Prediction of successful veno-venous extracorporeal life support liberation using the oxygen challenge test.

BACKGROUND: The oxygen challenge test (OCT) is an underutilized measure of lung recovery, easily performed prior to proceeding with a trial-off V-V ECLS as part of a weaning algorithm. Evidence-based thresholds for OCT results which support continuing with V-V ECLS weaning are lacking, making interpretation of these tests challenging in clinical practice. METHODS: We performed a retrospective review of patients commenced on V-V ECLS as a bridge-to-recovery at Vancouver General Hospital from 2015-2019. The absolute PaO2 post-OCT and change in PaO2 proportional to incremental FiO2 change on the ventilator (∆PaO2 ) were evaluated as predictive screening metrics for identifying conditions favorable for successful trial-off of V-V ECLS. RESULTS: An optimal cut-off of PaO2 ≥ 240 mm Hg post-OCT (AUC 0.77) and ∆PaO2 ≥ 250 mm Hg (AUC 0.76) was identified as a threshold for predicting successful trials-off. A total of 26 and 24 patients achieved post-OCT PaO2 and ∆PaO2 thresholds, and 100% of these patients were liberated successfully from ECLS during their admission. CONCLUSIONS: The OCT can serve as an effective screen of shunt reduction and native lung recovery which can be used alongside other measures of ventilation to assess for suitability of liberation from V-V ECLS prior to a trial-off. Achieving a PaO2 ≥ 240 mm Hg post-OCT is a strong prognostic indicator for successful liberation from V-V ECLS during ICU admission.

Quality of life and functional status of patients treated with venovenous extracorporeal membrane oxygenation at 6 months.

PURPOSE: Quality of life (QoL) outcomes of patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) have been conflicting. This study reports on QoL outcomes for a broad group of ARDS patients managed with up-to-date treatment modalities. METHODS: We prospectively recruited patients at a quaternary hospital in the United Kingdom from 2013 to 2015 who were treated with ECMO for ARDS. We evaluated their pulmonary function and QoL at 6-months after admission using three QoL instruments: EuroQoL 5D (EQ-5), HADS, and PTSS-14. RESULTS: Forty-three patients included in the analysis had near-normal pulmonary function at 6 months. HADS showed moderate-to-severe anxiety and depression in 32% and 11% of patients, respectively. PTSS-14 showed 29% had signs of post-traumatic stress disorder. EQ-5D showed that 67% of patients had difficulty returning to usual activities, 74% suffered some pain, none reported severe problems and 77% were able to return to work. No clinical or demographic variables were associated with poor 6-month QoL. CONCLUSIONS: Patients with ARDS treated with ECMO generally had good QoL outcomes, similar to outcomes reported for patients managed without ECMO. With respect to QoL, VV-EMCO represents a valid treatment modality for patients with refractory ARDS.

Esophageal Balloon-Directed Ventilator Management for Postpneumonectomy Acute Respiratory Distress Syndrome.

OBJECTIVE: Postpneumonectomy patients may develop acute respiratory distress syndrome (ARDS). There is a paucity of data regarding the optimal management of mechanical ventilation for postpneumonectomy patients. Esophageal balloon pressure monitoring has been used in traditional ARDS patients to set positive end-expiratory pressure (PEEP) and minimize transpulmonary driving pressure (ΔP L), but its clinical use has not been previously described nor validated in postpneumonectomy patients. The primary objective of this report was to describe the potential clinical application of esophageal pressure monitoring to manage the postpneumonectomy patient with ARDS. DESIGN: Case report. Setting. Surgical intensive care unit (ICU) of a university-affiliated teaching hospital. Patient. A 28-year-old patient was involved in a motor vehicle collision, with a right main bronchus injury, that required a right-sided pneumonectomy to stabilize his condition. In the perioperative phase, they subsequently developed ventilator-associated pneumonia, significant cumulative positive fluid balance, and ARDS. Interventions. Prone positioning and neuromuscular blockade were initiated. An esophageal balloon was inserted to direct ventilator management. Measurements and Main Results. V T was kept around 3.6 mL/kg PBW, ΔP L at ≤14 cm H2O, and plateau pressure at ≤30 cm H2O. Lung compliance was measured to be 37 mL/cm H2O. PEEP was optimized to maintain end-inspiratory transpulmonary pressure (P L) < 15 cm H2O, and end-expiratory P L between 0 and 5 cm H2O. The maximal ΔP L was measured to be 11 cm H2O during the care of this patient. The patient improved with esophageal balloon-directed ventilator management and was eventually liberated from mechanical ventilation. CONCLUSIONS: The optimal targets for V T remain unknown in the postpneumonectomy patient. However, postpneumonectomy patients with ARDS may potentially benefit from very low V T and optimization of PEEP. We demonstrate the application of esophageal balloon pressure monitoring that clinicians could potentially use to limit injurious ventilation and improve outcomes in postpneumonectomy patients with ARDS. However, esophageal balloon pressure monitoring has not been extensively validated in this patient population.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. DESIGN: Multicenter prospective observational study. SETTING: ICU. PATIENTS: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). INTERVENTIONS: Daily measurement of serum inflammatory cytokines. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1ß on the day of diagnosis. CONCLUSIONS: The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-ß or tumor necrosis factor-α.

Vancouver General Hospital Pulmonary Embolism Response Team (VGH PERT): initial three-year experience.

PURPOSE: Clinical equipoise exists with the use of novel reperfusion therapies such as catheter-directed thrombolysis in the management of patients presenting to hospital with high risk pulmonary embolism (PE). Therapeutic options rely on clinical presentation, patient factors, physician preference, and institutional availability. We established a Pulmonary Embolism Response Team (PERT) to provide urgent assessment and multidisciplinary care for patients presenting to our institution with high-risk PE. METHODS: Data were retrospectively collected from PERT activations between January 2016 and December 2018. Chi square tests were used to determine differences in mortality across the three years of study. Logistic regression was used to evaluate 30- and 90-day mortality and occurrence of major bleeds between those receiving anticoagulation alone (AC) and those receiving advanced reperfusion therapy (ART). RESULTS: There were 128 PERT activations over three years, the majority originating from the emergency department. Eighty-five percent of activations were for submassive PE, with 56% of all activations assessed as submassive-high risk. Fifteen patients (12%) presented with massive PE. Advanced reperfusion therapy was used in 29 (23%) patients, of whom 25 (20%) received catheter-directed thrombolysis. There was an increased risk of major bleeding in the ART group compared with in the AC group (odds ratio [OR], 17.9; 95% confidence interval [CI], 4.1 to 125.0; P < 0.001), but no increased risk of mortality at 30 days (OR, 2.1; 95% CI, 0.4 to 9.1; P = 0.3). The 30-day mortality rate was 7.8%. CONCLUSION: We describe the first Canadian PERT, a multidisciplinary team aimed at providing urgent individualized care for patients with high-risk PE. Further research is necessary to determine whether a PERT improves clinical outcomes.

RéSUMé: OBJECTIF: Le concept d'équilibre clinique existe lors de l'utilisation de traitements innovants de reperfusion tels que la thrombolyse in situ (ou thrombolyse par cathéter) pour la prise en charge des patients se présentant à l'hôpital avec une embolie pulmonaire (EP) à haut risque. Les options thérapeutiques s'appuient sur la présentation clinique, les caractéristiques du patient, la préférence du médecin et la disponibilité institutionnelle. Nous avons mis sur pied une Équipe d'intervention en cas d'embolie pulmonaire (PERT - Pulmonary Embolism Response Team) afin de fournir une évaluation urgente et des soins multidisciplinaires aux patients se présentant dans notre institution avec une EP à haut risque. MéTHODE: Nous avons récolté rétrospectivement les données concernant les activations/alertes reçues par notre PERT entre janvier 2016 et décembre 2018. Des tests de chi carré ont été utilisés afin de déterminer les différences en matière de mortalité au cours des trois années de durée de l'étude. La régression logistique a été utilisée pour évaluer la mortalité à 30 et à 90 jours ainsi que la survenue de saignements majeurs entre les patients recevant uniquement un traitement anticoagulant (AC) et ceux recevant un traitement de reperfusion avancé (TRA). RéSULTATS: Il y a eu 128 alertes requérant l'activation de notre PERT en trois ans, la majorité provenant de l'urgence. Quatre-vingt-cinq pour cent des activations concernaient des EP submassives, et 56 % de toutes les activations ont été évaluées comme étant submassives à haut risque. Quinze patients (12 %) se sont présentés avec une EP massive. Un traitement de reperfusion avancé a été administré à 29 (23 %) patients, parmi lesquels 25 (20 %) ont reçu une thrombolyse in situ. Un risque accru de saignement majeur a été observé dans le groupe TRA par rapport au groupe AC (rapport de cotes [RC], 17,9; intervalle de confiance [IC] 95 %, 4,1 à 125,0; P < 0,001), mais il n'y avait pas de risque accru de mortalité à 30 jours (RC, 2,1; IC 95 %, 0,4 à 9,1; P = 0,3). Le taux de mortalité à 30 jours était de 7,8 %. CONCLUSION: Nous décrivons la première PERT canadienne, une équipe multidisciplinaire ayant pour but de prodiguer des soins personnalisés urgents aux patients avec embolie pulmonaire à haut risque. Des recherches supplémentaires sont nécessaires pour déterminer si une PERT améliore les pronostics cliniques.

Variation in the Management of Pain, Agitation, and Delirium in Intensive Care Units in British Columbia.

BACKGROUND: Pain, agitation, and delirium are associated with negative outcomes in critically ill patients. Reducing variation in pain, agitation, and delirium management among institutions could improve care. OBJECTIVES: To define opportunities to improve pain, agitation, and delirium management in intensive care units in British Columbia, Canada. METHODS: A 13-item survey was developed to determine practices for assessing and managing pain, agitation, and delirium. Target participants were persons designated as the most informed about pain, agitation, and delirium management at each of the 30 intensive care units in British Columbia. Main measures were protocol use, assessment tool(s) used and frequency, and management approaches. RESULTS: All 30 units responded; half of them had a unit-specific pain algorithm. The Behavioral Pain Scale and the numerical rating scale were the most common tools used to assess pain. Sites reported 15 different approaches to pain management: two-thirds used a sedation assessment tool, but some relied on physician diagnoses to identify sedation. Sites reported 18 different approaches to sedation management: most included an algorithm or order set for sedation management, but the most commonly used approach was individualized management by a clinician (17% for sedation and 30% for agitation). Sites reported 22 different approaches for delirium management: more than two-thirds used a delirium measurement instrument, but some relied on physician diagnoses to identify delirium. CONCLUSION: Variation in assessment and management of pain, agitation, and delirium in British Columbia intensive care units highlights opportunities to improve care.

Lactate and number of organ failures predict intensive care unit mortality in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Patients with acute-on-chronic liver failure (ACLF) have high mortality rates. Most prognostic scores were not developed for the intensive care unit (ICU) setting. We aimed to improve risk stratification for patients with ACLF in the ICU. METHODS: A training set with 240 patients with cirrhosis and organ failures (Chronic Liver Failure Sequential Organ Failure Assessment score [CLIF-SOFA]) from Curry Cabral Hospital (Portugal) and University of Alberta Hospital (Canada) in 2010-2016 was used to derive a prognostic model for ICU mortality. A validation set with 237 patients with cirrhosis and organ failures from Vancouver General Hospital (Canada) in 2000-2011 was used to evaluate its performance. RESULTS: Amongst patients in the training set, ICU and hospital mortality rates were 39.2% and 54.6% respectively. Median lactate (4.4 vs 2.5 mmol/L) and number of organ failures (3 vs 2) on admission to ICU were associated with higher likelihood of ICU mortality (P < 0.001 for both). The lactate and organ failures predictive model (LacOF) was derived to predict ICU mortality: -2.420 + 0.072 × lactate + 0.569 × number of organ failures (area under-the-curve [AUC], 0.76). In the validation set, the LacOF model discriminative ability (AUC, 0.85) outperformed the CLIF-SOFA (AUC, 0.79), Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure (AUC, 0.73), Model for End-stage Liver Disease score (AUC, 0.78) and Acute Physiology and Chronic Health Evaluation II scores (AUC, 0.74; P < 0.05 for all). The LacOF model calibration was good up to the 25% likelihood of ICU mortality. CONCLUSIONS: In patients with ACLF, lactate and number of organ failures on admission to ICU are useful to predict ICU mortality. This early prognostic evaluation may help to better stratify the risk of ICU mortality and thus optimize organ support strategies.

Dynamic Prognostication in Critically Ill Cirrhotic Patients With Multiorgan Failure in ICUs in Europe and North America: A Multicenter Analysis.

OBJECTIVES: To evaluate the Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score in acute on chronic liver failure patients admitted to ICUs from different global regions and compare discrimination ability with previously published scores. DESIGN: Retrospective pooled analysis. SETTING: Academic ICUs in Canada (Edmonton, Vancouver) and Europe (Paris, Barcelona, Chronic liver failure/Acute-on-Chronic Liver Failure in Cirrhosis [CANONIC] study). PATIENTS: Sample of analysis of 867 cirrhotic patients with acute on chronic liver failure admitted to ICU. Cumulative incidence functions of death were estimated by acute on chronic liver failure grade at admission and at day 3. Survival discrimination abilities of Chronic Liver Failure-Consortium Acute on Chronic Liver Failure, Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Child-Turcotte-Pugh scores were compared. INTERVENTIONS: ICU admission for organ support. MEASUREMENTS AND MAIN RESULTS: At admission 169 subjects (19%) had acute on chronic liver failure 1, 302 (35%) acute on chronic liver failure 2, and 396 (46%) had acute on chronic liver failure 3 with 90-mortality rates of 33%, 40%, and 74%, respectively (p < 0.001). At admission, Chronic Liver Failure-Consortium Acute on Chronic Liver Failure demonstrated superior discrimination at 90 days compared with Acute Physiology and Chronic Health Evaluation II (n = 532; concordance index 0.67 vs 0.62; p = 0.0027) and Child-Turcotte-Pugh (n = 666; 0.68 vs 0.64; p = 0.0035), but not Model for End-Stage Liver Disease (n = 845; 0.68 vs 0.67; p = 0.3). A Chronic Liver Failure-Consortium Acute on Chronic Liver Failure score greater than 70 at admission or on day 3 was associated with 90-day mortality rates of approximately 90%. Ninety-day mortality in grade 3 acute on chronic liver failure patients at admission who demonstrated improvement by day 3 was 40% (vs 79% in patients who did not). CONCLUSIONS: The Chronic Liver Failure-Consortium Acute on Chronic Liver Failure demonstrated better discrimination at day 28 and day 90 compared with Acute Physiology and Chronic Health Evaluation II and Child-Turcotte-Pugh. Patients who demonstrated clinical improvement post-ICU admission (e.g., acute on chronic liver failure 3 to 1 or 2) at day 3 had better outcomes than those who did not. In high-risk ICU patients (Chronic Liver Failure-Consortium Acute on Chronic Liver Failure > 70), decisions regarding transition to palliation should be explored between patient families and the ICU providers after a short trial of therapy.

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.

BACKGROUND: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury. METHODS: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America. Patients were between the ages of 18 and 80 years, had an American-European Consensus Criteria consensus diagnosis of ARDS, and had been mechanically ventilated for less than 72 h. In part A, open-label GSK2586881 was administered at doses from 0.1 mg/kg to 0.8 mg/kg to assess safety, pharmacokinetics, and pharmacodynamics. Following review of data from part A, a randomized, double-blind, placebo-controlled investigation of twice-daily doses of GSK2586881 (0.4 mg/kg) for 3 days was conducted (part B). Biomarkers, physiological assessments, and clinical endpoints were collected over the dosing period and during follow-up. RESULTS: Dose escalation in part A was well-tolerated without clinically significant hemodynamic changes. Part B was terminated after 39 of the planned 60 patients following a planned futility analysis. Angiotensin II levels decreased rapidly following infusion of GSK2586881, whereas angiotensin-(1-7) and angiotensin-(1-5) levels increased and remained elevated for 48 h. Surfactant protein D concentrations were increased, whereas there was a trend for a decrease in interleukin-6 concentrations in rhACE2-treated subjects compared with placebo. No significant differences were noted in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, oxygenation index, or Sequential Organ Failure Assessment score. CONCLUSIONS: GSK2586881 was well-tolerated in patients with ARDS, and the rapid modulation of RAS peptides suggests target engagement, although the study was not powered to detect changes in acute physiology or clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01597635 . Registered on 26 January 2012.

Prognostication of critically ill patients with acute-on-chronic liver failure using the Chronic Liver Failure-Sequential Organ Failure Assessment: A Canadian retrospective study.

PURPOSE: We evaluated the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score to predict survival in a Canadian critically ill cohort with acute-on-chronic liver failure. METHODS: We retrospectively examined 274 acute-on-chronic liver failure patients admitted to a quaternary level intensive care unit (ICU) between April 1, 2000, and April 30, 2011. We evaluated severity of illness scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) II, model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), SOFA, and CLIF-SOFA. RESULTS: On ICU admission, patients had the following median (interquartile range): APACHE II, 23 (19-28); MELD, 26 (19-35); CTP, 12 (10-13); SOFA, 15 (11-18); and CLIF-SOFA, 17 (13-21). In-hospital survival was 40%. There were no significant differences in survival for cirrhosis etiology, reason, or year of admission. The CLIF-SOFA score had the greatest area under receiver operating curve of 0.865 (95% confidence interval, 0.820-0.909) and outperformed the CTP, MELD, SOFA, and APACHE II scores. Sequential Organ Failure Assessment score performance improved on the third day of ICU admission (area under receiver operating curve, 0.935; 95% confidence interval, 0.895-0.975). CONCLUSIONS: The CLIF-SOFA and SOFA scores during the first 3 days of ICU admission appear to be highly predictive of in-hospital mortality.

Noninvasive ventilation practice patterns for acute respiratory failure in Canadian tertiary care centres: A descriptive analysis.

BACKGROUND: The extent of noninvasive ventilation (NIV) use for patients with acute respiratory failure in Canadian hospitals, indications for use and associated outcomes are unknown. OBJECTIVE: To describe NIV practice variation in the acute setting. METHODS: A prospective observational study involving 11 Canadian tertiary care centres was performed. Data regarding NIV indication, mode and outcomes were collected for all adults (>16 years of age) treated with NIV for acute respiratory failure during a four-week period (between February and August 2011). Logistic regression with site as a random effect was used to examine the association between preselected predictors and mortality or intubation. RESULTS: A total of 330 patients (mean [± SD] 30±12 per centre) were included. The most common indications for NIV initiation were pulmonary edema (104 [31.5%]) and chronic obstructive pulmonary disease (99 [30.0%]). Significant differences in indications for NIV use across sites, specialty of ordering physician and location of NIV initiation were noted. Although intubation rates were not statistically different among sites (range 10.3% to 45.4%), mortality varied significantly (range 6.7% to 54.5%; P=0.006). In multivariate analysis, the most significant independent predictor of avoiding intubation was do-not-resuscitate status (OR 0.11 [95% CI 0.03 to 0.37]). CONCLUSION: Significant variability existed in NIV use and associated outcomes among Canadian tertiary care centres. Assignment of do-not-resuscitate status prevented intubation.

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study.

INTRODUCTION: Critically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT. METHODS: We performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available. RESULTS: In the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001). CONCLUSIONS: SOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.

Hypoglycemia and risk of death in critically ill patients.

BACKGROUND: Whether hypoglycemia leads to death in critically ill patients is unclear. METHODS: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates. RESULTS: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P<0.001) and 2.10 (95% CI, 1.59 to 2.77; P<0.001), respectively. The association with death was increased among patients who had moderate hypoglycemia on more than 1 day (>1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001). CONCLUSIONS: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).

Intracranial pressure monitors in traumatic brain injury: a systematic review.

We conducted a systematic review to examine the relationship between intracranial pressure monitors (ICP) monitors and mortality in traumatic brain injury (TBI). We systematically searched for articles that met the following criteria: (1) adults patients, (2) TBI, (3) use of an ICP monitor, (4) point estimate for mortality with ICP monitoring (5) adjustment for potential confounders. Six observational studies were identified with 11,371 patients. There was marked between-study heterogeneity that precluded a pooled analysis. Patients with ICP monitors had different clinical characteristics and received more ICP targeted therapy in the ICU. Four studies found no significant relationship between ICP monitoring and survival, while the other two studies demonstrated conflicting results. Significant confounding by indication in observational studies limits the examination of isolated TBI interventions. More research should focus on interventions that affect TBI careplan systems. Further research is needed to identify which subset of severe TBI patients may benefit from ICP monitoring.

The impact of prolonged continuous wakefulness on resident clinical performance in the intensive care unit: a patient simulator study.

OBJECTIVE: To evaluate the impact of prolonged continuous wakefulness on resident performance under controlled experimental conditions. DESIGN: Experimental within-subjects comparison. SETTING: High-fidelity patient simulator. PARTICIPANTS: Twelve residents in an Internal Medicine Program at various stages of training (range, 1-35 mos). MEASUREMENTS: Performance was studied during 26 hrs of continuous wakefulness at four time points (8:00-10:00 am, 2:00-4:00 pm, 2:00-4:00 am, and 8:00-10:00 am the next day) using high-fidelity patient simulation. At each session, residents managed eight simulated dysrhythmias according to advanced cardiac life support protocols (advanced cardiac life support scenarios) and then managed a simulated critically ill patient (e.g., patient with meningitis) to test more complicated clinical decision-making (complex scenario). The frequency of previously defined major medical errors (i.e., action or inaction that likely would have resulted in significant harm in a real patient) was assessed by a scorer blinded to the time of the session. For each complex scenario, a global score between 0 and 100 was also given for overall performance. The impact of wakefulness on performance was assessed by using longitudinal mixed-effects models. RESULTS: For the complex scenarios, the mean number of errors increased from 0.92 +/- 0.90 in the first session to 1.58 +/- 0.79 in the fourth session (p = .09), and mean global score decreased from 56.8 +/- 14.6 to 49.6 +/- 12.6 (p = .02). For the advanced cardiac life support scenarios, the mean number of major errors committed in the advanced cardiac life support scenarios decreased during the study period (p = .01). However, essentially all of the improvement occurred between the first and second time points, suggesting that a substantial learning effect accounted for the findings. CONCLUSIONS: During prolonged continuous wakefulness of medical residents, clinical performance in the management of a simulated critically ill patient deteriorates. The practice of scheduling residents for extended work shifts (>24 hrs) should be reconsidered.

The efficacy and safety of glucose control algorithms in intensive care: a pilot study of the Survival Using Glucose Algorithm Regulation (SUGAR) trial.

INTRODUCTION: The benefits, harms and feasibility of intensive insulin therapy in critically ill patients remain unclear. Several single center studies have attempted to demonstrate the benefit of intensive insulin therapy in critically ill patients with variable results. OBJECTIVES: We conducted a pilot randomized trial to assess the feasibility, safety and clinical outcomes of preprinted glucose management algorithms before the initiation of a large multicenter trial. PATIENTS AND METHODS: Within 48 hours of admission to the intensive care unit, we randomized mechanically ventilated patients to either the "high" group (target serum glucose concentration 9-11 mmol/l) or the "low" group (target serum glucose concentration 5-7 mmol/l). To assess feasibility we measured the time to reach target glucose range, time in target range, morning glucose concentrations, average daily glucose concentrations, and number of crossovers. To assess safety, we measured the number of hypoglycemic events (serum glucose <2.2 mmol/l), and other serious adverse events such as cardiac arrests and seizures. RESULTS: Sixty-eight patients were enrolled (35 in the high group and 33 in the low group). During the first week, the median proportions of time spent in the target range were 35.7% and 53.0% for the high and low groups, respectlively (p = 0.0001). Morning glucose concentrations were 8.3 +/-1.6 mmol/l and 6.2 -/+1.2 mmol/l. One (2.9%) and 8 (24.2%) episodes of hypoglycemia (<2.2 mmol/l) occurred in the high and low groups, reflecting 0.002 and 0.03 hypoglycemic events per patient-day, respectlively. CONCLUSIONS: This pilot trial of intensive insulin therapy identified numerous challenges that helped in the preparation of an international multicenter randomized trial of intensive insulin therapy to evaluate benefits and harms.