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...

Background Delirium is a common and serious syndrome of acute brain dysfunction associated with negative outcomes. Melatonin may have a role in delirium prevention for critically ill adults based on data from non-critically ill patient populations. Our objective was to assess the feasibility of a multi-centre, randomized, placebo-controlled trial t...

We hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and...

Introduction Recent evidence has shown that vitamin C has analgesic and opioid sparing properties in immediate postoperative context. However, this has never been studied for acute musculoskeletal (MSK) emergency department (ED) injuries. The aim of this pilot study is to evaluate the feasibility of conducting a randomized placebo-controlled study...

Background Previous systematic reviews on fracture and fall prevention have generally shown no efficacy with calcium or vitamin D alone and conflicting findings with that of vitamin D combined with calcium. Despite these findings, increases in vitamin D and calcium prescriptions have been reported in many countries, as many clinicians, guidelines a...

Background: Few studies have evaluated opioid consumption after various inpatient surgical procedures. Objectives: To describe opioid prescription patterns and to characterize patient-reported use of opioids after surgery. Methods: This single-centre prospective observational study was conducted between February and October 2021 at the Jewish Gener...

Importance: Hospital admission for a critical illness episode creates communication breakpoints and can lead to medication discrepancies during hospital stays. Due to the patient’s underlying condition and the care setting, chronic medications such as cardiovascular medication are often held, discontinued, or changed to alternative administration r...

Background: Unused opioid prescriptions can be a driver of opioid misuse. Our objective was to determine the optimal quantity of opioids to prescribe to patients with acute pain at emergency department discharge, in order to meet their analgesic needs while limiting the amount of unused opioids. Methods: In a prospective, multicentre cohort study,...

Introduction Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulatio...

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40...

Background: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. Methods: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty...

BACKGROUND: Delirium is a common neurological complication in patients admitted to the intensive care unit (ICU) after moderate to severe traumatic brain injury (TBI). Although current clinical guidelines prioritize delirium prevention, no specific tool is tailored to detect early signs of delirium in TBI patients. This preliminary 2-phase observat...

Background In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitati...

Traumatic brain injury (TBI) survivors often suffer from agitated behaviors and will most likely receive pharmacological treatments. Choosing an optimal and safe treatment that will not interfere with neurological recovery remains controversial. By interfering with dopaminergic circuits, antipsychotics may impede processes important to cognitive re...

The objective of this study was to evaluate the exposure and the pharmacodynamic target attainment of piperacillin/tazobactam (PTZ) in adult critically ill patients. We conducted a prospective observational study in the intensive care unit (ICU) of the Hôpital du Sacré-Cœur de Montréal (a Level I trauma centre in Montreal, QC, Canada) between Janua...

Purpose Agitation is a common behavioural problem following traumatic brain injury (TBI). Intensive care unit (ICU) physicians’ perspectives regarding TBI-associated agitation are unknown. Our objective was to describe physicians’ beliefs and perceived importance of TBI-associated agitation in critically ill patients. Methods Following current sta...

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 describe the effect of valproic acid (VPA) as adjuvant treatment for agitation in the ICU, identify predictors of response to VPA and eva...

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...

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. We identified two patients with ARC and intermittent administration of...

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...

Background: Sedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summar...

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...