Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).

Meningitis in critically ill patients admitted to intensive care unit for severe community-acquired pneumococcal pneumonia.

BACKGROUND: Although it has been reported that patients with pneumococcal pneumonia may develop meningitis, lumbar puncture is not systematically recommended in these patients, even in patients with associated bacteremia or invasive pneumococcal disease. The aim of this study was to determine the characteristics and outcomes of patients admitted to intensive care unit (ICU) for pneumococcal community-acquired pneumonia who developed meningitis. METHODS: We retrospectively included all consecutive patients admitted to our ICU from January 2006 to December 2020 for severe pneumococcal community-acquired pneumonia according to American Thoracic Society criteria. Meningitis was defined as pleocytosis > 5 cells/mm3 or a positive culture of cerebrospinal fluid for Streptococcus pneumoniae in lumbar puncture. The primary endpoint was the proportion of patients with meningitis during their ICU stay. RESULTS: Overall, 262 patients [64(52-75) years old] were included: 154(59%) were male, 80(30%) had chronic respiratory disease, 105(39%) were immunocompromised and 6(2%) were vaccinated against S. pneumoniae. A lumbar puncture was performed in 88(34%) patients with a delay from ICU admission to puncture lumbar of 10.5 (2.8-24.1) h and after the initiation of pneumococcal antibiotherapy in 81(92%) patients. Meningitis was diagnosed in 14 patients: 16% of patients with lumbar puncture and 5% of patients in the whole population. Patients with meningitis had more frequently human immunodeficiency virus positive status (29 vs. 5%, p = 0.02), neurological deficits on ICU admission (43 vs. 16%, p = 0.03) and pneumococcal bacteremia (71 vs. 30%, p < 0.01) than those without. The ICU mortality rate (14 vs. 13%, p = 0.73) and the mortality rate at Day-90 (21 vs. 15%, p = 0.83) did not differ between patients with and without meningitis. The proportion of patients with neurological disorders at ICU discharge was higher in patients with meningitis (64 vs. 23%, p < 0.001) than in those without. The other outcomes did not differ at ICU discharge, Day-30 and Day-90 between the two groups of patients. CONCLUSION: Meningitis was diagnosed in 16% of patients with severe pneumococcal community-acquired pneumonia in whom a lumbar puncture was performed, was more frequent in patients with pneumococcal bacteremia and was associated with more frequent neurological disorders at ICU discharge. Further studies are needed to confirm these results.

Impact of COVID-19 on the association between pulse oximetry and arterial oxygenation in patients with acute respiratory distress syndrome.

Managing patients with acute respiratory distress syndrome (ARDS) requires frequent changes in mechanical ventilator respiratory settings to optimize arterial oxygenation assessed by arterial oxygen partial pressure (PaO2) and saturation (SaO2). Pulse oxymetry (SpO2) has been suggested as a non-invasive surrogate for arterial oxygenation however its accuracy in COVID-19 patients is unknown. In this study, we aimed to investigate the influence of COVID-19 status on the association between SpO2 and arterial oxygenation. We prospectively included patients with ARDS and compared COVID-19 to non-COVID-19 patients, regarding SpO2 and concomitant arterial oxygenation (SaO2 and PaO2) measurements, and their association. Bias was defined as mean difference between SpO2 and SaO2 measurements. Occult hypoxemia was defined as a SpO2 ≥ 92% while concomitant SaO2 < 88%. Multiple linear regression models were built to account for confounders. We also assessed concordance between positive end-expiratory pressure (PEEP) trial-induced changes in SpO2 and in arterial oxygenation. We included 55 patients, among them 26 (47%) with COVID-19. Overall, SpO2 and SaO2 measurements were correlated (r = 0.70; p < 0.0001), however less so in COVID-19 than in non-COVID-19 patients (r = 0.55, p < 0.0001 vs. r = 0.84, p < 0.0001, p = 0.002 for intergroup comparison). Bias was + 1.1%, greater in COVID-19 than in non-COVID-19 patients (2.0 vs. 0.3%; p = 0.02). In multivariate analysis, bias was associated with COVID-19 status (unstandardized ß = 1.77, 95%CI = 0.38-3.15, p = 0.01), ethnic group and ARDS severity. Occult hypoxemia occurred in 5.5% of measurements (7.7% in COVID-19 patients vs. 3.4% in non-COVID-19 patients, p = 0.42). Concordance rate between PEEP trial-induced changes in SpO2 and SaO2 was 84%, however less so in COVID-19 than in non-COVID-19 patients (69% vs. 97%, respectively). Similar results were observed for PaO2 regarding correlations, bias, and concordance with SpO2 changes. In patients with ARDS, SpO2 was associated with arterial oxygenation, but COVID-19 status significantly altered this association.

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study.

PURPOSE: To study prevalence of targeted therapy (TT)-related adverse events requiring ICU admission in solid tumor patients. METHODS: Retrospective multicenter study from the Nine-i research group. Adult patients who received TT for solid tumor within 3 months prior to ICU admission were included. Patients admitted for TT-related adverse event were compared to those admitted for other reasons. RESULTS: In total, 140 patients, median age of 63 (52-69) years were included. Primary cancer site was mostly digestive (n=27, 19%), kidney (n=27, 19%), breast (n=24, 17%), and lung (n=20, 14%). Targeted therapy was anti-VEGF/VEGFR for 27% (n=38) patients, anti-EGFR for 22% (n=31) patients, anti-HER2 for 14% (n=20) patients and anti-BRAF for 9% (n=5) patients. ICU admission was related to TT adverse events for 30 (21%) patients. The most frequent complications were interstitial pneumonia (n=7), cardiac failure (n=5), anaphylaxis (n=4) and bleeding (n=4). At ICU admission, no significant difference was found between patients admitted for a TT-related adverse event and the other patients. One-month survival rate was higher in patients admitted for TT adverse event (OR=5.733 [2.031-16.182] P<0.001). CONCLUSIONS: Adverse events related to targeted therapy accounted for 20% of ICU admission in our population and carried a 16% one-month mortality. Outcome was associated with admission for TT related to adverse event, breast cancer and good performance status.

Accuracy of clinicians' ability to predict the need for renal replacement therapy: a prospective multicenter study.

PURPOSE: Identifying patients who will receive renal replacement therapy (RRT) during intensive care unit (ICU) stay is a major challenge for intensivists. The objective of this study was to evaluate the performance of physicians in predicting the need for RRT at ICU admission and at acute kidney injury (AKI) diagnosis. METHODS: Prospective, multicenter study including all adult patients hospitalized in 16 ICUs in October 2020. Physician prediction was estimated at ICU admission and at AKI diagnosis, according to a visual Likert scale. Discrimination, risk stratification and benefit of physician estimation were assessed. Mixed logistic regression models of variables associated with risk of receiving RRT, with and without physician estimation, were compared. RESULTS: Six hundred and forty-nine patients were included, 270 (41.6%) developed AKI and 77 (11.8%) received RRT. At ICU admission and at AKI diagnosis, a model including physician prediction, the experience of the physician, SOFA score, serum creatinine and diuresis to determine need for RRT performed better than a model without physician estimation with an area under the ROC curve of 0.90 [95% CI 0.86-0.94, p < 0.008 (at ICU admission)] and 0.89 [95% CI 0.83-0.93, p = 0.0014 (at AKI diagnosis)]. In multivariate analysis, physician prediction was strongly associated with the need for RRT, independently of creatinine levels, diuresis, SOFA score and the experience of the doctor who made the prediction. CONCLUSION: As physicians are able to stratify patients at high risk of RRT, physician judgement should be taken into account when designing new randomized studies focusing on RRT initiation during AKI.

Computed tomography after severe COVID-19 pneumonia: findings at 6†months and beyond.

Parenchymal bands and ground-glass opacities consistent with a pattern of late organising pneumonia are frequently observed 6 months after ICU admission for #COVID19, whereas fibrotic changes of limited extent are only observed in about 1/3 of patients https://bit.ly/2UGOsbr.

Association between previous health condition and outcome after cardiac arrest.

INTRODUCTION: Overall survival of patients with out-of-hospital cardiac arrest (OHCA) remains low, even in those with return of spontaneous circulation (ROSC). In addition to usual prognostic characteristics, patients' medical history may also influence their outcome. This study aimed to investigate the role of pre-arrest comorbidities on hospital survival, neurological outcome and mode of death in OHCA patients with successful ROSC. METHODS: From Jan 2012 to Sep 2017, all consecutive non-traumatic OHCA adults, admitted with a stable ROSC were included. Utstein characteristics, circumstances of arrest and interventions were prospectively recorded. Prior comorbidities were measured using the Charlson Comorbidity Index (CCI), and the population was divided into 3 groups (CCI 0, CCI 1-3 and CCI ≥ 4). The association of CCI with early and long-term mortality was assessed using logistic regression and association with withdrawal-of-life sustaining treatments (WLST) or another cause of death using multinomial regression. RESULTS: During the study period, 777 patients were analyzed and 483 (62%) died before hospital discharge, with death rate of 49%, 60% and 70% in CCI 0, CCI 1-3 and CCI ≥ 4 respectively. After adjustment, an increase CCI was significantly associated with in-hospital mortality (OR = 2.47 [1.35-4.52], p = 0.001 for CCI 1-3; OR = 2.82 [1.49-5.33], p = 0.003 for CCI ≥ 4; ref = CCI 0). Other independent predictors were non-shockable rhythm (OR = 3.23 [2.08-5]), lack of bystander CPR (OR = 1.96 [1.22-3.13]), epinephrine dose ≥ 2 mg (OR = 5.56 [3.70-8.33]), CA to CPR ≥ 5 min (OR = 1.96 [1.28-3.03]) and CPR to ROSC ≥ 20 min (OR = 2.13 [1.39-3.23]). Using multinomial regression, an increase in CCI was associated with all modes of in-hospital death, particularly with WLST-related death (RRadj = 2.48 [1.26-4.90], p = 0.01 for CCI = 1-3 and 3.75 [1.85-8.7.58], p < 0.001 for CCI ≥ 4, reference CCI = 0). CONCLUSION: Alteration of chronic health status, as assessed by an elevated CCI, was associated with a higher mortality and a worse neurological outcome in OHCA patients. Presence and burden of comorbidities should be considered in the evaluation of the prognosis in patients admitted in hospital after cardiac arrest.

Frequency, risk factors, and outcomes of non-occlusive mesenteric ischaemia after cardiac arrest.

PURPOSE: Mesenteric ischaemia after successfully resuscitated cardiac arrest (CA) has been insufficiently studied. We aimed to assess the frequency, risk factors, and outcomes of non-occlusive mesenteric ischaemia (NOMI) after CA. METHODS: We retrospectively included patients admitted to a CA centre with sustained return of spontaneous circulation between 2007 and 2017. NOMI was suspected based on clinical symptoms and classified as possible if no tests were feasible or the only test was a negative abdominal computed tomography (CT) scan and as confirmed if diagnosed by endoscopy, CT, or surgery. RESULTS: Of 1343 patients, 82 (6%) had suspected NOMI, including 33 (2.5%) with confirmed NOMI. Investigations for suspected NOMI were done in 47/82 (57%) patients (CT, n = 30; lower digestive endoscopy, n = 14; and upper digestive endoscopy, n = 12); 11 patients underwent surgery. By multivariate analysis, factors associated with suspected NOMI were female sex (OR, 1.8; 95%CI, 1.1-2.9, p = 0.02), cardiovascular comorbidities (OR, 1.6; 95%CI, 1.0-2.7; p = 0.047), admission lactate >5 mmol/L (OR, 2.0; 95%CI, 1.2-3.4; p = 0.01), low flow >17 min (OR, 2.2; 95%CI, 1.3-3.8; p = 0.003), and inotropic score >7 µg/kg/min (OR, 1.8; 95%CI, 1.1-3.2; p = 0.03). ICU mortality was 96% (79/82), with 61% of patients dying from multi-organ failure (MOF) and 35% from post-anoxic brain injury. Of the eight patients who regained consciousness, 5 finally died from MOF, leaving 3 patients discharged alive from the ICU with a good neurologic outcome. CONCLUSIONS: NOMI may affect 2.5-6% of patients after CA. Mortality was extremely high in patients, and very few survived with a good neurological outcome.

Use of Venovenous Extracorporeal Membrane Oxygenation in Critically-Ill Patients With COVID-19.

Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3-11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3-5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0-6.3] to 3.4 [2.5-3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO2/FiO2 ratio significantly increased from 68 [58-89] to 168 [137-218] and the oxygenation index significantly decreased from 28 [26-35] to 13 [10-15]. The duration of ECMO was 12 [8-25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.