of critical illness. The objective of the study was to determine its incidence, prevalence, timing, severity, predictors, and outcomes. Methods: We performed a prospective nested cohort study of CDI within a randomized trial comparing Lactobacillus rhamnosus GG to p...

Background: ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use post-hospitalization. Research question: For sedative-naïve older adult ICU survivors, how common is receipt of new and persistent sedative prescript...

We conducted a pilot study in patients aged 75 years and older. Psychotropic medications were assessed for potential deprescription, and if eligible, a recommendation from the stewardship pharmacist was made to the medical team. Among 183 patients, 93.4 % were eligible for a potential deprescription. A total of 298 prescriptions were evaluated by t...

Purpose Current literature suggests a significant epidemiological association between traumatic brain injury (TBI) and proximal upper limb fractures in addition to major clinical consequences. A systematic review was conducted to assess how TBI is taken into consideration in interventional studies on shoulder fractures. Methods The following data...

Abstract Objectives Self-reported approaches that assess opioid usage can be subject to social desirability and recall biases that may underestimate actual pill consumption. Our objective was to determine the accuracy of patient self-reported opioid consumption using a 14-day daily paper or electronic diary. Design Prospective cohort study. Sett...

Background: An external evaluation is crucial before clinical applications; however, only a few gentamicin population pharmacokinetic (PopPK) models for critically ill patients included it in the model development. In this study, we aimed to evaluate gentamicin PopPK models developed for critically ill patients. Methods: The evaluated models wer...

Introduction: Despite availability of selection criteria, different interpretations can lead to variability in the appreciation of donor eligibility with possible viable organs missed. Our primary objective was to test the perception of feasibility of potential organ donors through the survey of a small sample of external evaluators. Methods: Clin...

Considering the aminoglycosides’ characteristics in terms of efficacy and toxicity, multiple dosing recommendations and nomograms have been suggested over several decades. The objective is to describe the dosing and monitoring practices of amikacin, gentamicin, and tobramycin in critically ill patients across health care institutions in the provinc...

Objective: The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients. Data sources A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms:...

IMPORTANCE Limiting opioid overprescribing in the emergency department (ED) may be associated with decreases in diversion and misuse. OBJECTIVE To review and analyze interventions designed to reduce the rate of opioid prescriptions or the quantity prescribed for pain in adults discharged from the ED. DATA SOURCES MEDLINE, Embase, CINAHL, PsycINFO,...

BACKGROUND: Analgesia monitoring is essential to preserve comfort in critically ill sedated patients with traumatic brain injury (TBI). Although pupil dilation (PD) and pain behaviors can be used to assess analgesia, these indicators require application of noxious stimulations for elicitation. Recently, the pupillary light reflex (PLR) has emerged...

Background Analgesia with fentanyl can be associated with hyperalgesia (higher sensitivity to pain) and can contribute to escalating opioid use. Our objective was to assess the relationship between emergency department (ED) acute pain management with fentanyl compared to other opioids, and the quantity of opioids consumed two-week after discharge....

Importance Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections...

Purpose To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation,...

Introduction Agitation and violent behaviours are common conditions developed by patients with acute traumatic brain injury (TBI) in intensive care units (ICUs). Healthcare professionals caring for these patients have various tools to manage these behaviours, but lack of a formal protocol to assess and manage them makes caring for these patients a...

Purpose Adequate dosing of antimicrobials is critical to properly treat infections and limit development of resistance and adverse effects. Limited guidance exists for antimicrobial dosing adjustments in patients requiring extracorporporeal membrane oxygenation (ECMO) therapy. A systematic review was conducted to delineate the pharmacokinetics (PK)...

Purpose The underassessment of pain is a major barrier to effective pain management, and the lack of pain assessment documentation has been associated with negative patient outcomes. This study aimed to 1) describe the contextual factors related to pain assessment and management in five Québec intensive care units (ICUs); 2) describe their pain ass...

Background: Although aminoglycosides are often used as treatment for Gram-negative infections, optimal dosing regimens remain unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycoside pharmacokinetics in this population. Objective: This review provides comprehensive data on the phar...

Background Although aminoglycosides are often used as treatment for Gram-Negative infections, optimal dosing regimens remains unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycosides’ pharmacokinetics in this population. Objective The review provides comprehensive data on the pharmac...

Background: Behavioural disturbances such as agitation are common following traumatic brain injury and can interfere with treatments, cause self-harm and delay rehabilitation. As there is a lack of evidence on the optimal approach to manage agitation in recovering TBI patients, various pharmacological agents are used including antipsychotics, anti...

Background Direct oral anticoagulants (DOAC) are hydrophilic drugs with plasma levels inversely proportional to lean body mass. Sarcopenic patients with low muscle mass may be at risk for supra‐therapeutic DOAC levels and bleeding complications. We therefore sought to examine the influence of lean body mass on DOAC levels in older adults with atria...

OBJECTIVE After craniectomy, although intracranial pressure (ICP) is controlled, episodes of brain hypoxia might still occur. Cerebral hypoxia is an indicator of poor outcome independently of ICP and cerebral perfusion pressure. No study has systematically evaluated the incidence and characteristics of brain hypoxia after craniectomy. The authors’...

Purpose: This case report describes a patient with dabigatran accumulation due to acute kidney injury on chronic kidney disease, requiring multiple administration of idarucizumab along with renal replacement therapy because of rebound effect causing numerous episodes of bleeding. Summary: An 86-year-old man on dabigatran etexilate 110 mg twice d...

Objective: The objectives of this study were to systematically identify and describe guidelines for the care of neurologically deceased donors and to evaluate their methodological quality, with the aim of informing and supporting the new Canadian guidelines for the management of organ donors. Methodology: Following a systematic search, we includ...

Purpose Montreal has been the epicentre of the coronavirus disease (COVID-19) pandemic in Canada. Given the regional disparities in incidence and mortality in the general population, we aimed to describe local characteristics, treatments, and outcomes of critically ill COVID-19 patients in Montreal. Methods A single-centre retrospective cohort of...

A sensitive and selective high-performance liquid chromatographic method coupled to tandem mass spectrometry was developed and validated for the quantification of morphine, hydromorphone, fentanyl, midazolam and propofol and their metabolites morphine-3-β-d-glucuronide, morphine-6-β-d-glucuronide, hydromorphone-3-β-d-glucuronide, 1′-hydroxymidazola...

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.PurposeTo examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adult...

During the coronavirus disease (COVID-19) global pandemic, urgent strategies to alleviate shortages are required. Evaluation of the feasibility, practicality, and value of drug conservation strategies and therapeutic alternatives requires a collaborative approach at the provincial level. The Ontario COVID-19 ICU Drug Task Force was directed to crea...

Introduction Agitated behaviours (AB) constitute hallmark behaviours of intensive care unit (ICU) patients recovering from traumatic brain injury (TBI). These behaviours create significant challenges for patients and healthcare providers including the need for pharmacologic treatment, delaying mechanical ventilation weaning and mobilization, and co...

Introduction: In critically ill patients with TBI, agitated behaviors may often be threatening for patients safety and for clinical teams. Antipsychotics are commonly used for the acute management of these agitated behaviors. However, animal TBI models suggest that repeated use of antipsychotic agents reduce cognitive and functional recovery. It re...

Background The Withdrawal Assessment Tool–1 (WAT-1) has been validated for assessing iatrogenic withdrawal syndrome in critically ill children receiving mechanical ventilation, but little is known about this syndrome in critically ill adults. Objective: To evaluate the validity and reliability of the WAT-1 in critically ill adults. Methods: A pro...

Purpose: Right ventricular RV dysfunction among transplant recipients correlates with transplant outcome, but its frequency in donors is unknown. The purpose of this study was to describe the epidemiology of RV dysfunction in potential heart donors." Methods: In a seven-year retrospective study of potential heart donors, we explored the incidenc...

Background Brain tissue oxygenation (PbtO2) in traumatic brain injury (TBI) is known to be dependent on cerebral blood flow (CBF) which remains difficult to assess during the very early phase of TBI management. This study evaluates if blood flow velocity measurement with 2D color-coded transcranial Doppler (TCD) can predict cerebral hypoxic episode...

Background: Although commonly prescribed, the efficacy of levothyroxine to improve heart function in neurologically deceased donors is unclear. We evaluated the feasibility of a randomized controlled trial to compare levothyroxine to placebo on the variation of left ventricular ejection fraction, in hemodynamically unstable donors. Methods: We c...

Purpose We sought to characterize Canadian physicians’ perspectives and stated practices regarding their hemodynamic care of deceased organ donors. Methods We designed a 24-item electronic survey that was independently pretested for relevance, clarity, and intra-rater reliability by ten critical care clinicians. With the help of provincial organ d...

Objective: Opioid side effects are common when treating chronic pain. However, the frequency of opioid side effects has rarely been examined in acute pain conditions, particularly in a post emergency department (ED) setting. The objective of this study was to evaluate the short-term incidence of opioid-induced side effects (constipation, nausea/vo...

Background: Antimicrobial misuse leading to drug resistance is a growing concern for clinicians. Improving antimicrobial stewardship programmes through development of new tools could be part of the solution. Aim: To evaluate antimicrobial use in hospitalized patients after implementation of an antimicrobial checklist for ward-based clinical phar...

Introduction : Opioid side effects are common when treating chronic pain. However, the rate of opioid side effects for acute pain has rarely been examined, particularly in the post emergency department (ED) setting. The objective of this study was to evaluate the short-term incidence of opioid induced side effects (constipation, nausea/vomiting, di...

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 evalua...

OBJECTIVE Avoiding decreases in brain tissue oxygenation (PbtO 2 ) after traumatic brain injury (TBI) is important. How best to adjust PbtO 2 remains unclear. The authors investigated the association between partial pressure of oxygen (PaO 2 ) and PbtO 2 to determine the minimal PaO 2 required to maintain PbtO 2 above the hypoxic threshold (> 20 mm...

RATIONALE: Spinal cord injuries greatly impact morbidity and mortality. High cervical injury level often leads to the need of definitive airway. Whether pneumonia is a modifiable risk factor for mechanical ventilation (MV) and prolonged MV in this population is unclear in the literature. OBJECTIVES: The objective of this study was to determine whet...

Background: Few studies have evaluated the quality of oral anticoagulant management by community pharmacists. There is no complete set of quality indicators available for this purpose. Objective: To develop a set of specific quality indicators to assess oral anticoagulant management by community pharmacists for patients with atrial fibrillation...

Background: The Ontario Senior Friendly Hospital Strategy recognizes delirium prevention and management as a top priority and recommends implementation of delirium screening as well as management protocols. This strategy proposes that hospitals monitor 2 specific indicators: (1) rate of baseline delirium screening and (2) rate of hospital-acquired...

Objective: To (1) provide an overview of the epidemiology, clinical presentation, and risk factors of iatrogenic opioid withdrawal in critically ill patients and (2) conduct a literature review of assessment and management of iatrogenic opioid withdrawal in critically ill patients. Data sources: We searched MEDLINE (1946-June 2017), EMBASE (1974...

Background: Opioids and benzodiazepines are frequently used in the intensive care unit (ICU). Regular use and prolonged exposure to opioids in ICU patients followed by abrupt tapering or cessation may lead to iatrogenic withdrawal syndrome (IWS). IWS is well described in pediatrics, but no prospective study has evaluated this syndrome in adult ICU...

Purpose: Investigate the relationship between psychoactive drugs and delirium. Materials and methods: Prospective observational study of 520 critically ill adult patients admitted ≥24h to 6 intensive care units (ICUs). Data were collected on psychoactive drug exposure, use of sedation administration strategies, and incident delirium (Intensive C...

Study objective: Because the pharmacokinetic evaluation of valproic acid (VPA) based on total drug concentration may be misleading in patients with hypoalbuminemia as a result of saturable protein binding and saturable metabolism, we sought to investigate the usefulness of therapeutic drug monitoring of unbound VPA concentration in a real-world cl...

Background Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia. Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown. Patients/Methods Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care un...

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of sedative, analgesic, and anaesthetic drugs on neurological outcomes in adults with moderate-to-severe TBI. © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Objective: Intensive care unit (ICU)-acquired delirium has been associated with increased morbidity and mortality. Prevention strategies including modification of delirium risk factors are emphasized by practice guidelines. No study has specifically evaluated modifiable delirium risk factors in trauma ICU patients. Our goal was to evaluate modifia...