Electrocardiographic Changes at the Early Stage of Status Epilepticus: First Insights From the ICTAL Registry.

OBJECTIVES: To describe early electrocardiogram (ECG) abnormalities after status epilepticus (SE) and evaluate their association with 90-day neurological outcomes. DESIGN: Retrospective analysis of a multicenter, national prospective registry between February 2018 and June 2020. SETTING: Sixteen ICUs in France, IctalGroup Research Network. PATIENTS: Adults with available ECG performed less than or equal to 24 hours after the onset of SE and less than or equal to 12 hours after its resolution. INTERVENTION: Double-blinded review of all ECGs was performed by two independent cardiologists. ECGs were categorized as normal/abnormal and then with minor/major early ECG abnormalities according to the Novacode ECG Classification system. MEASUREMENTS AND MAIN RESULTS: Among 155 critically ill patients with SE, early ECG abnormalities were encountered in 145 (93.5%), categorized as major in 91 of 145 (62.8%). In addition to sinus tachycardia, the main abnormalities were in the ST segment (elevation [16.6%] or depression [17.9%]) or negative T waves (42.1%). Major early ECG abnormalities were significantly associated with respiratory distress and sinus tachycardia at the scene and hyperlactatemia at ICU admission. By multivariable analysis, three variables were significantly associated with 90-day poor outcome: age, preexisting ultimately fatal comorbidity, and cerebral insult as the cause of SE. Early major ECG abnormalities were not independently associated with 90-day functional outcome. CONCLUSIONS: In our study, early ECG abnormalities in the acute phase of SE were frequent, often unrecognized and were associated with clinical and biological stigma of hypoxemia. Although they were not independently associated with 90-day functional outcome, ECG changes at the early stage of SE should be systematically evaluated. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03457831 .

Barotrauma in COVID-19 acute respiratory distress syndrome: retrospective analysis of the COVADIS prospective multicenter observational database.

BACKGROUND: Despite evidence suggesting a higher risk of barotrauma during COVID-19-related acute respiratory distress syndrome (ARDS) compared to ARDS due to other causes, data are limited about possible associations with patient characteristics, ventilation strategy, and survival. METHODS: This prospective observational multicenter study included consecutive patients with moderate-to-severe COVID-19 ARDS requiring invasive mechanical ventilation and managed at any of 12 centers in France and Belgium between March and December 2020. The primary objective was to determine whether barotrauma was associated with ICU mortality (censored on day 90), and the secondary objective was to identify factors associated with barotrauma. RESULTS: Of 586 patients, 48 (8.2%) experienced barotrauma, including 35 with pneumothorax, 23 with pneumomediastinum, 1 with pneumoperitoneum, and 6 with subcutaneous emphysema. Median time from mechanical ventilation initiation to barotrauma detection was 3 [0-17] days. All patients received protective ventilation and nearly half (23/48) were in volume-controlled mode. Barotrauma was associated with higher hospital mortality (P < 0.001) even after adjustment on age, sex, comorbidities, PaO2/FiO2 at intubation, plateau pressure at intubation, and center (P < 0.05). The group with barotrauma had a lower mean body mass index (28.6 ± 5.8 vs. 30.3 ± 5.9, P = 0.03) and a higher proportion of patients given corticosteroids (87.5% vs. 63.4%, P = 0.001). CONCLUSION: Barotrauma during mechanical ventilation for COVID-19 ARDS was associated with higher hospital mortality.

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study.

BACKGROUND: Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. METHODS: In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. RESULTS: The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98-1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13-3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88-0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. CONCLUSION: In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.

Intravascular Complications of Central Venous Catheterization by Insertion Site.

BACKGROUND: Three anatomical sites are commonly used to insert central venous catheters, but insertion at each site has the potential for major complications. METHODS: In this multicenter trial, we randomly assigned nontunneled central venous catheterization in patients in the adult intensive care unit (ICU) to the subclavian, jugular, or femoral vein (in a 1:1:1 ratio if all three insertion sites were suitable [three-choice scheme] and in a 1:1 ratio if two sites were suitable [two-choice scheme]). The primary outcome measure was a composite of catheter-related bloodstream infection and symptomatic deep-vein thrombosis. RESULTS: A total of 3471 catheters were inserted in 3027 patients. In the three-choice comparison, there were 8, 20, and 22 primary outcome events in the subclavian, jugular, and femoral groups, respectively (1.5, 3.6, and 4.6 per 1000 catheter-days; P=0.02). In pairwise comparisons, the risk of the primary outcome was significantly higher in the femoral group than in the subclavian group (hazard ratio, 3.5; 95% confidence interval [CI], 1.5 to 7.8; P=0.003) and in the jugular group than in the subclavian group (hazard ratio, 2.1; 95% CI, 1.0 to 4.3; P=0.04), whereas the risk in the femoral group was similar to that in the jugular group (hazard ratio, 1.3; 95% CI, 0.8 to 2.1; P=0.30). In the three-choice comparison, pneumothorax requiring chest-tube insertion occurred in association with 13 (1.5%) of the subclavian-vein insertions and 4 (0.5%) of the jugular-vein insertions. CONCLUSIONS: In this trial, subclavian-vein catheterization was associated with a lower risk of bloodstream infection and symptomatic thrombosis and a higher risk of pneumothorax than jugular-vein or femoral-vein catheterization. (Funded by the Hospital Program for Clinical Research, French Ministry of Health; ClinicalTrials.gov number, NCT01479153.).

Cardiac Arrest in Patients Managed for Convulsive Status Epilepticus: Characteristics, Predictors, and Outcome.

OBJECTIVES: Cardiac arrest is a catastrophic event that may arise during the management of convulsive status epilepticus. We aimed to report the clinical characteristics, outcomes, and early predictors of convulsive status epilepticus-related cardiac arrest. DESIGN: Retrospective multicenter study. SETTING: Seventeen university or university affiliated participating ICUs in France and Belgium. PATIENTS: Consecutive patients admitted to the participating ICUs for management of successfully resuscitated out-of-hospital cardiac arrest complicating the initial management of convulsive status epilepticus between 2000 and 2015. Patients were compared with controls without cardiac arrest identified in a single-center registry of convulsive status epilepticus patients, regarding characteristics, management, and outcome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 49 cases with convulsive status epilepticus-cardiac arrest and 235 controls. In the cases, median time from medical team arrival to cardiac arrest was 25 minutes (interquartile range, 5-85 min). First recorded rhythm was asystole in 25 patients (51%) and pulseless electrical activity in 13 patients (27%). A significantly larger proportion of patients had a favorable 1-year outcome (Glasgow Outcome Scale score of 5) among controls (90/235; 38%) than among cases (10/49; 21%; p = 0.02). By multivariate analysis, independent predictors of cardiac arrest were pulse oximetry less than 97% on scene (odds ratio, 2.66; 95% CI, 1.03-7.26; p = 0.04), drug poisoning as the cause of convulsive status epilepticus (odds ratio, 4.13; 95% CI, 1.27-13.53; p = 0.02), and complications during early management (odds ratio, 11.98; 95% CI, 4.67-34.69; p < 0.0001). Having at least one comorbidity among cardiac, respiratory, and neurologic (other than epilepsy) conditions predicted absence of cardiac arrest (odds ratio, 0.28; 95% CI, 0.10-0.80; p = 0.02). CONCLUSIONS: In patients managed for convulsive status epilepticus, relative hypoxemia, on-scene management complications, and drug poisoning as the cause of convulsive status epilepticus were strong early predictors of cardiac arrest, suggesting areas for improvement.

Sodium Bicarbonate Versus Sodium Chloride for Preventing Contrast-Associated Acute Kidney Injury in Critically Ill Patients: A Randomized Controlled Trial.

OBJECTIVES: To test whether hydration with bicarbonate rather than isotonic sodium chloride reduces the risk of contrast-associated acute kidney injury in critically ill patients. DESIGN: Prospective, double-blind, multicenter, randomized controlled study. SETTING: Three French ICUs. PATIENTS: Critically ill patients with stable renal function (n = 307) who received intravascular contrast media. INTERVENTIONS: Hydration with 0.9% sodium chloride or 1.4% sodium bicarbonate administered with the same infusion protocol: 3 mL/kg during 1 hour before and 1 mL/kg/hr during 6 hours after contrast medium exposure. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the development of contrast-associated acute kidney injury, as defined by the Acute Kidney Injury Network criteria, 72 hours after contrast exposure. Patients randomized to the bicarbonate group (n = 151) showed a higher urinary pH at the end of the infusion than patients randomized to the saline group (n = 156) (6.7 ± 2.1 vs 6.2 ± 1.8, respectively; p < 0.0001). The frequency of contrast-associated acute kidney injury was similar in both groups: 52 patients (33.3%) in the saline group and 53 patients (35.1%) in the bicarbonate group (absolute risk difference, -1.8%; 95% CI [-12.3% to 8.9%]; p = 0.81). The need for renal replacement therapy (five [3.2%] and six [3.9%] patients; p = 0.77), ICU length of stay (24.7 ± 22.9 and 23 ± 23.8 d; p = 0.52), and mortality (25 [16.0%] and 24 [15.9%] patients; p > 0.99) were also similar between the saline and bicarbonate groups, respectively. CONCLUSIONS: Except for urinary pH, none of the outcomes differed between the two groups. Among ICU patients with stable renal function, the benefit of using sodium bicarbonate rather than isotonic sodium chloride for preventing contrast-associated acute kidney injury is marginal, if any.

Pheochromocytoma Crisis in the ICU: A French Multicenter Cohort Study With Emphasis on Rescue Extracorporeal Membrane Oxygenation.

OBJECTIVES: To describe the characteristics, management, and outcome of patients admitted to ICUs for pheochromocytoma crisis. DESIGN: A 16-year multicenter retrospective study. SETTING: Fifteen university and nonuniversity ICUs in France. PATIENTS: Patients admitted in ICU for pheochromocytoma crisis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We included 34 patients with a median age of 46 years (40-54 yr); 65% were males. At admission, the median Sequential Organ Failure Assessment score was 8 (4-12) and median Simplified Acute Physiology Score II 49.5 (27-70). The left ventricular ejection fraction was consistently decreased with a median value of 30% (15-40%). Mechanical ventilation was required in 23 patients, mainly because of congestive heart failure. Vasoactive drugs were used in 23 patients (68%) and renal replacement therapy in eight patients (24%). Extracorporeal membrane oxygenation was used as a rescue therapy in 14 patients (41%). Pheochromocytoma was diagnosed by CT in 33 of 34 patients. When assayed, urinary metanephrine and catecholamine levels were consistently elevated. Five patients underwent urgent surgery, including two during extracorporeal membrane oxygenation. Overall ICU mortality was 24% (8/34), and overall 90-day mortality was 27% (9/34). Crude 90-day mortality was not significantly different between patients managed with versus without extracorporeal membrane oxygenation (22% vs 30%) (p = 0.7) despite higher severity scores at admission in the extracorporeal membrane oxygenation group. CONCLUSIONS: Mortality is high in pheochromocytoma crisis. Routinely considering this diagnosis and performing abdominal CT in patients with unexplained cardiogenic shock may allow an earlier diagnosis. Extracorporeal membrane oxygenation and adrenalectomy should be considered as a therapeutic in most severe cases.

High Level of Endotoxemia Following Out-of-Hospital Cardiac Arrest Is Associated With Severity and Duration of Postcardiac Arrest Shock.

OBJECTIVE: To investigate the contribution of endotoxemia to the severity of postcardiac arrest shock. DESIGN: A prospective monocentric study. SETTING: A tertiary hospital in Paris, France. PATIENTS: Patients admitted in our ICU after a successfully resuscitated out-of-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endotoxin measurement was performed in the 12 hours following return of spontaneous circulation using the endotoxin activity assay. Endotoxin level was classified as low (< 0.4 endotoxin activity), intermediate (0.4 to < 0.6 endotoxin activity), or high (≥ 0.6 endotoxin activity) according to manufacture guidelines. Severity of shock was assessed by the vasopressor-free days and by the mean daily dose of vasopressor to insure a mean arterial pressure of 65-75 mm Hg. Among 92 patients included in the study, 60 presented a postcardiac arrest shock. Endotoxemia level was higher in patients with postcardiac arrest shock. Among these patients, by multivariate linear regression, high endotoxin class (adjusted estimate -2.0; 95% CI, -3.90 to -0.11), public place of cardiac arrest (adjusted estimate, 1.47; 95% CI, 0.007 to 2.93), and time to return of spontaneous circulation (adjusted estimate -0.08; 95% CI, -0.13 to -0.03) were independently associated with the number of vasopressor-free days. Furthermore, high endotoxin class (adjusted estimate, 97.95; 95% CI, 20.5 to 175.4) and a nonshockable rhythm (adjusted estimate, 59.9; 95% CI, 6.2 to 113.7) were the sole factors independently associated with the mean daily dose of vasopressors. CONCLUSIONS: In patients successfully resuscitated from cardiac arrest with a postcardiac arrest shock, high level of endotoxemia is independently associated with duration of postcardiac arrest shock and the amount of vasopressive drugs. Whether treatment targeting endotoxemia could be beneficial in the management of postcardiac arrest shock needs to be studied in further randomized controlled studies.

Out-of-hospital cardiac arrest from brain cause: epidemiology, clinical features, and outcome in a multicenter cohort*.

OBJECTIVES: Although sudden cardiac death has been broadly studied, little is known on cerebrovascular events revealed by out-of-hospital cardiac arrest. We aimed to describe clinical features and prognosis of these patients and identify characteristics that could suggest a cerebrovascular etiology of the out-of-hospital cardiac arrest. DESIGN: Retrospective review (1999-2012) of databases of three regional referral ICU centers for out-of-hospital cardiac arrest. SETTING: Patients admitted to ICU for management of successfully resuscitated out-of-hospital cardiac arrest. PATIENTS: Patients were included when subarachnoid hemorrhage, intracranial hemorrhage, ischemic stroke, sub/epidural hematoma, or cerebral thrombophlebitis was identified as the primary cause of out-of-hospital cardiac arrest. Traumatic or infectious causes were excluded. Patients were compared with a group of out-of-hospital cardiac arrest of nonneurological origin. INTERVENTIONS: All medical records of the three prospective ICU databases, registered according to the Utstein style, were reviewed. MEASUREMENTS AND MAIN RESULTS: Among 3,710 patients admitted for out-of-hospital cardiac arrest, 86 were included (mainly subarachnoid hemorrhage, n = 73). Prodromes were mostly neurological but falsely evoked a cardiac origin in six patients. Electrocardiogram displayed abnormalities in 64% of patients, with 23% of pseudoischemic pattern (ST-segment elevation or left bundle branch block). Mortality rate was 100%, with brain death as the leading cause. In comparison with the nonneurological out-of-hospital cardiac arrest group, female gender, onset of neurological prodromes, lack of other prodromes, initial nonshockable rhythm, and unspecific electrocardiogram repolarization abnormalities were independent predictive factors of a primary cerebrovascular etiology. When present, the combination of these elements displayed an area under the receiver operating characteristic curve of 0.86 (95% CI, 0.81-0.91). CONCLUSIONS: Presentation of cerebrovascular event complicated with out-of-hospital cardiac arrest may mimic coronary etiology, but several clinical elements may help to identify brain causes. Even if survival is null, the high proportion of brain deaths provides opportunity for organ donation.

Quasi-experimental study of sodium citrate locks and the risk of acute hemodialysis catheter infection among critically ill patients.

Critically ill patients who require renal replacement therapy (RRT) are vulnerable to catheter-related bloodstream infections (CRBSI). This study compared the risks of dialysis catheter infection according to the choice of locking solution in the intensive care unit (ICU). A prospective quasi-experimental study with marginal structural models (MSM) and 2:1 greedy propensity-score matching (PSM) was conducted at nine university-affiliated hospitals and three general hospitals. A total of 596 critically ill patients received either saline solution or heparin lock solution (the standard of care [SOC]) from 2004 to 2007 in the Cathedia cohort (n = 464 for MSM; n = 124 for PSM) or 46.7% citrate lock from 2011 to 2012 in the citrate (CLock) cohort (n = 132 for MSM; n = 62 for PSM) to perform RRT using intermittent hemodialysis. Catheter-tip colonization and CRBSI were analyzed. The mean duration (standard deviation [SD]) of catheterization was 7.1 days (6.1) in the SOC group and 7.0 days (5.9) in the CLock group (P = 0.84). The risk of dialysis catheter-tip colonization was lower in the CLock group (20.5 versus 38.7 per 1,000 catheter-days in the SOC group; hazard ratio [HR] from MSM, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P < 0.02). Consistent findings were found from PSM (HR, 0.46; 95% CI, 0.22 to 0.95; P < 0.04). The risk of CRBSI was nonsignificantly different in the CLock group (1.1 versus 1.8 per 1,000 catheter-days in the SOC group; HR from MSM, 0.48; 95% CI, 0.12 to 1.87; P = 0.29). By reducing the risk of catheter-tip colonization, citrate lock has the potential to improve hemodialysis safety in the ICU. Additional studies are warranted before the routine use of citrate locks can be recommended in the ICU.

Noninvasive ventilation and breathing-swallowing interplay in chronic obstructive pulmonary disease*.

OBJECTIVES: To investigate breathing-swallowing interactions in patients with chronic obstructive pulmonary disease requiring noninvasive mechanical ventilation and, if needed, to develop a technical modification of the ventilator designed to eliminate ventilator insufflations during swallowing. DESIGN: We conducted a prospective, open-label, interventional study. PATIENTS: Fifteen consecutive chronic obstructive pulmonary disease patients with exacerbations requiring ICU admission and NIV. INTERVENTIONS: Swallowing performance and breathing-swallowing interactions were investigated noninvasively by chin electromyography, cervical piezoelectric sensor, and inductive respiratory plethysmography. Two water-bolus sizes (5 and 10 mL) were tested in random order. Swallowing was tested with and without noninvasive mechanical ventilation, in random order. First, a standard mechanical ventilator capable of delivering noninvasive mechanical ventilation was used. Second, a marketed device was equipped with an off-switch for use during swallowing. MEASUREMENTS AND MAIN RESULTS: Swallowing performance and breathing-swallowing interactions were investigated noninvasively by chin electromyography, cervical piezoelectric sensor, and inductive respiratory plethysmography. Two water bolus sizes (5 and 10 mL) were tested in random order. Swallowing was tested with and without noninvasive mechanical ventilation in random order. First, a standard mechanical ventilator capable of delivering noninvasive mechanical ventilation was used. Swallowing efficiency, breathing-swallowing synchronization, and Borg Scale dyspnea scores improved significantly with noninvasive mechanical ventilation. However, swallowing induced ventilator triggering followed by autotriggering. To improve patient-ventilator synchrony, a marketed device was equipped with an off-switch for use during swallowing. This device completely eliminated swallowing-induced ventilator triggering and postswallow autotriggering. CONCLUSION: Patients with chronic obstructive pulmonary disease admitted to the ICU for acute exacerbations had abnormal breathing-swallowing interactions and dyspnea, which improved with noninvasive mechanical ventilation. Furthermore, a ventilator device with a simple switch-off pushbutton to eliminate insufflations during swallows prevented swallowing-induced ventilator triggering and postswallow autotriggering.

Predictors of functional outcome after intraoperative cardiac arrest.

BACKGROUND: Few outcome data are available about intraoperative cardiac arrest (IOCA). The authors studied 90-day functional outcomes and their determinants in patients admitted to the intensive care unit after IOCA. METHODS: Patients admitted to 11 intensive care units in a period of 2000-2013 were studied retrospectively. The main outcome measure was a day-90 Cerebral Performance Category score of 1 or 2. RESULTS: Of the 140 patients (61 women and 79 men; median age, 60 yr [interquartile range, 46 to 70]), 131 patients (93.6%) had general anesthesia, 80 patients (57.1%) had emergent surgery, and 73 patients (52.1%) had IOCA during surgery. First recorded rhythms were asystole in 73 patients (52.1%), pulseless electrical activity in 44 patients (31.4%), and ventricular fibrillation/ventricular tachycardia in 23 patients (16.4%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation were 0 min (0 to 0) and 10 min (5 to 20), respectively. Postcardiac arrest shock was identified in 114 patients (81.4%). Main causes of IOCA were preoperative complications (n = 46, 32.9%), complications of anesthesia (n = 39, 27.9%), and complications of surgical procedures (n = 36, 25.7%). On day 90, 63 patients (45.3%) were alive with Cerebral Performance Category score 1/2. Independent predictors of day-90 Cerebral Performance Category score 1/2 were day-1 Logistic Organ Dysfunction score (odds ratio, 0.78 per point; 95% CI, 0.71 to 0.87; P = 0.0001), ventricular fibrillation/tachycardia as first recorded rhythm (odds ratio, 4.78; 95% CI, 1.38 to 16.53; P = 0.013), and no epinephrine therapy during postcardiac arrest syndrome (odds ratio, 3.14; 95% CI, 1.29 to 7.65; P = 0.012). CONCLUSIONS: By day 90, 45% of IOCA survivors had good functional outcomes. The main outcome predictors were directly related to IOCA occurrence and postcardiac arrest syndrome; they suggest that the intensive care unit management of postcardiac arrest syndrome may be amenable to improvement.

Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study.

BACKGROUND: Due to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019. RESULTS: One-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001). CONCLUSION: Overall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.

Performance of the ERC/ESICM-recommendations for neuroprognostication after cardiac arrest: Insights from a prospective multicenter cohort.

AIM: To investigate the performance of the 2021 ERC/ESICM-recommended algorithm for predicting poor outcome after cardiac arrest (CA) and potential tools for predicting neurological recovery in patients with indeterminate outcome. METHODS: Prospective, multicenter study on out-of-hospital CA survivors from 28 ICUs of the AfterROSC network. In patients comatose with a Glasgow Coma Scale motor score ≤3 at ≥72 h after resuscitation, we measured: (1) the accuracy of neurological examination, biomarkers (neuron-specific enolase, NSE), electrophysiology (EEG and SSEP) and neuroimaging (brain CT and MRI) for predicting poor outcome (modified Rankin scale score ≥4 at 90 days), and (2) the ability of low or decreasing NSE levels and benign EEG to predict good outcome in patients whose prognosis remained indeterminate. RESULTS: Among 337 included patients, the ERC-ESICM algorithm predicted poor neurological outcome in 175 patients, and the positive predictive value for an unfavourable outcome was 100% [98-100]%. The specificity of individual predictors ranged from 90% for EEG to 100% for clinical examination and SSEP. Among the remaining 162 patients with indeterminate outcome, a combination of 2 favourable signs predicted good outcome with 99[96-100]% specificity and 23[11-38]% sensitivity. CONCLUSION: All comatose resuscitated patients who fulfilled the ERC-ESICM criteria for poor outcome after CA had poor outcome at three months, even if a self-fulfilling prophecy cannot be completely excluded. In patients with indeterminate outcome (half of the population), favourable signs predicted neurological recovery, reducing prognostic uncertainty.

Increased survival of cirrhotic patients with septic shock.

INTRODUCTION: The overall outcome of septic shock has been recently improved. We sought to determine whether this survival gain extends to the high-risk subgroup of patients with cirrhosis. METHODS: Cirrhotic patients with septic shock admitted to a medical intensive care unit (ICU) during two consecutive periods (1997-2004 and 2005-2010) were retrospectively studied. RESULTS: Forty-seven and 42 cirrhotic patients presented with septic shock in 1997-2004 and 2005-2010, respectively. The recent period differed from the previous one by implementation of adjuvant treatments of septic shock including albumin infusion as fluid volume therapy, low-dose glucocorticoids, and intensive insulin therapy. ICU and hospital survival markedly improved over time (40% in 2005-2010 vs. 17% in 1997-2004, P = 0.02 and 29% in 2005-2010 vs. 6% in 1997-2004, P = 0.009, respectively). Furthermore, this survival gain in the latter period was sustained for 6 months (survival rate 24% in 2005-2010 vs. 6% in 1997-2004, P = 0.06). After adjustment with age, the liver disease stage (Child-Pugh score), and the critical illness severity score (SOFA score), ICU admission between 2005 and 2010 remained an independent favorable prognostic factor (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02-0.4, P = 0.004). The stage of the underlying liver disease was also independently associated with hospital mortality (Child-Pugh score: OR 1.42 per point, 95% CI 1.06-1.9, P = 0.018). CONCLUSIONS: In the light of advances in management of both cirrhosis and septic shock, survival of such patients substantially increased over recent years. The stage of the underlying liver disease and the related therapeutic options should be included in the decision-making process for ICU admission.

Toll-like receptor 2 deficiency increases resistance to Pseudomonas aeruginosa pneumonia in the setting of sepsis-induced immune dysfunction.

BACKGROUND: Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host's response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. METHODS: We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild-type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2 4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. RESULTS: Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2 4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor α and decreased release of interleukin 10. CONCLUSIONS: In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung.

Insulin therapy and blood glucose management in critically ill patients: a 1-day cross-sectional observational study in 69 French intensive care units.

BACKGROUND: Hyperglycaemia is common in critically ill patients, but blood glucose and insulin management may differ widely among intensive care units (ICUs). We aimed to describe insulin use practices and the resulting glycaemic control in French ICUs. We conducted a multicentre 1-day observational study on November 23, 2021, in 69 French ICUs. Adult patients hospitalized for an acute organ failure, severe infection or post-operative care were included. Data were recorded from midnight to 11:59 p.m. the day of the study by 4-h periods. RESULTS: Two ICUs declared to have no insulin protocol. There was a wide disparity in blood glucose targets between ICUs with 35 different target ranges recorded. In 893 included patients we collected 4823 blood glucose values whose distribution varied significantly across ICUs (P < 0.0001). We observed 1135 hyperglycaemias (> 1.8 g/L) in 402 (45.0%) patients, 35 hypoglycaemias (≤ 0.7 g/L) in 26 (2.9%) patients, and one instance of severe hypoglycaemia (≤ 0.4 g/L). Four hundred eight (45.7%) patients received either IV insulin (255 [62.5%]), subcutaneous (SC) insulin (126 [30.9%]), or both (27 [6.6%]). Among patients under protocolized intravenous (IV) insulin, 767/1681 (45.6%) of glycaemias were above the target range. Among patients receiving insulin, short- and long-acting SC insulin use were associated with higher counts of hyperglycaemias as assessed by multivariable negative binomial regression adjusted for the propensity to receive SC insulin: incidence rate ratio of 3.45 (95% confidence interval [CI] 2.97-4.00) (P < 0.0001) and 3.58 (95% CI 2.84-4.52) (P < 0.0001), respectively. CONCLUSIONS: Practices regarding blood glucose management varied widely among French ICUs. Administration of short or long-acting SC insulin was not unusual and associated with more frequent hyperglycaemia. The protocolized insulin algorithms used failed to prevent hyperglycaemic events.

Prospective comparison of prognostic scores for prediction of outcome after out-of-hospital cardiac arrest: results of the AfterROSC1 multicentric study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. METHODS: We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. RESULTS: During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76-0.83], whereas AUROCs from other scores varied from 0.79 [0.75-0.83] to 0.88 [0.86-0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. CONCLUSIONS: In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891.