Use of actigraphy for monitoring agitation and rest-activity cycles in patients with acute traumatic brain injury in the ICU.

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 agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients. METHODS: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts. Feasibility was assessed by actigraphy recording duration and missing activity count per day. RESULTS: Data from 25 patients were analyzed. The mean number of completed day of actigraphy per patient was 6.5 ± 5.1. The mean missing activity count was 20.3 minutes (±81.7) per day. The mean level of activity measured by raw actigraphy counts per minute over 24 hours was higher in participants with agitation than without agitation. CONCLUSIONS: This study supports the feasibility of actigraphy use in TBI patients in the ICU. In the acute phase of TBI, agitated patients have higher levels of activity, confirming the potential of actigraphy to monitor agitation.

Flow-through imaging and automated analysis of oil-exposed early stage Atlantic cod (Gadus morhua).

Toxicology studies in early fish life stages serve an important function in measuring the impact of potentially harmful substances, such as crude oil, on marine life. Morphometric analysis of larvae can reveal the effects of such substances in retarding growth and development. These studies are labor intensive and time consuming, typically resulting in only a small number of samples being considered. An automated system for imaging and measurement of experimental animals, using flow-through imaging and an artificial neural network to allow faster sampling of more individuals, has been described previously and used in toxicity experiments. This study compares the performance of the automated imaging and analysis system with traditional microscopy techniques in measuring biologically relevant endpoints using two oil treatments as positive controls. We demonstrate that while the automated system typically underestimates morphometric measurements relative to analysis of manual microscopy images, it shows similar statistical results to the manual method when comparing treatments across most endpoints. It allows for many more individual specimens to be sampled in a shorter time period, reducing labor requirements and improving statistical power in such studies, and is noninvasive allowing for repeated sampling of the same population.

Impact of Ketamine on Analgosedative Consumption in Critically Ill Patients: A Systematic Review and Meta-Analysis.

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: critical care, ICU, ketamine, sedation, and anesthesia. All studies included the primary outcome of interest: daily opioid and/or sedative consumption. STUDY SELECTION AND DATA EXTRACTION: Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools. DATA SYNTHESIS: A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, -13.19 µg kg-1 h-1 morphine equivalents, 95% CI -22.10 to -4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation. CONCLUSION: Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations.

Safety of dexmedetomidine for the control of agitation in critically ill traumatic brain injury patients: a descriptive study.

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, anticonvulsants and sedative agents. Among sedatives, the safety and efficacy of dexmedetomidine to control agitation in traumatic brain injury patients is not well documented. OBJECTIVE: To describe the safety, use and efficacy of dexmedetomidine for the management of agitation following traumatic brain injury in the intensive care unit. METHODS: Medical records of all patients admitted to the intensive care unit of the Hôpital Sacré-Coeur de Montréal for a traumatic brain injury who received dexmedetomidine for agitation between 1 January 2017 and 31 December 2017 were reviewed. Patients who received dexmedetomidine for indications other than agitation were excluded. Data on dexmedetomidine prescription practices and safety were extracted. Frequency of agitation and concomitant psychoactive medication use was explored over a period starting two days prior to the initiation of dexmedetomidine to six days after or discontinuation, whichever came first. RESULTS: We identified 41 patients in whom dexmedetomidine was initiated. Dexmedetomidine was started on median ICU day 3 (25th -75th percentiles: 2-7) and had a median treatment duration of 3 days (25th -75th percentiles: 3-6) and a mean average rate of 0.62 mcg/kg/h (SD 0.25). Although hypotension (76%) and bradycardia (54%) were common, only one patient required intervention. The proportion of patients with at least one episode of agitation decreased from 100% on day 0, to 88%, 69% and 63% on days 1, 2 and 3 of dexmedetomidine, respectively. The decrease was statistically significant difference between days 0 and 2 as well as between days 0 and 3. Concomitant use of propofol and benzodiazepines also decreased over the course of dexmedetomidine treatment. CONCLUSION: Dexmedetomidine use was safe and associated with a reduction in agitation in traumatic brain injury patients in the 96 hours following its initiation.

Modifiable Risk Factors for Delirium in Critically Ill Trauma Patients: A Multicenter Prospective Study.

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 modifiable risk factors for delirium among trauma patients admitted to the ICU. DESIGN:: Prospective observational study. SETTING:: Two level 1 trauma ICU centers. PATIENTS:: Patients 18 years of age or older admitted for trauma including mild to moderate traumatic brain injury were eligible for the study. INTERVENTIONS AND MEASUREMENTS:: Delirium was assessed daily using the confusion assessment method for the ICU (CAM-ICU). The effect of modifiable risk factors was assessed using multivariate Cox regression analysis adjusting for severity of illness and significant nonmodifiable risk factors. MAIN RESULTS:: A total of 58 of 150 recruited patients (38.7%; 95% confidence interval [CI] 30.9-46.5) screened positive for delirium during ICU stay. When adjusting for significant nonmodifiable risk factors, physical restraints (hazard ratio [HR]: 2.13; 95% CI: 1.07-4.24) and active infection or sepsis (HR: 2.12; 95% CI: 1.18-3.81) significantly increased the risk of delirium, whereas opioids (HR: 0.35; 95% CI: 0.13-0.98), episodes of hypoxia (HR: 0.55; 95% CI: 0.31-0.95), access to a television/radio in the room (HR: 0.26; 95% CI: 0.11-0.62), and number of hours mobilized per day (HR: 0.77; 95% CI: 0.68-0.88) were associated with significantly less risk of delirium. CONCLUSION:: We have identified modifiable risk factors for delirium. Future studies should aim at implementing strategies to modify these risk factors and evaluate their impact on the risk of delirium.

Pharmacological interventions for the treatment of delirium in critically ill adults.

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 interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population. OBJECTIVES: Primary objective1. To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of deliriumSecondary objectivesTo assess the following:1. effects of pharmacological interventions on delirium-free and coma-free days; days with coma; delirium relapse; duration of mechanical ventilation; intensive care unit (ICU) and hospital length of stay; mortality; and long-term outcomes (e.g. cognitive; discharge disposition; health-related quality of life); and2. the safety of such treatments for critically ill adult patients. SEARCH METHODS: We searched the following databases from their inception date to 21 March 2019: Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO using the Ovid platform. We also searched the Cochrane Library on Wiley, the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/PROSPERO/), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. We performed a grey literature search of relevant databases and websites using the resources listed in Grey Matters developed by the Canadian Agency for Drugs and Technologies in Health (CADTH). We also searched trial registries and abstracts from annual scientific critical care and delirium society meetings. SELECTION CRITERIA: We sought randomized controlled trials (RCTs), including quasi-RCTs, of any pharmacological (drug) for treatment of delirium in critically ill adults. The drug intervention was to be compared to another active drug treatment, placebo, or a non-pharmacological intervention (e.g. mobilization). We did not apply any restrictions in terms of drug class, dose, route of administration, or duration of delirium or drug exposure. We defined critically ill patients as those treated in an ICU of any specialty (e.g. burn, cardiac, medical, surgical, trauma) or high-dependency unit. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies from the search results; four review authors (in pairs) performed data extraction and assessed risk of bias independently. We performed data synthesis through pairwise meta-analysis and network meta-analysis (NMA). Our hypothetical network structure was designed to be analysed at the drug class level and illustrated a network diagram of 'nodes' (i.e. drug classes) and 'edges' (i.e. comparisons between different drug classes from existing trials), thus describing a treatment network of all possible comparisons between drug classes. We assessed the quality of the body of evidence according to GRADE, as very low, low, moderate, or high. MAIN RESULTS: We screened 7674 citations, from which 14 trials with 1844 participants met our inclusion criteria. Ten RCTs were placebo-controlled, and four reported comparisons of different drugs. Drugs examined in these trials were the following: antipsychotics (n = 10), alpha2 agonists (n = 3; all dexmedetomidine), statins (n = 2), opioids (n = 1; morphine), serotonin antagonists (n = 1; ondansetron), and cholinesterase (CHE) inhibitors (n = 1; rivastigmine). Only one of these trials consistently used non-pharmacological interventions that are known to improve patient outcomes in both intervention and control groups.Eleven studies (n = 1153 participants) contributed to analysis of the primary outcome. Results of the NMA showed that the intervention with the smallest ratio of means (RoM) (i.e. most preferred) compared with placebo was the alpha2 agonist dexmedetomidine (0.58; 95% credible interval (CrI) 0.26 to 1.27; surface under the cumulative ranking curve (SUCRA) 0.895; moderate-quality evidence). In order of descending SUCRA values (best to worst), the next best interventions were atypical antipsychotics (RoM 0.80, 95% CrI 0.50 to 1.11; SUCRA 0.738; moderate-quality evidence), opioids (RoM 0.88, 95% CrI 0.37 to 2.01; SUCRA 0.578; very-low quality evidence), and typical antipsychotics (RoM 0.96, 95% CrI 0.64 to1.36; SUCRA 0.468; high-quality evidence).The NMAs of multiple secondary outcomes revealed that only the alpha2 agonist dexmedetomidine was associated with a shorter duration of mechanical ventilation (RoM 0.55, 95% CrI 0.34 to 0.89; moderate-quality evidence), and the CHE inhibitor rivastigmine was associated with a longer ICU stay (RoM 2.19, 95% CrI 1.47 to 3.27; moderate-quality evidence). Adverse events often were not reported in these trials or, when reported, were rare; pair-wise analysis of QTc prolongation in seven studies did not show significant differences between antipsychotics, ondansetron, dexmedetomidine, and placebo. AUTHORS' CONCLUSIONS: We identified trials of varying quality that examined six different drug classes for treatment of delirium in critically ill adults. We found evidence that the alpha2 agonist dexmedetomidine may shorten delirium duration, although this small effect (compared with placebo) was seen in pairwise analyses based on a single study and was not seen in the NMA results. Alpha2 agonists also ranked best for duration of mechanical ventilation and length of ICU stay, whereas the CHE inhibitor rivastigmine was associated with longer ICU stay. We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days, days with coma, physical restraint use, length of stay, long-term cognitive outcomes, or mortality. No studies reported delirium relapse, resolution of symptoms, or quality of life. The ten ongoing studies and the six studies awaiting classification that we identified, once published and assessed, may alter the conclusions of the review.

A systematic review of interventions to facilitate extubation in patients difficult-to-wean due to delirium, agitation, or anxiety and a meta-analysis of the effect of dexmedetomidine.

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 to wean patients that are difficult-to-wean from mechanical ventilation due to delirium, agitation, or anxiety. METHODS: A systematic review was performed using MEDLINE, EMBASE, and PubMed. Studies evaluating mechanically ventilated patients deemed difficult-to-wean due to delirium, agitation, or anxiety, and comparing the effects of an intervention with a comparator arm were sought. Time-to-extubation was the primary outcome while the secondary outcome was intensive care unit (ICU) length of stay. RESULTS: From 10,860 studies identified, eight met the inclusion criteria: six studies assessed dexmedetomidine while the remaining two assessed loxapine and biofeedback. Pooled analysis of studies assessing dexmedetomidine showed reduced time-to-extubation (six studies, n = 303) by 10.9 hr compared with controls (95% confidence interval [CI], -15.7 to -6.1; I2 = 68%) and ICU length of stay (four studies, n = 191) by 2.6 days (95% CI, 1.9 to 3.3; I2 = 0%). Nevertheless, the evidence was deemed to be of low quality given the small sample sizes and high heterogeneity. Studies assessing other interventions did not identify improvements compared with controls. Safety assessment was globally poorly reported. CONCLUSIONS: This systematic review and meta-analysis provides low quality evidence to suggest the use of dexmedetomidine in patients deemed difficult-to-wean due to agitation, delirium, or anxiety. Insufficient evidence was found regarding other interventions to provide any recommendation. TRIAL REGISTRATION: PROSPERO (CRD42016042528); registered 15 July, 2016.

RéSUMé: CONTEXTE: Le délirium, l'agitation et l'anxiété peuvent compliquer le sevrage de la ventilation mécanique et aboutir à une augmentation de la morbidité et du coût des soins de santé. L'approche clinique la plus adaptée au sevrage dans ces circonstances n'est pas claire et reste un défi pour les cliniciens. L'objectif de cette étude systématique était d'identifier des interventions efficaces et sécuritaires pour sevrer les patients « difficiles à sevrer ¼ de la ventilation mécanique en raison d'un délirium, d'une agitation ou d'anxiété. MéTHODES: Une revue systématique a été menée en utilisant les bases de données MEDLINE, EMBASE et PubMed. Les études évaluant des patients sous ventilation mécanique jugés difficiles à sevrer en raison d'un délirium, d'une agitation ou d'anxiété, comparant les effets d'une intervention à celle d'un bras comparateur ont été recherchées. Le critère d'évaluation principal a été le délai jusqu'à l'extubation et le critère d'évaluation secondaire a été la durée de séjour en unité de soins intensifs (USI). RéSULTATS: À partir de 10 860 études identifiées, huit satisfaisaient les critères d'inclusion : six études ont évalué la dexmédétomidine tandis que les deux dernières ont évalué la loxapine et le biofeedback. L'analyse groupée des études évaluant la dexmédétomidine a montré une réduction du délai d'extubation (six études, n = 303) de 10,9 heures comparativement aux contrôles (intervalle de confiance [IC] à 95 % : -15,7 à -6,1; I2 = 68 %) et de la durée du séjour en USI (quatre études, n = 191) de 2,6 jours (IC à 95 % : 1,9 à 3,3; I2 = 0 %). Néanmoins, les résultats sont de faible qualité compte tenu de la petite taille des échantillons et d'une grande hétérogénéité. Les études évaluant d'autres interventions n'ont pas identifié d'améliorations par rapport aux contrôles. D'une manière générale, les évaluations de l'innocuité ont été médiocrement décrites. CONCLUSIONS: Cette étude systématique et la méta-analyse procurent une preuve de qualité basse pour suggérer l'utilisation de la dexmédétomidine chez des patients considérés difficiles à sevrer en raison d'un délirium, d'une agitation ou d'anxiété. Les données probantes concernant les autres interventions ont été jugées insuffisantes pour permettre des recommandations quelconques. ENREGISTREMENT DE L'ESSAI CLINIQUE: PROSPERO (CRD42016042528); enregistré le 15 juillet 2016.

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.

A Single Mechanosensitive Channel Protects Francisella tularensis subsp. holarctica from Hypoosmotic Shock and Promotes Survival in the Aquatic Environment.

Francisella tularensis subsp. holarctica is found in North America and much of Europe and causes the disease tularemia in humans and animals. An aquatic cycle has been described for this subspecies, which has caused waterborne outbreaks of tularemia in at least 10 countries. In this study, we sought to identify the mechanosensitive channel(s) required for the bacterium to survive the transition from mammalian hosts to freshwater, which is likely essential for the transmission of the bacterium between susceptible hosts. A single 165-amino-acid MscS-type mechanosensitive channel (FtMscS) was found to protect F. tularensis subsp. holarctica from hypoosmotic shock, despite lacking much of the cytoplasmic vestibule domain found in well-characterized MscS proteins from other organisms. The deletion of this channel did not affect virulence within the mammalian host; however, FtMscS was required to survive the transition from the host niche to freshwater. The deletion of FtMscS did not alter the sensitivity of F. tularensis subsp. holarctica to detergents, H2O2, or antibiotics, suggesting that the role of FtMscS is specific to protection from hypoosmotic shock. The deletion of FtMscS also led to a reduced average cell size without altering gross cell morphology. The mechanosensitive channel identified and characterized in this study likely contributes to the transmission of tularemia between hosts by allowing the bacterium to survive the transition from mammalian hosts to freshwater.IMPORTANCE The contamination of freshwater by Francisella tularensis subsp. holarctica has resulted in a number of outbreaks of tularemia. Invariably, the contamination originates from the carcasses or excreta of infected animals and thus involves an abrupt osmotic downshock as the bacteria enter freshwater. How F. tularensis survives this drastic change in osmolarity has not been clear, but here we report that a single mechanosensitive channel protects the bacterium from osmotic downshock. This channel is functional despite lacking much of the cytoplasmic vestibule domain that is present in better-studied organisms such as Escherichia coli; this report builds on previous studies that have suggested that parts of this domain are dispensable for downshock protection. These findings extend our understanding of the aquatic cycle and ecological persistence of F. tularensis, with further implications for mechanosensitive channel biology.

Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management.

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-June 2017), and CINAHL (1982-June 2017) with the terms opioid withdrawal, opioid, opiate, critical care, critically ill, assessment tool, scale, taper, weaning, and management. Reference list of identified literature was searched for additional references as well as www.clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION: We restricted articles to those in English and dealing with humans. DATA SYNTHESIS: We identified 2 validated pediatric critically ill opioid withdrawal assessment tools: (1) Withdrawal Assessment Tool-Version 1 (WAT-1) and (2) Sophia Observation Withdrawal Symptoms Scale (SOS). Neither tool differentiated between opioid and benzodiazepine withdrawal. WAT-1 was evaluated in critically ill adults but not found to be valid. No other adult tool was identified. For management, we identified 5 randomized controlled trials, 2 prospective studies, and 2 systematic reviews. Most studies were small and only 2 studies utilized a validated assessment tool. Enteral methadone, α-2 agonists, and protocolized weaning were studied. CONCLUSION: We identified 2 validated assessment tools for pediatric intensive care unit patients; no valid tool for adults. Management strategies tested in small trials included methadone, α-2 agonists, and protocolized sedation/weaning. We challenge researchers to create validated tools assessing specifically for opioid withdrawal in critically ill children and adults to direct management.

Drug-induced thrombocytopenia in the critically ill: a case-control study.

BACKGROUND: Drugs are suspected when obvious causes of intensive care unit (ICU)-acquired thrombocytopenia have been excluded. It has been estimated that 10% to 25% of cases may be drug induced. OBJECTIVES: The objectives of this study were to evaluate the risk of thrombocytopenia associated with drug classes commonly used in the ICU. METHODS: Data concerning patients admitted for more than 48 hours between 1997 and 2011 were extracted from a research-purpose database. Patients with thrombocytopenia within the first 72 hours of admission and with diagnoses or interventions considered strongly associated with thrombocytopenia were excluded. Drug exposures were compared and adjusted for confounders using conditional logistic regression. RESULTS: A total of 238 cases were identified after exclusions. Each case was matched according to sex, age, admission year, and admission unit with 1 control. In univariate analysis, quinolones (odds ratio [OR] = 1.56; 95% CI = 1.01-2.40) and extended spectrum ß-lactams (OR = 1.71; 95% CI = 1.00-2.93) were significantly associated with an increased risk of thrombocytopenia. After adjusting for confounders, exposure to quinolones was the only drug class with a statistically significant increase in risk of thrombocytopenia (OR = 1.697; 95% CI = 1.002-2.873; P = 0.049). CONCLUSION: In this study of ICU-acquired thrombocytopenia, we found no association between the exposures to several antibiotic classes, anticonvulsants, antiplatelet agents, nonsteroidal anti-inflammatory agents, and heparins and thrombocytopenia. As linezolid was not studied, no conclusions can be drawn concerning this agent. The statistically significant association between quinolones and thrombocytopenia warrants further investigation.

Albumin administration is associated with acute kidney injury in cardiac surgery: a propensity score analysis.

INTRODUCTION: The risk of acute kidney injury (AKI) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. We evaluated the adjusted risk of AKI associated with colloids following cardiac surgery. METHODS: We performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. We assessed crystalloid and colloid administration until 36 hours after surgery. AKI was defined by the RIFLE (risk, injury, failure, loss and end-stage kidney disease) risk and Acute Kidney Injury Network (AKIN) stage 1 serum creatinine criterion within 96 hours after surgery. RESULTS: Our cohort included 984 patients with a baseline glomerular filtration rate of 72 ± 19 ml/min/1.73 m(2). Twenty-three percent had a reduced left ventricular ejection fraction (LVEF), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0% based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10% and transfusions. There was an important dose-dependent AKI risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for AKI. To address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. In this analysis, albumin was associated with an increased AKI risk (RIFLE risk: 12% versus 5%, P = 0.03; AKIN stage 1: 28% versus 13%, P = 0.002). We repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and AKI. CONCLUSIONS: Albumin administration was associated with a dose-dependent risk of AKI and remained significant using a propensity score methodology. Future studies should address the safety of albumin-containing fluids on kidney function in patients undergoing cardiac surgery.

Predictors of physical restraint use in Canadian intensive care units.

INTRODUCTION: Physical restraint (PR) use in the intensive care unit (ICU) has been associated with higher rates of self-extubation and prolonged ICU length of stay. Our objectives were to describe patterns and predictors of PR use. METHODS: We conducted a secondary analysis of a prospective observational study of analgosedation, antipsychotic, neuromuscular blocker, and PR practices in 51 Canadian ICUs. Data were collected prospectively for all mechanically ventilated adults admitted during a two-week period. We tested for patient, treatment, and hospital characteristics that were associated with PR use and number of days of use, using logistic and Poisson regression respectively. RESULTS: PR was used on 374 out of 711 (53%) patients, for a mean number of 4.1 (standard deviation (SD) 4.0) days. Treatment characteristics associated with PR were higher daily benzodiazepine dose (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00 to 1.11), higher daily opioid dose (OR 1.04, 95% CI 1.01 to 1.06), antipsychotic drugs (OR 3.09, 95% CI 1.74 to 5.48), agitation (Sedation-Agitation Scale (SAS) >4) (OR 3.73, 95% CI 1.50 to 9.29), and sedation administration method (continuous and bolus versus bolus only) (OR 3.09, 95% CI 1.74 to 5.48). Hospital characteristics associated with PR indicated patients were less likely to be restrained in ICUs from university-affiliated hospitals (OR 0.32, 95% CI 0.17 to 0.61). Mainly treatment characteristics were associated with more days of PR, including: higher daily benzodiazepine dose (incidence rate ratio (IRR) 1.07, 95% CI 1.01 to 1.13), daily sedation interruption (IRR 3.44, 95% CI 1.48 to 8.10), antipsychotic drugs (IRR 15.67, 95% CI 6.62 to 37.12), SAS <3 (IRR 2.62, 95% CI 1.08 to 6.35), and any adverse event including accidental device removal (IRR 8.27, 95% CI 2.07 to 33.08). Patient characteristics (age, gender, Acute Physiology and Chronic Health Evaluation II score, admission category, prior substance abuse, prior psychotropic medication, pre-existing psychiatric condition or dementia) were not associated with PR use or number of days used. CONCLUSIONS: PR was used in half of the patients in these 51 ICUs. Treatment characteristics predominantly predicted PR use, as opposed to patient or hospital/ICU characteristics. Use of sedative, analgesic, and antipsychotic drugs, agitation, heavy sedation, and occurrence of an adverse event predicted PR use or number of days used.

Analgesic, sedative, antipsychotic, and neuromuscular blocker use in Canadian intensive care units: a prospective, multicentre, observational study.

PURPOSE: Our aim was to describe analgo-sedation and antipsychotic and neuromuscular blocking drug (NMBD) use in critically ill patients, management strategies, and variables associated with these practice patterns. METHODS: This prospective observational study in 51 intensive care units (ICUs) included all patients who underwent invasive mechanical ventilation (MV) over a two-week period during 2008-2009. RESULTS: We included 712 patients representing 3,620 patient-days. Median MV duration was 3.0 days (interquartile range 2-6). During MV, 92% of patients received analgo-sedation, 32% an adjunct agent (e.g., acetaminophen), 18% NMBDs, and 10% antipsychotics. Opioids were used more frequently than benzodiazepines or propofol (84.8% vs 62.2% vs 10.1% patients, respectively, P < 0.0001). Independent predictors of opioid and benzodiazepine use were a longer MV duration, assessment scales, physical restraints, and university-affiliated hospital. Although more than 50% of ICUs reported that assessment tools, protocols, and daily sedation interruption (DSI) were available for use, application was modest: sedation scale 53.0%, pain scale 19.1%, delirium scale 5.2%, protocol 25.0%, DSI 42.1%. Accidental device removal occurred in 4.6% of patients, with 75.8% of events during DSI. Daily sedation interruption was associated with protocol use, physical restraints, university-affiliated hospital, and short-duration MV. Variables associated with protocol use included assessment scales, longer MV duration, lack of physical restraints, and admission to a community hospital. CONCLUSION: Nearly all MV patients received analgo-sedation. Opioids were used more often than sedatives despite infrequent use of pain scales. Few patients received antipsychotic therapy, but physical restraint was common. Protocol use was poor compared to DSI. Duration of MV predicted the use of either.

Cognitive and Motor Function Effects of Antipsychotics in Traumatic Brain Injury: A Systematic Review of Pre-Clinical Studies.

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 recovery. Despite their frequent use, there have been no large randomized controlled studies of antipsychotics for the management of agitated behaviors during the acute TBI recovery period. We conducted a systematic review and meta-analysis of pre-clinical studies evaluating the effects of antipsychotics post-TBI on both cognitive and motor recovery. MEDLINE and Embase databases were searched up to August 2, 2023. Pre-clinical studies evaluating the effects of antipsychotics on cognitive and motor functions post-TBI were considered. Risk of bias was evaluated with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified 15 studies including a total of 1188 rodents, mostly conducted in male Sprague-Dawley rats using cortical impact injury. The analysis revealed no consistent effect of haloperidol on motor functions, but risperidone was associated with a significant impairment in motor function on day 5 post-injury (7.05 sec; 95% confidence interval [CI]: 1.47, 12.62; I2 = 92%). Other atypical antipsychotics did not result in impaired motor function. When evaluating cognitive function, haloperidol- (23.00 sec; 95% CI: 17.42-28.59; I2 = 7%) and risperidone-treated rats (24.27 sec; 95% CI: 16.18-32.36; I2 = 0%) were consistently impaired when compared to controls. In studies evaluating atypical antipsychotics, no impairments were observed. Clinicians should avoid the regular use of haloperidol and risperidone, and future human studies should be conducted with atypical antipsychotics.

Thrombocytopenia in the critically ill: prevalence, incidence, risk factors, and clinical outcomes.

PURPOSE: The aim of this cohort study was to describe the prevalence, incidence, and risk factors for thrombocytopenia in the intensive care unit (ICU) and to evaluate the impact of thrombocytopenia on mortality with further comparisons amongst major diagnostic categories. METHODS: Patients admitted to the ICU from 1997-2011 for cardiac, medical, surgical, and trauma conditions were included. The presence of a platelet count < 100 × 10(9)·L(-1) on admission day or its appearance during ICU stay were considered as prevalent and incident thrombocytopenia, respectively. Risk factors for thrombocytopenia and the influence of thrombocytopenia on mortality were also analyzed. RESULTS: This study included 20,696 patients. Prevalent and incident thrombocytopenia occurred in 13.3% and 7.8% of patients, respectively, with associated mortality rates of 14.3% and 24.7%, respectively, compared with 10.2% in the group with normal platelet count (P < 0.001). After adjustments, thrombocytopenia remained associated with an increased risk of mortality (odds ratio 1.25; 95% confidence interval 1.20 to 1.31; P < 0.001). The greatest impact of thrombocytopenia on mortality was observed in the cancer, respiratory, digestive, genitourinary, and infectious diagnostic categories. Independent risk factors included age, female sex, admission platelet counts and hemoglobin, mechanical ventilation, days of hospitalization prior to ICU admission, liver cirrhosis, hypersplenism, coronary bypass grafting, intra-aortic balloon pump placement, acute hepatitis, septic shock, and pulmonary embolism or deep vein thrombosis. CONCLUSIONS: Thrombocytopenia in the ICU is associated with an independent risk of mortality that varies greatly depending on diagnostic admission category.

Pharmacokinetics of Commonly Used Antimicrobials in Critically Ill Pediatric Patients During Extracorporeal Membrane Oxygenation: A Systematic Review.

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 to delineate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in critically ill neonates and children requiring ECMO therapy. METHODS: Medline, EMBASE, Global Health and All EBM Reviews databases were queried. Grey literature was examined. All clinical studies reporting PK/PD parameters of antimicrobials in critically ill pediatric patients treated with ECMO were included, except for case reports and congress abstracts. Two independent reviewers applied the inclusion and exclusion criteria. Reviewers were then paired to independently extract data and evaluate the methodological quality of studies using the ROBINS-I tool and the compliance with ClinPK reporting guidelines. Patient and study characteristics, key PK/PD findings, details of ECMO circuits and co-treatments were summarized qualitatively. Broad dosing recommendations were formulated based on the available data for specific antimicrobials. RESULTS: Twenty-nine clinical studies were included; most were observational and uncontrolled. Patient characteristics and co-treatments were often missing. The effect of ECMO on PK/PD parameters of antimicrobials varied depending on the drugs and population studied. It was only possible to formulate dosing recommendations for a few antimicrobials given the paucity of data, its overall low quality and heterogeneity in reporting. CONCLUSION: Limited data exists on the PK/PD of antimicrobials during ECMO therapy in the pediatric population. Rigorously designed population PK studies are required to establish empiric dosing guidelines for antimicrobials in patients requiring this therapeutic modality. The use of therapeutic drug monitoring for antimicrobials in pediatric patients on ECMO should be encouraged to optimize dosing. TRIAL REGISTRY: PROSPERO registration number: CRD42018099992 (Registered: July 24th 2018).

Clostridioides difficile infection in mechanically ventilated critically ill patients: A nested cohort study.

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 placebo. We adjudicated cases of CDI using standardized definitions, assessed timing (pre-ICU, in ICU, post-ICU) and severity. We analyzed risk factors and outcomes. RESULTS: Of 2650 patients, 86 were diagnosed with CDI during 90,833 hospital-days (0.95/1000 hospital-days); CDI prevalence was 3.2%. CDI incidence varied in timing; 0.3% patients had CDI pre-ICU, 2.2% in the ICU; an 0.8% developed CDI post-ICU. Relapse or recurrence of CDI was documented in 9.3% patients. Infections were mild/moderate in severity. Complications included septic shock (26.7%), organ failure (16.3%), and toxic megacolon requiring colectomy (1.2%). No risk factors for CDI were identified. CDI was not associated with hospital mortality. The duration of hospital stay was longer for those who had CDI compared those who did not, CONCLUSION: CDI was uncommon, severity was mild to moderate and not associated with mortality however CDI was associated with a longer hospital stay.

Canadian survey of critical care pharmacists' views and involvement in clinical research.

BACKGROUND: The involvement of Canadian critical care pharmacists in clinical research is not well documented. OBJECTIVE: To describe the clinical research experience of Canadian critical care pharmacists, describe their views about clinical research, and identify factors that facilitate their involvement in clinical research. METHODS: A cross-sectional electronic survey of Canadian critical care pharmacists was developed through an iterative process and conducted from July to October 2010. We invited 325 pharmacists from 129 hospitals across Canada to participate. Surveys with more than 30% of questions unanswered were discarded. RESULTS: Analyzable response rate was 66.2%. Overall, 33 pharmacists (15.7%) were highly involved in research, 54 (25.7%) were moderately involved, and 123 (58.6%) were minimally involved. Most respondents (97.2%) believed that critical care pharmacist involvement in research was desirable, and many (80.4%) expressed interest to be more involved in research. Nearly all respondents (99.5%) agreed that more support should be provided to pharmacists interested in conducting research. Pharmacists currently involved in research have obtained higher academic degrees (adjusted OR 11.23; p < 0.001), express a strong interest in research (adjusted OR 7.44; p < 0.001), report a higher level of training for involvement in research (adjusted OR 2.23; p = 0.047), and practice more often in a university hospital (adjusted OR 3.68; p = 0.004) within an intensive care unit where involvement in research is valued (adjusted OR 5.61; p < 0.001). Support from pharmacy departments is not related to involvement in research (adjusted OR 1.22; p = 0.633). CONCLUSIONS: Canadian critical care pharmacists are involved to varying degrees in clinical research and are very interested in initiating and supporting research activities. Opportunities are present but significant barriers exist. The value of pharmacist-initiated research needs recognition as a priority within hospital pharmacy administration.

A flow-through imaging system for automated measurement of ichthyoplankton.

Microscopic imaging and morphometric measurement of fish embryos and larvae is essential in environmental monitoring of fish populations and to evaluate larvae development in aquaculture. Traditional microscopy methods require time-consuming, repetitive work by human experts. We present a method for fast imaging and analysis of millimetre-scale ichthyoplankton suspended in seawater. Our system can be easily built from common and off-the-shelf components and uses open-source software for image capture and analysis. Our system obtains images of similar quality to traditional microscopy, and biological measurements comparable to those by human experts, with minimal human interaction. This saves time and effort, while increasing the size of data sets obtained. We demonstrate our approach with cod eggs and larvae, and present results showing biologically relevant endpoints including egg diameter, larval standard length, yolk volume and eye diameter, with comparison to similar measurements reported in the literature. • High throughput, microscope-scale imaging of fish eggs and larvae • Automated measurement of biologically relevant endpoints • Easily built from off-the-shelf components and open-source software.