Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Adding vitamin C to hydrocortisone lacks benefit in septic shock: a historical cohort study.

PURPOSE: Sepsis has high incidence and mortality rates, particularly in the intensive care unit (ICU). Corticosteroids may improve outcomes, and vitamin C may add benefit. We aimed to assess whether vitamin C and corticosteroids improved outcomes compared with corticosteroids alone. METHODS: This historical cohort study (11 December 2016 to 21 February 2018) was conducted in the ICU of a quaternary referral hospital. Patients with an ICU admission diagnosis of sepsis or septic shock who received vitamin C and hydrocortisone within 72 hr were compared with those who received only hydrocortisone. All patients received standard sepsis care including source control, antibiotics, and fluid resuscitation. Most patients received thiamine as standard ICU care. The primary outcome was hospital mortality. Secondary outcomes included ICU mortality, ventilator-free days, vasopressor-free days, dialysis use, and duration of ICU admission. RESULTS: One hundred and forty-four patients were included in the study. The mean (standard deviation [SD]) age was 64 (15) yr; 39% were female; and the mean (SD) Acute Physiology And Chronic Health Evaluation IV score was 89 (30). Eighty-eight patients did not receive vitamin C and 52 received vitamin C. There was no observed difference in hospital mortality between the non-vitamin C (36%) and vitamin C (39%) groups (adjusted odds ratio for hospital death, 0.52; 95% confidence interval, 0.20 to 1.34; P = 0.18). There were no statistically significant differences in any secondary outcomes. CONCLUSION: In this small observational study of ICU patients with septic shock, the addition of vitamin C to hydrocortisone therapy did significantly affect hospital mortality or other measures of mortality or organ dysfunction.

RéSUMé: OBJECTIF: Le sepsis comporte une incidence et des taux de mortalité élevés, particulièrement à l'unité de soins intensifs (USI). Les corticostéroïdes pourraient améliorer les pronostics, et la vitamine C pourrait être bénéfique. Notre objectif était d'évaluer si la vitamine C et les corticostéroïdes amélioraient les devenirs par rapport à un traitement de corticostéroïdes seulement. MéTHODE: Cette étude de cohorte historique (réalisée entre le 11 décembre 2016 et le 21 février 2018) a été réalisée à l'USI d'un hôpital quaternaire. Les patients ayant un diagnostic de sepsis ou de choc septique lors de leur admission à l'USI et ayant reçu de la vitamine C et de l'hydrocortisone dans les premières 72 heures ont été comparés à ceux n'ayant reçu que de l'hydrocortisone. Tous les patients ont reçu des soins standard pour le sepsis, soit un contrôle de la source de l'infection, un traitement antibiotique et une réanimation liquidienne. La plupart des patients ont reçu de la thiamine, un traitement standard à l'USI. Le critère d'évaluation principal était la mortalité hospitalière. Les critères d'évaluation secondaires comprenaient la mortalité à l'USI, les jours sans respirateur, les jours sans vasopresseurs, le recours à la dialyse et la durée de séjour à l'USI. RéSULTATS: Cent quarante-quatre patients ont été inclus dans notre étude. L'âge moyen (écart type [ÉT]) était de 64 (15) ans; 39 % étaient de sexe féminin; et le score APACHE IV moyen (ÉT) de 89 (30). Quatre-vingt-huit patients n'ont pas reçu de vitamine C et 52 en ont reçu. Aucune différence n'a été observée en matière de mortalité hospitalière entre les groupes sans vitamine C (36 %) ou avec vitamine C (39 %) (rapport de cotes ajusté pour la mortalité hospitalière, 0,52; intervalle de confiance 95 %, 0,20 à 1,34; P = 0,18). Il n'y a eu aucune différence statistiquement significative en ce qui touchait aux critères d'évaluation secondaires. CONCLUSION: Dans cette petite étude observationnelle portant sur des patients de l'USI en choc septique, l'ajout de vitamine C à un traitement d'hydrocortisone n'a pas eu d'impact significatif sur la mortalité hospitalière ou les autres mesures de mortalité ou d'atteintes organiques.

Association between intensive care unit occupancy at discharge, afterhours discharges, and clinical outcomes: a historical cohort study.

PURPOSE: There is a paucity of evidence evaluating whether intensive care unit (ICU) discharge occupancy is associated with clinical outcomes. It is unknown whether increased discharge occupancy leads to greater afterhours discharges and downstream consequences. We explore the association between ICU discharge occupancy and afterhours discharges, 72-hr readmission, and 30-day mortality. METHODS: This single-centre, historical cohort study included all patients discharged from the Vancouver General Hospital ICU between 5 April 2010 and 13 September 2017. Data were obtained from the British Columbia Critical Care Database. Occupancy was defined as the number of ICU bed hours utilized divided by the available bed hours for that day. Any discharge between 22:00 and 6:59 was considered afterhours. Logistic regression models adjusting for important covariates were constructed. RESULTS: We included 8,862 ICU discharges representing 7,288 individual patients. There were 1,180 (13.3%) afterhours discharges, 408 (4.6%) 72-hr readmissions, and 574 (6.5%) 30-day post-discharge deaths. Greater discharge occupancy was associated with afterhours discharges (per 10% increase: adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.03 to 1.20; P = 0.005). Discharge occupancy was not associated with 72-hr readmission (per 10% increase: aOR, 0.97; 95% CI, 0.87 to 1.09; P = 0.62) or 30-day mortality (per 10% increase: aOR, 1.05; 95% CI, 0.95 to 1.16; P = 0.32). Afterhours discharge was not associated with 72-hr readmission (aOR, 1.15; 95% CI, 0.86 to 1.54; P = 0.34) or 30-day mortality (aOR, 1.05; 95% CI, 0.82 to 1.36; P = 0.69). CONCLUSIONS: Greater ICU discharge occupancy was associated with a significant increase in afterhours discharges. Nevertheless, neither discharge occupancy nor afterhours discharge were associated with 72-hr readmission or 30-day mortality.

RéSUMé: OBJECTIF: Il n'existe que peu de données probantes évaluant si le taux d'occupation de l'unité de soins intensifs (USI) au moment du congé est associé aux devenirs cliniques. Nous ne savons pas si un taux d'occupation plus élevé au moment du congé entraîne davantage de congés pendant la nuit et si cette situation a des conséquences. Nous avons exploré l'association entre le taux d'occupation de l'USI au moment du congé et les congés donnés pendant la nuit, la réadmission dans les premières 72 h, et la mortalité à 30 jours. MéTHODE: Cette étude de cohorte historique et monocentrique a englobé tous les patients ayant reçu leur congé de l'USI de l'Hôpital général de Vancouver entre le 5 avril 2010 et le 13 septembre 2017. Les données ont été tirées de la Base de données des soins intensifs de Colombie-Britannique (British Columbia Critical Care Database). Le taux d'occupation était défini comme le nombre d'heures d'occupation de lit de l'USI utilisées divisé par le nombre d'heures d'occupation de lit disponibles pour ladite journée. Tout congé reçu entre 22 h et 6 h 59 était considéré comme survenant pendant la nuit. Des modèles de régression logistique ont été élaborés afin de tenir compte des covariables importantes. RéSULTATS: Nous avons inclus 8862 congés de l'USI, représentant 7288 patients individuels. Au total, il y a eu 1180 (13,3 %) congés donnés pendant la nuit, 408 (4,6 %) réadmissions dans les 72 h suivantes, et 574 (6,5 %) décès à 30 jours après le congé. Un taux d'occupation plus élevé au moment du congé était associé à des congés pendant la nuit (par augmentation de 10 % : rapport de cotes ajusté [RCA], 1,12; intervalle de confiance [IC] 95 %, 1,03 à 1,20; P = 0,005). Le taux d'occupation lors du congé n'a pas été associé à une réadmission dans les premières 72 h (par augmentation de 10 % : RCA, 0,97; IC 95 %, 0,87 à 1,09; P = 0,62) ou à une mortalité à 30 jours (par augmentation de 10 % : RCA, 1,05; IC 95 %, 0,95 à 1,16; P = 0,32). Les congés pendant la nuit n'ont pas été associés à une réadmission dans les 72 h suivantes (RCA, 1,15; IC 95 %, 0,86 à 1,54; P = 0,34) ou à une mortalité à 30 jours (RCA, 1,05; IC 95 %, 0,82 à 1,36; P = 0,69). CONCLUSION: Un taux d'occupation de l'USI plus élevé au moment du congé était associé à une augmentation significative des congés donnés pendant la nuit. Cependant, ni le taux d'occupation lors du congé, ni le congé donné pendant la nuit, n'étaient associés à une réadmission à 72 h ou une mortalité à 30 jours.

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.

Association of intensive care unit occupancy during admission and inpatient mortality: a retrospective cohort study.

PURPOSE: There is conflicting evidence regarding the influence of intensive care unit (ICU) occupancy at the time of admission on important patient outcomes such as mortality. The objective of this analysis was to characterize the association between ICU occupancy at the time of ICU admission and subsequent mortality. METHODS: This single-centre, retrospective cohort study included all patients admitted to the ICU at the Vancouver General Hospital between 4 January 2010 and 8 October 2017. Intensive care unit occupancy was defined as the number of ICU bed hours utilized in a day divided by the total amount of ICU bed hours available for that day. We constructed mixed-effects logistic regression models controlling for relevant covariates to assess the impact of admission occupancy quintiles on total inpatient (ICU and ward) and early (72-hr) ICU mortality. RESULTS: This analysis included 10,365 ICU admissions by 8,562 unique patients. Compared with ICU admissions in the median occupancy quintile, admissions in the highest and second highest occupancy quintile were associated with a significant increase in the odds of inpatient mortality (highest: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.12 to 1.59; P value < 0.001; second highest: OR, 1.21; 95% CI, 1.02 to 1.44; P value < 0.03). No association between admission occupancy and 72-hr ICU mortality was observed. CONCLUSIONS: Admission to the ICU on days of high occupancy was associated with increased inpatient mortality, but not with increased 72-hr ICU mortality. Capacity strain on the ICU may result in significant negative consequences for patients, but further research is needed to fully characterize the complex effects of capacity strain.

Outcomes of Critically Ill Patients Who Have Serotype 5 Invasive Pneumococcal Disease.

PURPOSE: To determine whether invasive pneumococcal disease (IPD) due to serotype 5, which occurred as a local outbreak in 2006 to 2007, is associated with intensive care unit (ICU) admission, hospital mortality, or organ supports in those who are critically ill. MATERIALS AND METHODS: Retrospective review of patients who presented with IPD to 2 tertiary hospitals in Vancouver, Canada, from July 2004 to June 2007. We compared patient characteristics, interventions, and outcomes between patients who had serotype 5 and other serotypes using bivariate and multivariate analyses. RESULTS: A total of 149 patients had serotype 5 and 106 had nonserotype 5. Patients with serotype 5 were younger, had lower prevalence of comorbid diseases, and had higher rates of substance use than patients with nonserotype 5. There were no differences in chest tube placement for complications of pneumonia or in ICU admission. Frequency of necrotizing pneumonia and hospital mortality were lower in the serotype 5 group. For the 71 patients with IPD who were admitted to ICU, there was no difference in severity of illness, ICU length of stay, or ICU mortality between the groups. There was also no difference in organ supports except that the serotype 5 group was more likely to receive vasopressors. CONCLUSION: Serotype 5 in patients who have IPD is associated with no difference in ICU admission but with increased use of vasopressors and lower hospital mortality.

Compassionate End-of-Life Care: Mixed-Methods Multisite Evaluation of the 3 Wishes Project.

Background: The 3 Wishes Project (3WP) is an end-of-life program that aims to honor the dignity of dying patients by creating meaningful patient- and family-centered memories while promoting humanistic interprofessional care. Objective: To determine whether this palliative intervention could be successfully implemented-defined as demonstrating value, transferability, affordability, and sustainability-beyond the intensive care unit in which it was created. Design: Mixed-methods formative program evaluation. (ClinicalTrials.gov: NCT04147169). Setting: 4 North American intensive care units. Participants: Dying patients, their families, clinicians, hospital managers, and administrators. Intervention: Wishes from dying patients, family members, and clinicians were elicited and implemented. Measurements: Patient characteristics and processes of care; the number, type, and cost of each wish; and semistructured interviews and focus groups with family members, clinicians, and managers. Results: A total of 730 patients were enrolled, and 3407 wishes were elicited. Qualitative data were gathered from 75 family members, 72 clinicians, and 20 managers or hospital administrators. Value included intentional comforting of families as they honored the lives and legacies of their loved ones while inspiring compassionate clinical care. Factors promoting transferability included family appreciation and a collaborative intensive care unit culture committed to dignity-conserving end-of-life care. Staff participation evolved from passive support to professional agency. Program initiation required minimal investment for reusable materials; thereafter, the mean cost was $5.19 (SD, $17.14) per wish. Sustainability was demonstrated by the continuation of 3WP at each site after study completion. Limitation: This descriptive formative evaluation describes tertiary care center-specific experiences rather than aiming for generalizability to all jurisdictions. Conclusion: The 3WP is a transferrable, affordable, and sustainable program that provides value to dying patients, their families, clinicians, and institutions. Primary Funding Source: Greenwall Foundation.

Moral distress in intensive care unit personnel is not consistently associated with adverse medication events and other adverse events.

PURPOSE: To examine the association between moral distress in ICU personnel, and medication errors and adverse events, and other adverse events. MATERIALS AND METHODS: In 13 ICUs, we measured moral distress once in all ICU staff, and incidence of five explicity-defined adverse safety events over 2 years. In 10 of the ICUs, pharmacists tabulated medication errors and adverse events during 1 day in the 2-year period. Average moral distress scores for each professional group were correlated with each safety measure. RESULTS: In the pharmacy study, there were almost no significant correlations between moral distress and measures of medication safety. However, higher moral distress in nurses was associated with more interceptions of near misses per administration error (r = 0.68, p = 0.04), and higher moral distress in physicians was associated with more incorrect measurements for medication monitoring per recommended action for monitoring (r = 0.68, p = 0.03). For the other adverse events, the only significant association was a positive association between moral distress in physicians and bleeding while on anticoagulants (OR: 1.1; 95% CI: 1.0-1.3). CONCLUSION: Moral distress in ICU personnel is generally not associated with medication errors or adverse events, or other adverse events, but it may be associated with both hyper-vigilance and distraction.

Development of a Provincial initiative to improve glucose control in critically ill patients.

OBJECTIVE: To describe the development, implementation and initial evaluation of an initiative to improve glucose control in critically ill patients. DESIGN: Glucose control in critically ill patients was chosen by critical care leaders as a target for improvement. This was an observational study to document changes in processes and measures of glucose control in each intensive care unit (ICU). ICU nurse educators were interviewed to document relevant changes between April 2012 and April 2016. SETTING: 16 ICUs in British Columbia, Canada. PARTICIPANTS: ICU leaders. INTERVENTION(S): A community of practice (CoP) was formed, guidelines were adopted, two learning sessions were held, and an electronic system to collect data was created. Then, each ICU introduced their own educational and process interventions. MAIN OUTCOME MEASURE(S): Average hyperglycemic index (area under the curve of serum glucose concentration versus time above the upper limit (10 mmol/l) divided by time on insulin infusion), number of hypoglycemic events (<3.5 mmol/l) divided by time on insulin infusion and standardized mortality rate (actual/predicted hospital mortality) for each 3-month period. RESULTS: Although there were some isolated points and short trends that indicated special cause variation, there were no major trends over time and no obvious association with any of the process changes for each hospital. However, the average hyperglycemic index was higher in some of the smaller hospitals than in the larger hospitals. CONCLUSIONS: In this, 4-year observation of glucose control in ICUs within a CoP, the lack of sustained improvement suggests the need for more active and durable interventions.

Implementation of Neurocritical Care Is Associated With Improved Outcomes in Traumatic Brain Injury.

Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients. METHODS: We conducted a single-center quasi-experimental uncontrolled pre- and post-NCC study in severe traumatic brain injury patients (Glasgow Coma Scale ≤8). The NCC program includes consultation with a neurointensivist and neurosurgeon and multimodal neuromonitoring. Demographic, injury severity metrics, neurophysiologic data, and therapeutic interventions were collected. Glasgow Outcome Scale (GOS) at 6 months was the primary outcome. Multivariable ordinal logistic regression was used to model the association between NCC implementation and GOS at 6 months. RESULTS: A total of 113 patients were identified: 76 pre-NCC and 37 post-NCC. Mean age was 39 years (standard deviation [SD], 2) and 87 of 113 (77%) patients were male. Median admission motor score was 3 (interquartile ratio, 1-4). Daily mean arterial pressure was higher (95 mmHg [SD, 10]) versus (88 mmHg [SD, 10], p<0.001) and daily mean core body temperature was lower (36.6°C [SD, 0.90]) versus (37.2°C [SD, 1.0], p=0.001) post-NCC compared with pre-NCC, respectively. Multivariable regression modelling revealed the NCC program was associated with a 2.5 increased odds (odds ratios, 2.5; 95% confidence interval, 1.1-5.3; p=0.022) of improved 6-month GOS. CONCLUSIONS: Implementation of a NCC program is associated with improved 6 month GOS in severe TBI patients.

Novel Therapies for Myocardial Irritability following Extreme Hydroxychloroquine Toxicity.

Introduction. Hydroxychloroquine (HCQ) overdose is rare and potentially deadly when consumed in large doses. Management of severe HCQ toxicity is limited and infrequently reported. This report presents the case of a massive ingestion of HCQ. Case Report. A 23-year-old female presents following an intentional ingestion of approximately 40 g of HCQ. Within six hours after ingestion, she developed severe hemodynamic instability resulting from myocardial irritability with frequent ventricular ectopic activity leading to runs of polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) requiring multiple defibrillations. Additional treatments included intravenous diazepam, epinephrine, norepinephrine, sodium bicarbonate, and magnesium sulfate. Despite the ongoing hemodynamic instability, the patient was also treated with Intralipid (ILE) and received hemodialysis. Improvements in her hemodynamics were observed after 18 hours. She survived her massive overdose of HCQ. Conclusion. HCQ poisoning is rare but serious because of its rapid progression to life-threatening symptoms. Hemodynamic support, gastric decontamination, electrolyte monitoring and replacement, and management of arrhythmias are the mainstays of treatment. The combined role of dialysis and ILE in the setting of massive HCQ overdose may improve outcomes.

Intensive versus conventional glucose control in critically ill patients with traumatic brain injury: long-term follow-up of a subgroup of patients from the NICE-SUGAR study.

PURPOSE: To compare the effect of intensive versus conventional blood glucose control in patients with traumatic brain injury. METHODS: In a large international randomized trial patients were randomly assigned to a target blood glucose (BG) range of either 4.5-6.0 mmol/L (intensive control) or <10 mmol/L (conventional control). Patients with traumatic brain injury (TBI) were identified at randomization and data were collected to examine the extended Glasgow outcome score (includes mortality) at 24 months. RESULTS: Of the 6104 randomized patients, 391 satisfied diagnostic criteria for TBI; 203 (51.9%) were assigned to intensive and 188 (48.1%) to conventional control; the primary outcome was available for 166 (81.8%) and 149 (79.3%) patients, respectively. The two groups had similar baseline characteristics. At 2 years 98 (58.7%) patients in the intensive group and 79 (53.0%) in the conventional group had a favorable neurological outcome (odds ratio [OR] 1.26, 95% CI 0.81-1.97; P = 0.3); 35 patients (20.9%) in the intensive group and 34 (22.8%) in the conventional group had died (OR 0.90, 95% CI 0.53-1.53; P = 0.7); moderate hypoglycemia (BG 2.3-3.9 mmol/L; 41-70 mg/dL) occurred in 160/202 (79.2%) and 17/188 (9.0%), respectively (OR 38.3, 95% CI 21.0-70.1; P < 0.0001); severe hypoglycemia (BG ≤ 2.2 mmol/L; ≤40 mg/dL) in 10 (4.9%) and 0 (0.0%), respectively (OR 20.5 95% CI 1.2-351.6, P = 0.003). CONCLUSION: Although patients with traumatic brain injury randomly assigned to intensive compared to conventional glucose control experienced moderate and severe hypoglycemia more frequently, we found no significant difference in clinically important outcomes.

Extracorporeal membrane oxygenation after protracted ventricular fibrillation cardiac arrest: case report and discussion.

Extracorporeal membrane oxygenation (ECMO) is a method to provide temporary cardiac and respiratory support to critically ill patients. In recent years, the role of ECMO in emergency departments (EDs) for select adults has increased. We present the dramatic case of a 29-year-old man who was placed on venoarterial ECMO for cardiogenic shock and respiratory failure following collapse and protracted ventricular fibrillation cardiac arrest in our ED. Resuscitation efforts prior to ECMO commencement included 49 minutes of virtually continuous cardiopulmonary resuscitation (CPR), 11 defibrillations, administration of numerous medications, including a thrombolytic agent, while CPR was ongoing, percutaneous coronary intervention and stenting for a mid-left anterior descending coronary artery dissection and thrombotic occlusion, inotropic support, and intra-aortic balloon pump counterpulsation. Over the next 48 hours following ECMO commencement, the patient's cardiorespiratory function rapidly improved, and he was discharged home 9 days after admission with no neurologic sequelae. The history, indications, and increasing role of ECMO in a range of conditions, including cardiac arrest, are reviewed.

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.

Intensity of continuous renal replacement therapy in acute kidney injury in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Acute kidney injury is a common finding among patients in the intensive care unit (ICU) and is an independent predictor of mortality. The optimal intensity and timing of continuous renal replacement therapy (CRRT), in critically ill patients remain unclear. The purpose of this study was to conduct a systematic review and meta-analysis of all prospective randomized controlled trials (RCTs) to determine the effect of intensity of CRRT on the survival of patients with acute renal failure (ARF) in ICU setting. METHODS: Search strategy and data source. Electronic databases were searched on MEDLINE (through February 2010), ISIWeb of Science, and Cochrane Central Register of Controlled Trials (2010); Pub Med ''Related articles.'' Trial authors were also contacted for additional information. Study selection and data abstraction. All prospective clinical trials comparing the intensity of CRRT in adult patients with ARF and with explicit reporting of mortality were included. Three authors independently evaluated articles for eligibility and extracted data on study quality and outcomes. Meta-analysis used a random-effects model. RESULT: Of the 322 citations, 5 trials (n = 2402) were included in the meta-analysis, which met all the inclusion and exclusion criteria. Meta-analysis showed that in critically ill patients with acute kidney injury, the high-dose CRRT did not reduce mortality at 28 days. (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.70-1.11; P = 0.28). CONCLUSION: In critically ill patients with acute kidney injury, the high-dose CRRT did not reduce mortality at 28 days.

The safety of synthetic colloid in critically ill patients with severe traumatic brain injuries.

PURPOSE: Although 4% albumin is associated with increased mortality in patients with traumatic brain injury (TBI), evidence concerning the safety of synthetic colloids is lacking. We aimed to determine if there is an association between synthetic colloids and mortality in patients with severe TBI. MATERIALS AND METHODS: A retrospective cohort study of patients with severe TBI was conducted. Data were collected on all intravenous fluids administered during the first 14 days of admission. Multivariable Cox proportional hazards regression was used to model the association between daily cumulative pentastarch quintiles and mortality. RESULTS: Patients receiving pentastarch had higher Acute Physiology and Chronic Health II scores (23.9 vs 21.6, P < .01), frequency of craniotomy (42.5% vs 21.6%, P = .02), longer duration of intensive care unit stay (12 vs 4 days, P < .01), and mechanical ventilation (10 vs 3 days, P < .01). On unadjusted Cox regression, patients in the highest quintile of cumulative pentastarch administration had a higher rate of mortality compared with those receiving no colloid (hazard ratio, 3.8; 95% confidence interval, 1.2-12.4; P = .03). However, this relationship did not persist in the final multivariable model (hazard ratio 1.0; 95% confidence interval, 0.25-4.1; P = .98). CONCLUSION: There was no association between cumulative exposure to pentastarch and mortality in patients with severe TBI.

A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations.

OBJECTIVE: Clinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations. METHODS: MEDLINE (1966-February 2008), EMBASE (1980-February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0-100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality. RESULTS: Twenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62-76%)], scope/purpose [62% (95% CI 55-68%)], rigor of development [51% (95% CI 42-60%)], editorial independence [39% (95% CI 26-52%)], stakeholder involvement [32% (95% CI 26-37%)] and applicability [19% (95% CI 12-26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations. CONCLUSION: Variation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.