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To study the incidence, predictors, and outcomes of diarrhea during the stay in the intensive care unit (ICU).Prospective cohort of consecutive adults in the ICU for 24 h during a 10-week period across 12 intensive care units (ICUs) internationally. The explored outcomes were: (1) incidence of diarrhea, (2) Clostridioides difficile-associated diarrhea (CDAD); (3) ICU and hospital length of stay (LOS) and mortality in patients with diarrhea. We fit generalized linear models to evaluate the predictors, management, morbidity and mortality associated with diarrhea.Among 1109 patients aged 61.4 (17.5) [mean (standard deviation)] years, 981(88.5%) were medical and 645 (58.2%) were mechanically ventilated. The incidence was 73.8% (818 patients, 73.8%, 95% confidence interval [CI] 71.1-76.6) using the definition of the World Health Organisation (WHO). Incidence varied across definitions (Bristol 53.5%, 95% CI 50.4-56.7; Bliss 37.7%, 95% CI 34.9-40.4). Of 99 patients with diarrhea undergoing CDAD testing, 23 tested positive (2.2% incidence, 95% CI 1.5-3.4). Independent predictors included enteral nutrition (RR 1.23, 95% CI 1.16-1.31, p 0.001), antibiotic days (RR 1.02, 95% CI 1.02-1.03, p 0.001), and suppositories (RR 1.14 95% CI 1.06-1.22, p 0.001). Opiates decreased diarrhea risk (RR 0.76, 95% CI 0.68-0.86, p 0.001). Diarrhea prompted management modifications (altered enteral nutrition or medications: RR 10.25, 95% CI 5.14-20.45, p 0.001) or other consequences (fecal management device or CDAD testing: RR 6.16, 95% CI 3.4-11.17, p 0.001). Diarrhea was associated with a longer time to discharge for ICU or hospital stay, but was not associated with hospital mortality.Diarrhea is common, has several predictors, and prompts changes in patient care, is associated with longer time to discharge but not mortality.

Purpose To assess the feasibility of a trial evaluating whether hyperoncotic albumin, in addition to diuretics, improves diuresis and facilitates liberation from mechanical ventilation in critically ill adults. Materials and methods We randomized 46 hemodynamically stable patients with hypoalbuminemia, prescribed diuretics by treating clinicians, to receive 100 mL of 25% albumin or 0.9% saline placebo BID, for three days, in blinded fashion. We chose five feasibility measurements: enrolment of 50% of eligible patients, at least one patient/week; administration of study treatment within 2 h of diuretics in 85% of patients; completion of study regimen in 80% of patients; and avoidance of open label albumin in 85% of patients. Clinical outcomes included fluid balance, ventilator-free days, and mortality. Results We randomized 85% of eligible patients. Eighty-four percent received study treatment within 2 h of diuretics, 69% received all doses of study treatment. Study treatment was held in the albumin and placebo groups because of no further need for diuresis (4 vs. 1), hypotension (2 v. 4), and albumin > 35 (1 v. 0). Twenty percent of patients received open-label albumin. Clinical outcomes were similar between groups. Conclusions The current study design did not demonstrate feasibility, but can inform the design of a definitive trial.

IntroductionComa is a deep state of unconsciousness that can be caused by a variety of clinical conditions. Traditional tests for coma outcome prediction are based mainly on a set of clinical observations. Recently, certain event-related potentials (ERPs), which are transient electroencephalogram (EEG) responses to auditory, visual or tactile stimuli, have been introduced as useful predictors of a positive coma outcome (ie, emergence). However, such tests require the skills of clinical neurophysiologists, who are not commonly available in many clinical settings. Additionally, none of the current standard clinical approaches have sufficient predictive accuracies to provide definitive prognoses.ObjectiveThe objective of this study is to develop improved machine learning procedures based on EEG/ERP for determining emergence from coma.Methods and analysisData will be collected from 50 participants in coma. EEG/ERP data will be recorded for 24 consecutive hours at a maximum of five time points spanning 30 days from the date of recruitment to track participants’ progression. The study employs paradigms designed to elicit brainstem potentials, middle-latency responses, N100, mismatch negativity, P300 and N400. In the case of patient emergence, data are recorded on that occasion to form an additional basis for comparison. A relevant data set will be developed from the testing of 20 healthy controls, each spanning a 15-hour recording period in order to formulate a baseline. Collected data will be used to develop an automated procedure for analysis and detection of various ERP components that are salient to prognosis. Salient features extracted from the ERP and resting-state EEG will be identified and combined to give an accurate indicator of prognosis.Ethics and disseminationThis study is approved by the Hamilton Integrated Research Ethics Board (project number 4840). Results will be disseminated through peer-reviewed journal articles and presentations at scientific conferences.Trial registration numberNCT03826407.

IntroductionDiarrhoea is a frequent concern in the intensive care unit (ICU) and is associated with prolonged mechanical ventilation, increased length of ICU stay, skin breakdown and renal dysfunction. However, its prevalence, aetiology and prognosis in the critically ill have been poorly studied. The primary objectives of this study are to determine the incidence, risk factors and consequences of diarrhoea in critically ill adults. The secondary objectives are to estimate the incidence ofClostridium difficile-associated diarrhoea (CDAD) in ICU patients and to validate the Bristol Stool Chart and Bliss Stool Classification System characterising bowel movements in the ICU. Our primary outcome is the incidence of diarrhoea . Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay.Methods and analysisThis international prospective cohort study will enrol patients over 10 weeks in 12 ICUs in Canada, the USA, Poland and Saudi Arabia. We will include all patients 18 years of age and older who are admitted to the ICU for at least 24 hours and follow them daily until ICU discharge. Our primary outcome is the incidence of diarrhoea based on the WHO definition, during the ICU stay. Our secondary outcomes include: CDAD, ICU and hospital mortality and ICU and hospital length of stay. We will use logistic regression to identify factors associated with diarrhoea (as defined using WHO criteria) and the kappa statistic to measure agreement on diarrhoea rates between the WHO definition and the Bristol Stool Chart and Bliss Stool Classification System.Ethics and disseminationThe protocol has been approved by the research ethics board of all participating centres. The diarrhoea interventions, consequences and epidemiology in the intensive care unit (DICE-ICU) study will generate evidence about diarrhoea and its frequency, predisposing factors and consequences, to inform critical care practice and future research.Lay summaryDiarrhoea is a frequent clinical problem for hospitalised patients including those who are critically ill in the ICU. Diarrhoea can cause complications such as skin damage, dehydration and kidney problems. It is not clear how common diarrhoea is in the ICU, the factors that cause it or the best way for clinicians to assess it. The DICE-ICU study is an international prospective observational study to examine the frequency, risk factors and outcomes of diarrhoea during critical illness.

During an interdisciplinary Canadian leadership forum [ www.ice-ccm.org (click on the Conferences icon)], participants were challenged to develop an approach to a difficult leadership/management situation. In a scenario involving aggressive behavior among health care providers, participants identified that, before responding, an appropriate leader should collect additional information to identify the core problem(s) causing such behavior. Possibilities include stress; lack of clear roles, responsibilities, and standard operating procedures; and, finally, lack of training on important leadership/management skills. As a result of these core problems, several potential solutions are possible, all with potential obstacles to implementation. Additional education around communication and team interaction was felt to be a priority. In summary, clinical leaders probably have a great deal to gain from augmenting their leadership/management skills.

Background In critically ill patients who are receiving mechanical ventilation, the factors associated with physicians' decisions to withdraw ventilation in anticipation of death are unclear. The objective of this study was to examine the clinical determinants that were associated with the withdrawal of mechanical ventilation. Methods We studied adults who were receiving mechanical ventilation in 15 intensive care units, recording base-line physiological characteristics, daily Multiple Organ Dysfunction Scores, the patient's decision-making ability, the type of life support administered, the use of do-not-resuscitate orders, the physician's prediction of the patient's status, and the physician's perceptions of the patient's preferences about the use of life support. We examined the relation between these factors and withdrawal of mechanical ventilation, using Cox proportional-hazards regression analysis. Results Of 851 patients who were receiving mechanical ventilation, 539 (63.3 percent) were successfully weaned, 146 (17.2 percent) died while receiving mechanical ventilation, and 166 (19.5 percent) had mechanical ventilation withdrawn. The need for inotropes or vasopressors was associated with withdrawal of the ventilator (hazard ratio, 1.78; 95 percent confidence interval, 1.20 to 2.66; P=0.004), as were the physician's prediction that the patient's likelihood of survival in the intensive care unit was less than 10 percent (hazard ratio, 3.49; 95 percent confidence interval, 1.39 to 8.79; P=0.002), the physician's prediction that future cognitive function would be severely impaired (hazard ratio, 2.51; 95 percent confidence interval, 1.28 to 4.94; P=0.04), and the physician's perception that the patient did not want life support used (hazard ratio, 4.19; 95 percent confidence interval, 2.57 to 6.81; P Conclusions Rather than age or the severity of the illness and organ dysfunction, the strongest determinants of the withdrawal of ventilation in critically ill patients were the physician's perception that the patient preferred not to use life support, the physician's predictions of a low likelihood of survival in the intensive care unit and a high likelihood of poor cognitive function, and the use of inotropes or vasopressors.

Fluid retention is a common complication of critical illness. It typically results from large-volume fluid infusions during acute resuscitation and is worsened by hypoalbuminemia. Recognized as edema, fluid retention is important for its association with delayed weaning and increased mortality. The standard treatment is the administration of diuretics, with or without albumin. We hypothesize that intravenous 25% albumin plus furosemide, by comparison with furosemide alone, improves diuresis, oxygenation, and hemodynamic stability in the deresuscitation of critically ill, hypoalbuminemic patients. We propose a pilot study to determine the feasibility of a trial to investigate this hypothesis. FADE is a single-center, parallel, pilot randomized controlled trial. We aim to allocate 50 hemodynamically stable, hypoalbuminemic adult patients receiving diuresis to treatment with either 100 ml of either 25% albumin or normal saline placebo twice daily, for a total of six doses. Diuretics are to be prescribed by the caregiving team at least twice daily, and administered within 2 hours following study treatment. Patients, intensive care unit (ICU) clinicians, data collectors, and outcome adjudicators will be blinded to treatment allocation. Feasibility outcome measures include the proportion of patients receiving albumin within 2 hours of diuretic, the proportion of patients receiving the full six doses of study treatment, the proportion of patients who receive open label 25% albumin, and the rate of recruitment. Physiologic, laboratory, and clinical data are collected until discharge from the ICU or until 30 days. This is the first randomized trial to assess the use of hyperoncotic albumin in addition to diuretics in a general ICU population. Should this pilot study demonstrate feasibility, the primary outcome measure of the larger clinical trial will be the number of ventilator-free days, with secondary clinical outcome measures of duration of mechanical ventilation, length of ICU stay, episodes of hemodynamic instability and mortality. The addition of 25% albumin to standard diuretic therapy is a promising treatment in the post-resuscitation care of the critically ill patient. ClinicalTrials.gov NCT02055872 ; ISRCTN70191881 .

Background: Perceptions about functional and employment status before admission to the intensive care unit (ICU) may influence how patients and clinicians make decisions about cardiopulmonary resuscitation. Objective: To examine the relationship between cardiopulmonary resuscitation directives established within 24 hours of admission to the ICU and clinical perceptions of premorbid functional and employment status. Design: Prospective observational study in 15 university-affiliated centers in Canada, the United States, Australia, and Sweden. Patients: A total of 1,008 ICU patients aged 18 years or older expected to stay in the ICU at least 72 hours. Measurements: By using multinomial logistic regression, we examined the relationship between functional status and employment status perceived by the ICU team 1 month before ICU admission (the independent variables) and resuscitation status (the dependent variable). Each patient had either an explicit resuscitation directive (to resuscitate or not to resuscitate), or an implicit resuscitation directive to resuscitate. Results: On average, patients were 61.7 years (±17.4 y) old with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 21.5 (±8.7); 846 (83.9%) were ventilated mechanically within 48 hours and 345 (34.2%) died in the ICU. Most patients (793, 78.7%) had no explicit resuscitation directive; 98 (9.7%) had an explicit plan to resuscitate, whereas 117 (11.6%) had an explicit plan of do-not-resuscitate. Of 1,008 patients, 98 (9.7%) were severely functionally limited, 217 (21.5%) were somewhat limited, 628 (62.3%) were totally independent, and 65 (6.4%) had unknown functional status 1 month before ICU admission. Severe functional status impairment was associated moderately with an explicit plan to resuscitate (odds ratio, 2.2 relative to no explicit directive) and associated strongly with an explicit do-not-resuscitate plan (odds ratio, 6.2 relative to no explicit directive, P value on the difference = .011). This relationship was not influenced by age, sex, APACHE II score, medical or surgical status, admission diagnosis, employment status, or city. However, severe functional status was associated strongly and significantly with an explicit do-not-resuscitate directive among those who could not participate in decision making (odds ratio, 8.2; 95% confidence interval, 4.5–15.0), and more weakly associated in those who could participate (odds ratio, 1.7; 95% confidence interval, 0.3–8.6). Being unemployed was associated with an increased odds of an explicit resuscitation directive versus no explicit directive (odds ratio, 5.5; 95% confidence interval, 2.2–13.4). Conclusions: Functional status impairment perceived by the ICU team is associated clearly with do-not-resuscitate directives in patients unable to participate in decision making. However, the association appears much weaker in patients able to participate in decision making. Patients’ perceived employment status also may influence resuscitation decisions. Our results emphasize the challenges of ensuring that crucial resuscitation decisions are not affected adversely by patients’ inability to participate in decisions, and by their functional and employment status.

Background The administration of antiplatelet drugs before coronary artery bypass graft surgery (CABG) is associated with an increased risk of major hemorrhage and related surgical reexploration. Little is known about the relative effect of combined clopidogrel and aspirin on blood product use around the time of CABG. We evaluated the associated risk between the combined use of aspirin and clopidogrel and the transfusion of blood products perioperatively. Methods We retrospectively studied a cohort of 659 individuals who underwent a first CABG, without concomitant valvular or aortic surgery, at a single large Canadian cardiac surgical centre between January 2000 and April 2002. The four study exposure groups were those prescribed aspirin (n = 105), clopidogrel (n = 11), the combination of both (n = 46), or neither drug (n = 497), within 7 days prior to CABG. The primary study outcome was the excessive transfusion of blood products during CABG and up to the second post-operative day, defined as ≥ 2 units of packed red blood cells (PRBC), ≥ 2 units of fresh frozen plasma, ≥ 5 units of cryoprecipitate or ≥ 5 units of platelets. Secondary outcomes included the mean number of transfused units of each type of blood product. Results A greater mean number of units of PRBC were transfused among those who received clopidogrel alone (2.9) or in combination with aspirin (2.4), compared to those on aspirin alone (1.9) or neither antiplatelet drug (1.4) (P = 0.001). A similar trend was seen for the respective mean number of transfused units of platelets (3.6, 3.7, 1.3 and 1.0; P < 0.001) and fresh frozen plasma (2.5, 3.1, 2.3, 1.6; P = 0.01). Compared to non-users, the associated risk of excessive blood product transfusion was highest among recipients of aspirin and clopidogrel together (adjusted OR 2.2, 95% CI 1.1–4.3). No significant association was seen among lone users of aspirin (adjusted OR 1.0, 95% CI 0.6–1.6) or clopidogrel (adjusted OR 0.7, 95% CI 0.2–2.5), compared to non-users. Conclusions While combined use of aspirin and clopidogrel shortly before CABG surgery may increase the associated risk of excess transfusion of blood products perioperatively, several study limitations prevent any confident conclusions from being drawn. Beyond challenging these findings, future research might focus on the value of both intraoperative monitoring of platelet function, and the effectiveness of antifibrinolytic agents, at reducing the risk of postoperative bleeding.

Intensive insulin therapy has recently been shown to decrease morbidity and mortality in the critically ill population in a large randomized clinical trial. To determine the beliefs and attitudes of ICU clinicians about glycemic control. Self-administered survey. ICU nurses and physicians in five university-affiliated multidisciplinary ICUs. A total of 317 questionnaires were returned from 233 ICU nurses and 84 physicians. The reported clinically important threshold for hypoglycemia was 4 mmol/l (median, IQR 3–4 mmol/l). In non-diabetic patients, the clinically important threshold for hyperglycemia was 10 mmol/l (IQR 9–12 mmol/l); however, nurses had a significantly higher threshold than physicians (difference of 0.52 mmol/l (95% CI 0.09–0.94 mmol/l, P=0.018). In diabetic patients, the clinically important threshold for hyperglycemia was also 10 mmol/l (IQR 10–12 mmol/l), and again nurses had a significantly higher threshold than physicians (0.81 mmol/l, 95% CI 0.29–1.32 mmol/l, P=0.0023). Avoidance of hyperglycemia was judged most important for diabetic patients (87.7%, 95% CI 84.1–91.3%), patients with acute brain injury (84.5%, 95% CI 80.5–88.5%), patients with a recent seizure (74.4%, 95% CI 69.6–79.3%), patients with advanced liver disease (64.0%, 95% CI 58.7–69.3%), and for patients with acute myocardial infarction (64.0%, 95% CI 58.7–69.3%). Physicians expressed more concern than nurses about avoiding hyperglycemia in patients with acute myocardial infarction (P=0.0004). ICU clinicians raised concerns about the accuracy of glucometer measurements in critically ill patients (46.1%, 95% CI 40.5–51.6%). Attention to these beliefs and attitudes could enhance the success of future clinical, educational and research efforts to modify clinician behavior and achieve better glycemic control in the ICU setting.

Objective To evaluate whether measurement of the hemoglobin (Hb) concentration with a blood gas analyzer approximates that determined by a conventional coulter counter in critically ill adults.

Both exercise and histamine inhalation cause bronchoconstriction in asthmatic subjects. Repeated challenges with both stimuli cause less bronchoconstriction. Exercise refractoriness and histamine tachyphylaxis may occur through release of inhibitory mediators in the airways. The purpose of this study was to determine whether prior challenge with exercise or histamine reduced the subsequent bronchoconstriction to the opposite challenge. Eight asthmatic subjects with exercise bronchoconstriction were studied on 4 study days. On each study day, two consecutive tests were separated by 1 h as follows: on Day 1, two exercise challenges; on Day 2, two histamine inhalation tests; on Days 3 and 4, a histamine test was followed by an exercise challenge or an exercise challenge was followed by a histamine test. On Day 1, the mean fall in the FEV1 after the initial exercise challenge was 22.13% (SD, 7.12%); after the second exercise challenge, 1 h later, it was 11.13% (SD, 10.69%) (p less than 0.005). On Day 2, the provocative concentration of histamine causing a 20% fall in FEV1 (PC20) was 1.68 mg/ml (%SD, 2.02) for the first test and 2.68 mg/ml (%SD, 1.99) for the second test 1 h later (p less than 0.005). However, after exercise bronchoconstriction, the histamine PC20 was 1.88 mg/ml (%SD, 2.03), not different from the control value (p less than 0.5). In contrast, the fall in FEV1 after exercise after prior inhalation of histamine was 15.63% (SD, 10.0%) compared with 23.13% (SD, 8.6%) on the control day (p less than 0.005). Therefore, inhibitory mediators released during histamine inhalation can cause exercise refractoriness; however, the converse is not true.

Background Without robust clinical evidence to guide titration of vasopressors in septic shock, it is unclear how dosing of these potent medications occurs. We sought to measure the proportion of vasopressor prescriptions for septic shock that were missing explicit targets and to describe the targets that we identified. Methods We conducted a multicentre, retrospective cohort study involving 9 intensive care units (ICUs) located at 3 academic hospitals in Canada and Australia. We reviewed charts of consecutive patients aged 18 years or older who were admitted to the ICU for a presumptive diagnosis of sepsis. Other inclusion criteria were hypotension (systolic arterial pressure ≤ 90 mm Hg or mean arterial pressure [MAP] ≤ 65 mm Hg) and continuous infusion of vasopressors for at least 1 hour within the initial 48 hours of ICU stay, the period of observation for this study. Results We included data from 369 patient charts. At least 1 target was specified in 99% of charts. The most common targets were MAP measurements (73%). The median initial MAP target was 65 (range 55-90) mm Hg. In multivariable regression models, hospital site and older age of the patient, but not comorbidities of the patient, were associated with MAP targets. In 40% of patients, the treating team modified the initial target at least once. Interpretation This study suggests that an explicit blood pressure target accompanies nearly every vasopressor prescription and that patient characteristics have little influence on its value. Identification of a titration strategy that will maximize benefit and minimize harm constitutes a research priority.

The objective of this pilot study was to assess the usability of the draft Ontario triage protocol, to estimate its potential impact on patient outcomes, and ability to increase resource availability based on a retrospective cohort of critically ill patients cared for during a non-pandemic period. Triage officers applied the protocol prospectively to 2 retrospective cohorts of patients admitted to 2 academic medical/surgical ICUs during an 8 week period of peak occupancy. Each patient was assigned a treatment priority (red -- 'highest', yellow -- 'intermediate', green -- 'discharge to ward', or blue/black -- 'expectant') by the triage officers at 3 separate time points (at the time of admission to the ICU, 48, and 120 hours post admission). Overall, triage officers were either confident or very confident in 68.4% of their scores; arbitration was required in 54.9% of cases. Application of the triage protocol would potentially decrease the number of required ventilator days by 49.3% (568 days) and decrease the total ICU days by 52.6% (895 days). On the triage protocol at ICU admission the survival rate in the red (93.7%) and yellow (62.5%) categories were significantly higher then that of the blue category (24.6%) with associated P values of < 0.0001 and 0.0003 respectively. Further, the survival rate of the red group was significantly higher than the overall survival rate of 70.9% observed in the cohort (P < 0.0001). At 48 and 120 hours, survival rates in the blue group increased but remained lower then the red or yellow groups. Refinement of the triage protocol and implementation is required prior to future study, including improved training of triage officers, and protocol modification to minimize the exclusion from critical care of patients who may in fact benefit. However, our results suggest that the triage protocol can help to direct resources to patients who are most likely to benefit, and help to decrease the demands on critical care resources, thereby making available more resources to treat other critically ill patients.