Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit.

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Optic Nerve Sheath Diameter Ultrasound for Raised Intracranial Pressure: A Literature Review and Meta-analysis of its Diagnostic Accuracy.

Optic nerve sheath diameter (ONSD) ultrasound is becoming increasingly more popular for estimating raised intracranial pressure (ICP). We performed a systematic review and analysis of the diagnostic accuracy of ONSD when compared to the standard invasive ICP measurement. METHOD: We performed a systematic search of PUBMED and EMBASE for studies including adult patients with suspected elevated ICP and comparing sonographic ONSD measurement to a standard invasive method. Quality of studies was assessed using the QUADAS-2 tool by two independent authors. We used a bivariate model of random effects to summarize pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Heterogeneity was investigated by meta-regression and sub-group analyses. RESULTS: We included 18 prospective studies (16 studies including 619 patients for primary outcome). Only one study was of low quality, and there was no apparent publication bias. Pooled sensitivity was 0.9 [95% confidence intervals (CI): 0.85-0.94], specificity was 0.85 (95% CI: 0.8-0.89), and DOR was 46.7 (95% CI: 26.2-83.2) with partial evidence of heterogeneity. The Area-Under-the-Curve of the summary Receiver-Operator-Curve was 0.93 (95% CI: 0.91-0.95, P < .05). No covariates were significant in the meta-regression. Subgroup analysis of severe traumatic brain injury and parenchymal ICP found no heterogeneity. ICP and ONSD had a correlation coefficient of 0.7 (95% CI: 0.63-0.76, P < .05). CONCLUSION: ONSD is a useful adjunct in ICP evaluation but is currently not a replacement for invasive methods where they are feasible.

Residual Lung Injury in Patients Recovering From COVID-19 Critical Illness: A Prospective Longitudinal Point-of-Care Lung Ultrasound Study.

Scarce data exist regarding the natural history of lung lesions detected on ultrasound in those who survive severe COVID-19 pneumonia. OBJECTIVE: We performed a prospective analysis of point-of-care ultrasound (POCUS) findings in critically ill COVID-19 patients during and after hospitalization. METHODS: We enrolled 171 COVID-19 intensive care unit patients. POCUS of the lungs was performed with phased array (2-4 MHz), convex (2-6 MHz) and linear (10-15 MHz) transducers, scanning 12 lung areas. Chest computed tomography angiography was performed to exclude suspected pulmonary embolism. Survivors were clinically and sonographically evaluated during a 4 month period for evidence of residual lung injury. Chest computed tomography angiography and echocardiography were used to exclude pulmonary hypertension (PH) and chest high-resolution-computed-tomography to exclude interstitial lung disease (ILD) in symptomatic survivors. RESULTS: Cox regression analysis showed that lymphocytopenia (hazard ratio [HR]: 0.88, 95% confidence intervals [CI]: 0.68-0.96, p = .048), increased lactate (HR: 1.17, 95% CI: 0.94-1.46, p = 0.049), and D-dimers (HR: 1.21, 95% CI: 1.03-1.44, p = .03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < .05). During follow-up, POCUS with clinical and laboratory parameters integrated in the semi-quantitative Riyadh-Residual-Lung-Injury scale had sensitivity of 0.82 (95% CI: 0.76-0.89) and specificity of 0.91 (95% CI: 0.94-0.95) in predicting ILD. The prevalence of PH and ILD (non-specific-interstitial-pneumonia) was 7% and 11.8%, respectively. CONCLUSION: POCUS showed ability to monitor the evolution of severe COVID-19 pneumonia after hospital discharge, supporting its integration in clinical predictive models of residual lung injury.

Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report.

BACKGROUND: Fulminant (life-threatening) COVID-19 can be associated with acute respiratory failure (ARF), multi-system organ failure and cytokine release syndrome (CRS). We present a rare case of fulminant COVID-19 associated with reverse-takotsubo-cardiomyopathy (RTCC) that improved with therapeutic plasma exchange (TPE). CASE PRESENTATION: A 40 year old previous healthy male presented in the emergency room with 4 days of dry cough, chest pain, myalgias and fatigue. He progressed to ARF requiring high-flow-nasal-cannula (flow: 60 L/minute, fraction of inspired oxygen: 40%). Real-Time-Polymerase-Chain-Reaction (RT-PCR) assay confirmed COVID-19 and chest X-ray showed interstitial infiltrates. Biochemistry suggested CRS: increased C-reactive protein, lactate dehydrogenase, ferritin and interleukin-6. Renal function was normal but lactate levels were elevated. Electrocardiogram demonstrated non-specific changes and troponin-I levels were slightly elevated. Echocardiography revealed left ventricular (LV) basal and midventricular akinesia with apex sparing (LV ejection fraction: 30%) and depressed cardiac output (2.8 L/min) consistent with a rare variant of stress-related cardiomyopathy: RTCC. His ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen was < 120. He was admitted to the intensive care unit (ICU) for mechanical ventilation and vasopressors, plus antivirals (lopinavir/ritonavir), and prophylactic anticoagulation. Infusion of milrinone failed to improve his cardiogenic shock (day-1). Thus, rescue TPE was performed using the Spectra Optia™ Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA) without protective antibodies. Over 5 days he received daily TPE (each lasting 4 hours). His lactate levels, oxygenation, and LV function normalized and he was weaned off vasopressors. His inflammation markers improved, and he was extubated on day-7. RT-PCR was negative on day-17. He was discharged to home isolation in good condition. CONCLUSION: Stress-cardiomyopathy may complicate the course of fulminant COVID-19 with associated CRS. If inotropic therapy fails, TPE without protective antibodies may help rescue the critically ill patient.

Sepsis in Traumatic Brain Injury: Epidemiology and Outcomes.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. Risk factors for in-hospital mortality include older age, co-morbidity, and TBI severity. Few studies have investigated the role of sepsis in individuals with TBI. METHODS: We studied adult patients with TBI admitted to intensive care over a 5-year period. Patient characteristics were identified by linking clinical and administrative databases. Charts of individuals with TBI and sepsis were manually reviewed. Predictors of ICU and hospital mortality were identified using logistic regression modeling. RESULTS: Four hundred eighty-six individuals with TBI were admitted to intensive care. Sixteen (3.3%) developed sepsis. Pneumonia was the most common source (94%). Staphylococcus aureus was the most common pathogen (75%). ICU lengths of stay (LOS) (12.2 days [interquartile range (IQR) 4.4-23.5] versus 3.7 days [IQR 1.7-8.2]; p < 0.001) and hospital LOS (28.0 days [IQR 11.8-41.4] versus 15.3 days [IQR 5.0-30.9]; p = 0.017) were longer in patients with TBI and sepsis. Sepsis was not associated with ICU (adjusted odds ratio [aOR] 0.51; 95%CI 0.12-2.27; p = 0.38) or hospital (aOR 0.78; 95% CI 0.21-2.96; p = 0.78) mortality, though age (aOR 1.02; 95% CI 1.00-1.04; p = 0.014 for hospital mortality), severe TBI (aOR 3.71; 95% CI 1.52-9.08; p = 0.004 for ICU mortality and 4.10; 95% CI 1.95-8.65; p < 0.001 for hospital mortality), and APACHE II score (aOR 1.19; 95% CI 1.11-1.28; p < 0.001 for ICU mortality and 1.22; 95% CI 1.14-1.31; p < 0.001 for hospital mortality) were. CONCLUSION: Sepsis in patients with TBI was not associated with mortality; however, sepsis was associated with increased health care utilization (ICU and hospital LOS).

Donation after circulatory determination of death in western Canada: a multicentre study of donor characteristics and critical care practices.

PURPOSE: Donation after circulatory determination of death (DCD) has been performed in Canada since 2006. Numerous aspects of donor management remain controversial. METHODS: We performed a multicentre cohort study involving potential DCD donors in western Canada (2008-2017), as well as recipients of their organs, to describe donor characteristics and critical care practices, and their relation to one-year recipient and graft survival. RESULTS: There were 257 patients in four provinces that underwent withdrawal of life-sustaining therapies (WLST) in anticipation of possible DCD. The proportion of patients that died within two hours of WLST ranged from 67% to 88% across provinces (P = 0.06), and was predicted by deeper coma (P = 0.01), loss of pupillary light or corneal reflexes (P = 0.02), and vasopressor use (P = 0.01). There were significant differences between provinces in time intervals from onset of hypotension to death (9-11 min; P = 0.02) and death to vascular cannulation (7-10 min; P < 0.001). There was inconsistency in pre-mortem heparin administration (82-96%; P = 0.03), including timing (before vs after WLST; P < 0.001) and dose (≥ 300 vs < 300 units·kg-1; P < 0.001). Donation after circulatory death provided organs for 321 kidney, 81 liver, and 50 lung transplants. One-year recipient and graft survival did not differ among provinces (range 85-90%, P = 0.45). Predictors of death or graft failure included older recipient age (odds ratio [OR] per year, 1.04; 95% confidence interval [CI],1.01 to 1.07) and male donor sex (OR, 3.35; 95% CI, 1.39 to 8.09), but not time intervals between WLST and cannulation or practices related to heparin use. CONCLUSION: There is significant variability in critical care DCD practices in western Canada, but this has not resulted in significant differences in recipient or graft survival. Further research is required to guide optimal management of potential DCD donors.

RéSUMé: OBJECTIF: Le don d'organes après décès cardiocirculatoire (DDC) est pratiqué au Canada depuis 2006. De nombreux aspects touchant à la prise en charge des donneurs demeurent controversés. MéTHODE: Nous avons réalisé une étude de cohorte multicentrique auprès de donneurs potentiels de DDC dans l'Ouest canadien (2008­2017), ainsi qu'auprès des récipiendaires de leurs organes, afin de décrire les caractéristiques des donneurs et les pratiques de soins intensifs, ainsi que la relation entre ces éléments et la survie à un an des récipiendaires et des organes greffés. RéSULTATS: Au total, 257 patients provenant de quatre provinces ont subi une interruption des traitements de survie en vue d'un possible DDC. La proportion de patients décédés dans les deux heures suivant l'interruption des traitements de survie allait de 67 % à 88 % dans toutes les provinces à l'étude (P = 0,06) et pouvait être prédite par une profondeur du coma plus importante (P = 0,01), la perte de la réaction pupillaire à la lumière ou des réflexes cornéens (P = 0,02), et l'utilisation de vasopresseurs (P = 0,01). Des différences significatives ont été observées entre les différentes provinces dans les intervalles de temps entre le début de l'hypotension et le décès (9­11 min; P = 0,02) et entre le décès et la canulation vasculaire (7­10 min; P < 0,001). Il y avait divergence dans l'administration d'héparine avant le décès (82-96 %; P = 0,03), notamment en ce qui concerne le moment d'administration (avant vs après l'interruption des traitements de survie; P < 0,001) et la posologie (≥ 300 vs < 300 unités·kg−1; P < 0,001). Le don après décès cardiocirculatoire a permis de procurer des organes pour 321 greffes rénales, 81 greffes hépatiques et 50 greffes pulmonaires. La survie à un an du récipiendaire et du greffon ne différait pas d'une province à l'autre (allant de 85 à 90 %, P = 0,45). Les prédicteurs de décès ou de la défaillance du greffon incluaient l'âge plus avancé du récipiendaire (rapport de cotes [RC] par année, 1,04; intervalle de confiance [IC] 95 %, 1,01 à 1,07) et un donneur de sexe masculin (RC, 3,35; IC 95 %, 1,39 à 8,09), mais pas les intervalles de temps entre l'interruption des traitements de survie et la canulation, ni les pratiques liées à l'utilisation d'héparine. CONCLUSION: Il existe une importante variabilité dans les pratiques de soins intensifs pour le DDC dans l'Ouest canadien, mais cette variabilité n'a pas résulté en différences significatives en matière de survie des récipiendaires ou des greffons. Des recherches supplémentaires sont nécessaires afin d'aiguiller la prise en charge optimale des donneurs potentiels de DDC.

The impact of cirrhosis in patients undergoing cardiac surgery: a retrospective observational cohort study.

PURPOSE: Patients with cirrhosis and concomitant coronary/valvular heart disease present a clinical dilemma. The therapeutic outcome of major cardiac surgery is significantly poorer in patients with cirrhosis compared with patients without cirrhosis. To address this, we aimed to identify associations between the severity of cirrhosis and post-cardiac surgical outcomes. METHODS: A historical cohort analysis of patients undergoing cardiac surgery at the University of Alberta Hospital from January 2004 to December 2014 was used to identify and propensity score-match 60 patients with cirrhosis to 310 patients without cirrhosis. The relationships between cirrhosis and i) mortality, ii) postoperative complications, and iii) requirement of healthcare resources were evaluated. RESULTS: Ten-year mortality was significantly higher in cirrhotic patients compared with propensity score-matched non-cirrhotic patients (40% vs 20%; relative risk [RR], 2.0; 95% confidence interval [CI], 1.3 to 2.9; P = 0.001). Cirrhotic patients had more complications (63% vs 48%; RR, 1.3; 95% CI, 1.05 to 1.7; P = 0.02), longer median [interquartile range (IQR)] intensive care unit stays (5 [3-11] vs 2 [1-4] days; P < 0.001), time on mechanical ventilation (median [IQR] 2 [1-5] vs 1 [0.5-1.2] days; P < 0.001) and more frequently required renal replacement therapy (15% vs 6%; RR, 2.5; 95% CI, 1.2 to 5.2; P = 0.02) postoperatively. After adjusting for other covariates, presence of cirrhosis (adjusted odds ratio, 2.2; 95% CI, 1.1 to 4.1) and intraoperative transfusion (adjusted odds ratio, 3.2; 95% CI, 1.6 to 6.3) were independently associated with increased mortality. CONCLUSION: Despite having low median model for end-stage liver disease scores, this small series of cirrhotic patients undergoing cardiac surgery had significantly higher mortality rates and required more organ support postoperatively than propensity score-matched non-cirrhotic patients. Impact de la cirrhose chez les patients subissant une chirurgie cardiaque : une étude de cohorte observationnelle et rétrospective.

Deceased organ donation potential in Canada: a review of consecutive deaths in Alberta.

BACKGROUND: Transplantation is the most effective treatment for many patients with end-stage organ failure. There is a gap between the number of patients who would benefit from transplantation and availability of organs. We assessed maximum potential for deceased donation in Alberta and barriers to increasing the donation rate. METHODS: All deaths that occurred in Alberta in 2015 in areas where mechanical ventilation could be provided were retrospectively identified using administrative data. Medical records were reviewed by donation coordinators and critical care physicians with expertise in donation, using a standardized tool to determine whether deceased patients could potentially have been organ donors. RESULTS: There were 2,706 deaths occurring in either an intensive care unit or emergency department, of which 1,252 were attributable to a non-neurologic cause: 946 involved cardiac arrests with unsuccessful resuscitation, and 57 were not mechanically ventilated. Of the remaining 451 deaths, 117 (28 donors per million population [dpmp]) either were, or could potentially have been, organ donors after neurologic determination of death (NDD). Of these, 19 (4.5 dpmp) were not appropriately identified or referred, and 45 approached families (10.8 dpmp) did not provide consent. Non-identified NDD cases accounted for a larger proportion of deaths due to neurologic causes in emergency departments (18%) than in intensive care units (2%) (P < 0.0001) and in rural (9%) compared with urban centres (3%) (P = 0.05). If routinely available, donation after circulatory death (DCD) could potentially have been possible in as many as 113 (27 dpmp) cases. CONCLUSIONS: Maximum deceased organ donation potential in Alberta is approximately 55 dpmp. The current donation rate has potential to increase with more widespread availability of DCD and a higher consent rate.

Outcomes of elderly critically ill medical and surgical patients: a multicentre cohort study.

PURPOSE: Very elderly (over 80 yr of age) critically ill patients admitted to medical-surgical intensive care units (ICUs) have a high incidence of mortality, prolonged hospital length of stay, and dependent living conditions should they survive. The primary purpose of this study is to describe the outcomes and differences in outcomes between very elderly medical patients and their surgical counterparts admitted to Canadian ICUs, thereby informing decision-making for clinicians and substitute decision-makers. METHODS: This was a prospective multicentre cohort study of very elderly medical and surgical patients admitted to 22 Canadian academic and non-academic ICUs. Outcome measures included ICU length of stay and mortality, hospital length of stay and mortality, and disposition following hospital discharge. RESULTS: There were 1,671 patients evaluated in this study. Patient demographics included a mean age of 84.5 yr, baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score of 22.4, baseline Sequential Organ Failure Assessment (SOFA) score of 5.3, overall ICU mortality of 21.8%, and overall hospital mortality of 35.0%. Medical patient median ICU length of stay was 4.1 days, hospital length of stay was 16.2 days, ICU mortality was 26.5%, and hospital mortality was 41.5%. Surgical patient median ICU length of stay was 3.8 days, hospital length of stay was 20.1 days, ICU mortality was 18.7%, and hospital mortality was 31.6%. Only 45.0% of medical patients and 41.6% of surgical emergency patients were able to return home to live. CONCLUSIONS: In this large sample of critically ill medical and surgical patients, the admission SOFA score and hospital lengths of stay were not different between the two groups, but medical patients had longer ICU lengths of stay and higher ICU and hospital mortality than surgical patients.

Risk of Hyponatremia in Patients with Aneurysmal Subarachnoid Hemorrhage Treated with Exogenous Vasopressin Infusion.

BACKGROUND: Vasopressin is one of the vasopressors used to augment blood pressure in subarachnoid hemorrhage (SAH) patients with clinically significant vasospasm. The purpose of the present study was to determine whether the administration of vasopressin to a population of SAH patients was an independent predictor of developing hyponatremia. METHODS: A retrospective review on the health records of 106 patients admitted to the University of Alberta Hospital Neurosciences ICU, Edmonton AB, Canada, with SAH from June 2013 to December 2015 was conducted. Serum sodium changes in patients receiving vasoactive drugs were compared. In addition, independent predictors for hyponatremia (Na < 135 mmol/L) were determined using a multivariate logistic regression model. RESULTS: Patients treated with vasopressin in addition to other vasoactive drugs had significantly higher sodium changes compared to those treated with other vasoactive drugs (-4.7 ± 6 vs -0.1 ± 2.4 mmol/L, respectively, p value 0.001). Hyponatremia occurred in 14 patients (70 %) treated with vasopressin, 10 patients (44 %) treated with vasoactive drugs other than vasopressin (p value 0.081), and 24 patients (38 %) who did not receive any vasoactive drug (p value 0.013). In multivariate logistic regression analysis, when adjusting for disease severity, age, sex, aneurysm location, and treatment, vasopressin was associated with hyponatremia (OR 3.58, 95 % CI, 1.02-12.5, p value 0.046). CONCLUSIONS: The results of the present study suggest that hyponatremia may be more common in SAH patients treated with exogenous vasopressin compared to those who did not receive it. Serum sodium should be monitored closely when vasopressin is being used in the SAH population. Further studies are needed to confirm the effect of exogenous vasopressin on serum sodium levels in SAH populations.

Prevention of Hypoxemia During Apnea Testing: A Comparison of Oxygen Insufflation And Continuous Positive Airway Pressure.

BACKGROUND: Apnea testing is an essential step in the clinical diagnosis of brain death. Current international guidelines recommend placement of an oxygen (O2) insufflation catheter into the endotracheal tube to prevent hypoxemia, but use of a continuous positive airway pressure (CPAP) valve may be more effective at limiting arterial partial pressure of O2 (PO2) reduction. METHODS: We performed a multicenter study assessing consecutive apnea tests in 14 intensive care units (ICUs) in two cities utilizing differing protocols. In one city, O2 catheters are placed and arterial blood gases (ABGs) performed at intervals determined by the attending physician. In the other city, a resuscitation bag with CPAP valve is attached to the endotracheal tube, and ABGs performed every 3-5 min. We assessed arterial PO2, partial pressure of carbon dioxide (PCO2), pH, and blood pressure at the beginning and termination of each apnea test. RESULTS: Thirty-six apnea tests were performed using an O2 catheter and 50 with a CPAP valve. One test per group was aborted because of physiological instability. There were no significant differences in the degree of PO2 reduction (-59 vs. -32 mmHg, p = 0.72), rate of PCO2 rise (3.2 vs. 3.9 mmHg per min, p = 0.22), or pH decline (-0.02 vs. -0.03 per min, p = 0.06). Performance of ABGs at regular intervals was associated with shorter test duration (10 vs. 7 min, p < 0.0001), smaller PCO2 rise (30 vs. 26 mmHg, p = 0.0007), and less pH reduction (-0.20 vs. -0.17, p = 0.0012). Lower pH at completion of the apnea test was associated with greater blood pressure decline (p = 0.006). CONCLUSION: Both methods of O2 supplementation are associated with similar changes in arterial PO2 and PCO2. Performance of ABGs at regular intervals shortens apnea test duration and may avoid excessive pH reduction and consequent hemodynamic effects.

Admission of the very elderly to the intensive care unit: family members' perspectives on clinical decision-making from a multicenter cohort study.

BACKGROUND: Little is known about the perspectives and experiences of family members of very elderly patients who are admitted to the intensive care unit. AIM: To describe family members' perspectives about care provided to very elderly critically ill patients. DESIGN: Multicenter, prospective, cohort study. PARTICIPANTS AND SETTING: In total, 535 family members of patients aged 80 years or older admitted to 22 intensive care units for more than 24 h. RESULTS: Family members reported that the "patient be comfortable and suffer as little as possible" was their most important value and "the belief that life should be preserved at all costs" was their least important value considered in making treatment decisions. Most family members (57.9%) preferred that life support be used for their family member, whereas 24.1% preferred comfort measures only, and 14.4% were unsure of their treatment preferences. Only 57.3% reported that a doctor had talked to them about treatment options for the patient. Overall, 29.7% of patients received life-sustaining treatments for more than 7 days and 50.3% of these died in hospital. Families were most satisfied with the skill and competency of nurses and least satisfied with being included and supported in the decision-making process and with their sense of control over the patient's care. CONCLUSION: There is incongruity between family values and preferences for end-of-life care and actual care received for very elderly patients who are admitted to the intensive care unit. Deficiencies in communication and decision-making may be associated with prolonged use of life-sustaining treatments in very elderly critically ill patients, many of whom ultimately die.

Vital signs after cardiac arrest following withdrawal of life-sustaining therapy: a multicenter prospective observational study.

OBJECTIVE: Controversies regarding the process and timing of the determination of death for controlled organ donation after circulatory death persist. This study assessed the feasibility of conducting a prospective, observational study of continuous monitoring of vital signs for 30 minutes after the clinical determination of death in five Canadian ICUs. Waveform data were analyzed. DESIGN: Prospective observational cohort study. SETTING: One pediatric and four adult Canadian ICUs. PATIENTS: One month of age or older, admitted to the ICU, and for whom a consensual decision to withdraw life-sustaining therapies had been made, with an anticipation of imminent death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive arterial blood pressure, electrocardiogram, and oxygen saturation plethysmography activity were recorded and reviewed for 30 minutes after declaration of death. Feasibility was assessed (recruitment, consent rate, protocol compliance, and staff satisfaction). Of 188 subjects screened over 16 months, 41 subjects were enrolled (87% consent rate). Data collection was complete for 30 subjects (73% protocol compliance). In four subjects, arterial blood pressure resumed following cessation of activity. The longest period of cessation of arterial blood pressure before resumption was 89 seconds. The duration of resumed activity ranged from 1 to 172 seconds. No cases of sustained resumption of arterial blood pressure activity were recorded, and no instances of clinical autoresuscitation were reported. In nearly all patients (27 of 30), electrocardiogram activity continued after the disappearance of arterial blood pressure. CONCLUSIONS: This is the first observational study to prospectively collect waveform data for 30 minutes after the declaration of death. A future larger study may support initial data suggesting that circulatory function does not resume after more than 89 seconds of absence. Furthermore, persistence of cardiac electrical activity with the documented absence of circulation may not be relevant to declaration of death.

A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in patients with sepsis and suspected disseminated intravascular coagulation.

OBJECTIVES: To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. DESIGN: Phase 2b, international, multicenter, double-blind, randomized, placebo-controlled, parallel group, screening trial. SETTING: Two hundred and thirty-three ICUs in 17 countries. PATIENTS: All adult patients admitted with sepsis and suspected disseminated intravascular coagulation as assessed using a modified International Society on Thrombosis and Hemostasis score. INTERVENTIONS: Patients were randomized to receive IV ART-123 (0.06 mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary endpoint was reduction in mortality. Secondary endpoints included reversal of overt disseminated intravascular coagulation and reduction in disease severity. MEASUREMENTS AND MAIN RESULTS: A total of 750 patients were randomized, nine of whom did not receive the allocated treatment so that 371 patients received ART-123 and 370 received placebo. There were no meaningful differences between the two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8% in the ART-123 group and 21.6% in the placebo group (Cochran-Mantel-Haenszel two-sided p value of 0.273 in favor of ART-123, which met the predefined statistical test for evidence suggestive of efficacy). There were no statistically significant differences in event-free and alive days between the two groups. d-dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART-123 group than in the placebo group. There were no differences between the two groups in organ function, inflammatory markers, bleeding or thrombotic events or in the development of new infections. In post hoc analyses, greatest benefit from ART-123 was seen in patients with at least one organ system dysfunction and an international normalized ratio greater than 1.4 at baseline. CONCLUSIONS: ART-123 is a safe intervention in critically ill patients with sepsis and suspected disseminated intravascular coagulation. The study provided evidence suggestive of efficacy supporting further development of this drug in sepsis-associated coagulopathy including disseminated intravascular coagulation. Future study should focus on using ART-123 in the subgroup of patients most likely to respond to this agent.

A systematic review and meta-analysis to assess patient-reported outcomes after lung cancer surgery.

The main objective of this review was to systematically review, assess, and report on the studies that have assessed health related quality of life (HRQOL) after VATS and thoracotomy for resection of lung cancer. We performed a systematic review of six databases. The Downs and Black tool was used to assess the risk of bias. Five studies were included. In general, patients undergoing VATS have a better HRQOL when compared to thoracotomy; however, there was a high risk of bias in the included studies. The consistent use of a lung cancer specific questionnaire for measuring HRQOL after surgery is encouraged.

The relationship between organizational culture and family satisfaction in critical care.

OBJECTIVES: Family satisfaction with critical care is influenced by a variety of factors. We investigated the relationship between measures of organizational and safety culture, and family satisfaction in critical care. We further explored differences in this relationship depending on intensive care unit survival status and length of intensive care unit stay of the patient. DESIGN: Cross-sectional surveys. SETTING: Twenty-three tertiary and community intensive care units within three provinces in Canada. SUBJECTS: One thousand two-hundred eighty-five respondents from 2374 intensive care unit clinical staff, and 880 respondents from 1381 family members of intensive care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intensive care unit staff completed the Organization and Management of Intensive Care Units survey and the Hospital Survey on Patient Safety Culture. Family members completed the Family Satisfaction in the Intensive Care Unit 24, a validated survey of family satisfaction. A priori, we analyzed adjusted relationships between each domain score from the culture surveys and either satisfaction with care or satisfaction with decision-making for each of four subgroups of family members according to patient descriptors: intensive care unit survivors who had length of intensive care unit stay <14 days or >14 days, and intensive care unit nonsurvivors who had length of stay <14 days or ≥14 days. We found strong positive relationships between most domains of organizational and safety culture, and satisfaction with care or decision-making for family members of intensive care unit nonsurvivors who spent at least 14 days in the intensive care unit. For the other three groups, there were only a few weak relationships between domains of organizational and safety culture and family satisfaction. CONCLUSIONS: Our findings suggest that the effect of organizational culture on care delivery is most easily detectable by family members of the most seriously ill patients who interact frequently with intensive care unit staff, who are intensive care unit nonsurvivors, and who spend a longer time in the intensive care unit. Positive relationships between measures of organizational and safety culture and family satisfaction suggest that by improving organizational culture, we may also improve family satisfaction.

Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19.

Purpose: There may be a difference in respiratory mechanics, inflammatory markers, and pulmonary emboli in COVID-19 associated ARDS vs. ARDS from other etiologies. Our purpose was to determine differences in respiratory mechanics, inflammatory markers, and incidence of pulmonary embolism in patients with and without COVID-19 associated ARDS admitted in the same period and treated with a similar ventilation strategy. Methods: A cohort study of COVID-19 associated ARDS and non COVID-19 patients in a Saudi Arabian center between June 1 and 15, 2020. We measured respiratory mechanics (ventilatory ratio (VR), recruitability index (RI), markers of inflammation, and computed tomography pulmonary angiograms. Results: Forty-two patients with COVID-19 and 43 non-COVID patients with ARDS comprised the cohort. The incidence of "recruitable" patients using the recruitment/inflation ratio was slightly lower in COVID-19 patients (62 vs. 86%; p = 0.01). Fifteen COVID-19 ARDS patients (35.7%) developed a pulmonary embolism as compared to 4 (9.3%) in other ARDS patients (p = 0.003). In COVID-19 patients, a D-Dimer ≥ 5.0 mcg/ml had a 73% (95% CI 45-92%) sensitivity and 89% (95% CI 71-98%) specificity for predicting pulmonary embolism. Crude 60-day mortality was higher in COVID-19 patients (35 vs. 15%; p = 0.039) but three multivariate analysis showed that independent predictors of 60-day mortality included the ventilatory ratio (OR 3.67, 95% CI 1.61-8.35), PaO2/FIO2 ratio (OR 0.93; 95% CI 0.87-0.99), IL-6 (OR 1.02, 95% CI 1.00-1.03), and D-dimer (OR 7.26, 95% CI 1.11-47.30) but not COVID-19 infection. Conclusion: COVID-19 patients were slightly less recruitable and had a higher incidence of pulmonary embolism than those with ARDS from other etiologies. A high D-dimer was predictive of pulmonary embolism in COVID-19 patients. COVID-19 infection was not an independent predictor of 60-day mortality in the presence of ARDS.

Haemoglobin transfusion threshold in traumatic brain injury optimisation (HEMOTION): a multicentre, randomised, clinical trial protocol.

INTRODUCTION: Traumatic brain injury (TBI) is the leading cause of mortality and long-term disability in young adults. Despite the high prevalence of anaemia and red blood cell transfusion in patients with TBI, the optimal haemoglobin (Hb) transfusion threshold is unknown. We undertook a randomised trial to evaluate whether a liberal transfusion strategy improves clinical outcomes compared with a restrictive strategy. METHODS AND ANALYSIS: HEMOglobin Transfusion Threshold in Traumatic Brain Injury OptimizatiON is an international pragmatic randomised open label blinded-endpoint clinical trial. We will include 742 adult patients admitted to an intensive care unit (ICU) with an acute moderate or severe blunt TBI (Glasgow Coma Scale ≤12) and a Hb level ≤100 g/L. Patients are randomly allocated using a 1:1 ratio, stratified by site, to a liberal (triggered by Hb ≤100 g/L) or a restrictive (triggered by Hb ≤70 g/L) transfusion strategy applied from the time of randomisation to the decision to withdraw life-sustaining therapies, ICU discharge or death. Primary and secondary outcomes are assessed centrally by trained research personnel blinded to the intervention. The primary outcome is the Glasgow Outcome Scale extended at 6 months. Secondary outcomes include overall functional independence measure, overall quality of life (EuroQoL 5-Dimension 5-Level; EQ-5D-5L), TBI-specific quality of life (Quality of Life after Brain Injury; QOLIBRI), depression (Patient Health Questionnaire; PHQ-9) and mortality. ETHICS AND DISSEMINATION: This trial is approved by the CHU de Québec-Université Laval research ethics board (MP-20-2018-3706) and ethic boards at all participating sites. Our results will be published and shared with relevant organisations and healthcare professionals. TRIAL REGISTRATION NUMBER: NCT03260478.