Association of Standard Electroencephalography Findings With Mortality and Command Following in Mechanically Ventilated Patients Remaining Unresponsive After Sedation Interruption.

CONTEXT: Delayed awakening after sedation interruption is frequent in critically ill patients receiving mechanical ventilation. OBJECTIVES: We aimed to investigate the association of standard electroencephalography with mortality and command following in this setting. DESIGN, SETTING, AND PATIENTS: In a single-center study, we retrospectively analyzed standard electroencephalography performed in consecutive mechanically ventilated patients remaining unresponsive (comatose/stuporous or unable to follow commands) after sedation interruption. Standard electroencephalography parameters (background activity, continuity, and reactivity) were reassessed by neurophysiologists, blinded to patients' outcome. Patients were categorized during follow-up into three groups based on their best examination as: 1) command following, 2) unresponsive, or 3) deceased. Cause-specific models were used to identify independent standard electroencephalography parameters associated with main outcomes, that is, mortality and command following. Follow-up was right-censored 30 days after standard electroencephalography. MEASUREMENTS AND MAIN RESULTS: Main standard electroencephalography parameters recorded in 121 unresponsive patients (median time between sedation interruption and standard electroencephalography: 2 d [interquartile range, 1-4 d]) consisted of a background frequency greater than 4 Hz in 71 (59%), a discontinuous background in 19 (16%), and a preserved reactivity in 98/120 (82%) patients. At 30 days, 66 patients (55%) were command following, nine (7%) were unresponsive, and 46 (38%) had died. In a multivariate analysis adjusted for nonneurologic organ failure, a reactive standard electroencephalography with a background frequency greater than 4 Hz was independently associated with a reduced risk of death (cause-specific hazard ratio, 0.38; CI 95%, 0.16-0.9). By contrast, none of the standard electroencephalography parameters were independently associated with command following. Sensitivity analyses conducted after exclusion of 29 patients with hypoxic brain injury revealed similar findings. CONCLUSIONS: In patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with decreased odds of death. None of the standard electroencephalography parameters were independently associated with command following.

Influence of dyskalemia at admission and early dyskalemia correction on survival and cardiac events of critically ill patients.

OBJECTIVES: Our objectives were (1) to characterize the distribution of serum potassium levels at ICU admission, (2) to examine the relationship between dyskalemia at ICU admission and occurrence of cardiac events, and (3) to study both the association between dyskalemia at ICU admission and dyskalemia correction by day 2 on 28-day mortality. DESIGN: Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1999-2014) SETTING: 22 French OUTCOMEREA network ICUs PATIENTS: Patients were classified into six groups according to their serum potassium level at admission: three groups of hypokalemia and three groups of hyperkalemia defined as serious hypokalemia [K+] < 2.5 and serious hyperkalemia [K+] > 7 mmol/L, moderate hypokalemia 2.5 ≤ [K+] < 3 mmol/L and moderate hyperkalemia 6 < [K+] ≤ 7 mmol/L, and mild hypokalemia 3 ≤ [K+] < 3.5 mmol/L and mild hyperkalemia 5 < [K+] ≤ 6 mmol/L. We sorted evolution at day 2 of dyskalemia into three categories: balanced, not-balanced, and overbalanced. INTERVENTION: None MEASUREMENTS AND MAIN RESULTS: Of 12,090 patients, 2108 (17.4%) had hypokalemia and 1445 (12%) had hyperkalemia. Prognostic impact of dyskalemia and its correction was assessed using multivariate Cox models. After adjustment, hypokalemia and hyperkalemia were independently associated with a greater risk of 28-day mortality. Mild hyperkalemic patients had the highest mortality (hazard ratio (HR) 1.29, 95% confidence interval (CI) [1.13-1.47], p < 0.001). Adjusted 28-day mortality was higher if serum potassium level was not-balanced at day 2 (aHR = 1.51, 95% CI [1.30-1.76], p < 0.0001) and numerically higher but not significantly different if serum potassium level was overbalanced at day 2 (aHR = 1.157, 95% CI [0.84-1.60], p = 0.38). Occurrence of cardiac events was evaluated by logistic regression. Except for patients with serious hypokalemia at admission, the depth of dyskalemia was associated with increased risk of cardiac events. CONCLUSIONS: Dyskalemia is common at ICU admission and associated with increased mortality. Occurrence of cardiac events increased with dyskalemia depth. A correction of serum potassium level by day 2 was associated with improved prognosis.

Upper gastrointestinal bleeding in adults treated with veno-arterial extracorporeal membrane oxygenation: a cohort study.

OBJECTIVES: Upper gastrointestinal bleeding (UGIB) is a common complication in adults treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock or cardiac arrest. We aimed to determine risk factors, prevalence and outcomes associated with VA-ECMO-associated UGIB in adult patients. METHODS: We conducted a retrospective cohort study (2014-2022) on consecutive VA-ECMO patients in the medical and infectious disease intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France. UGIB was defined as (i) an overt bleeding (haematemesis, melena, haematochezia) or (ii) acute anaemia associated with a lesion diagnosed on upper gastrointestinal endoscopy. VA-ECMO-associated UGIB was defined as an UGIB occurring during VA-ECMO, or up to 10 days after decannulation in patients weaned off extracorporeal membrane oxygenation (ECMO). Cause-specific models were used to identify factors associated with UGIB and death, respectively. RESULTS: Among the 455 patients included, 48 (10%) were diagnosed with UGIB after a median of 12 [7; 23] days following ECMO cannulation. Mortality occurred in 36 (75%) patients with UGIB and 243 (60%) patients without. UGIB patients had longer intensive care unit stays (32 [19; 60] vs 18 [7; 37] days; P < 0.01), longer ECMO (14 [9; 18] vs 7 [4; 11] days; P < 0.01) and mechanical ventilation durations (21 [16; 36] vs 10 [5; 20] days; P < 0.01), as compared to non-UGIB patients. Ninety upper gastrointestinal endoscopies were performed, and the most frequent lesions detected were gastro-duodenal ulcers (n = 23, 26%), leading to 11/90 therapeutic procedures. By multivariable analysis, a history of peptic ulcer [cause-specific hazard ratio (CSHR) 2.93, 95% confidence interval (CI) [1.01; 8.51]], a dual antiplatelet therapy (CSHR 2.0, 95% CI [1.07; 3.72]) and extracorporeal cardiopulmonary resuscitation (CSHR 2.78, 95% CI [1.42; 5.45]) were independently associated with an increased risk of UGIB. CONCLUSIONS: In adult patients under VA-ECMO, a history of gastric ulcer, dual antiplatelet therapy and extracorporeal cardiopulmonary resuscitation were independently associated with an increased risk of UGIB. This study highlights the potential role of acute ischaemia-reperfusion injury in the pathophysiology of VA-ECMO-associated UGIB.

Prolonged cefazolin course for treatment of methicillin susceptible staphylococcus species infections and the impact on the emergence of multidrug-resistant bacteria during cloxacillin shortage.

OBJECTIVES: To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. METHODS: Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. RESULTS: Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. CONCLUSION: Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.

Sepsis and septic shock in France: incidences, outcomes and costs of care.

BACKGROUND: Sepsis is one of the leading causes of death worldwide. The associated incidence, mortality and trends do not differ greatly between documented reports. The purpose of this study was to provide an in-depth description of patients with sepsis and septic shock hospitalized in France from 2010 to 2015 and to explore the temporal trends of their clinical characteristics, costs and outcomes. METHODS: Retrospective cohort study of the French hospital administrative database in which organ failure therapies and severity scores are systematically registered. All patients admitted between 2010 and 2015 for sepsis and septic shock as defined by an ICD-10 code for infection, and for organ failure or the use of organ failure supplementation were included. Incidence, outcomes and trends were analyzed. Subgroup analyses based on several coding strategies and adjusted for severity scores were performed. RESULTS: A total of 737,147 patients with sepsis and 492,902 patients with septic shock were included. From 2010 to 2015, the incidence of sepsis and septic shock increased, respectively, from 206 to 243 and from 135 to 171 cases per 100,000 population. Case fatality remained at 34% for sepsis, but decreased from 46 to 44% for septic shock. Median hospital stay costs amounted to €11,400 (IQR: 5036; 24,364) for patients with sepsis and €16,439 (IQR: 7339; 29,360) for patients with septic shock. After adjustment for case-mix and illness severity, the risk of death was stable for sepsis (0.08% [- 0.04; 0.20] per year), but decreased for sepsis patients admitted to the intensive care unit and for cases of septic shock (- 0.33%[ - 0.40; - 0.27] per year). CONCLUSIONS: Sepsis is common, frequently fatal and expensive to treat. Its incidence has increased. Case fatality has decreased in most severely affected patients, owing partly to general improvements in care.

Factors associated with major adverse kidney events in patients who underwent veno-arterial extracorporeal membrane oxygenation.

OBJECTIVE: To describe acute kidney injury (AKI) natural history and to identify predictors of major adverse kidney events (MAKE) within 1 year in patients supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO). DESIGN: Retrospective observational study. SETTING: Medical French intensive care unit between January 2014 and December 2016. PATIENTS: Consecutive patients implanted with VA-ECMO ≥ 16 years, VA-ECMO for at least ≥ 48 h, and without end-stage chronic kidney disease (CKD). INTERVENTION: None. MEASUREMENTS: Multivariate logistic regression of factors associated with MAKE at 1 year defined as one of the following criteria within day 360: death and receipt of renal replacement therapy (RRT) or persistent renal dysfunction, i.e., CKD ≥ stage 3 corresponding to an estimated glomerular filtration rate (eGFR) ≤ 60 ml/min/1.73 m2 and MAKE at day 30 and day 90 defined as one of the following criteria within day 30 or day 90: death, receipt of renal replacement therapy and serum creatinine ≥ threefold increase. MAIN RESULTS: 158 consecutive patients were included (male sex: 75.9%; median and interquartile range: age: 59 [47-66], Simplified Acute Physiology Score II: 55 [39-66], Sepsis-related Organ Failure Assessment Score: 9 [7-12], time on VA-ECMO: 7.5 [4-12] days). Among them 145 (91.8%) developed an AKI during the intensive care unit (ICU) stay and 85 (53.8%) needed renal replacement therapy (RRT). 59.9% (91/152), 60.5% (89/147) and 85.1% (120/141) evaluable patients had a MAKE-30, MAKE-90 and MAKE-360, respectively. Factors significantly associated with MAKE-360 were eGFR at baseline (odds ratio (OR) 0.98, confidence interval 95% (CI) [0.97;1.00], p 0.02), Kidney Disease Improving Global Outcome (KDIGO) stage at cannulation (p = 0.03), e.g., stage 3 vs. reference stage 0 OR 10.20 [1.77-58.87], and number of red blood cell (RBC) packs received while under ECMO (OR 1.14, CI 95% [1.01;1.28], p = 0.03). At 1 year among the 51 survivors, almost half of the alive patients (n = 20/51) had a decline of estimated glomerular filtration (eGFR) > 30% mL/min/1.73 m2. Their median eGFR decline was - 26.3% [- 46.6;- 10.7]. CONCLUSION: Patients undergoing VA-ECMO had a high risk of AKI during the ICU stay. Factors associated with MAKE 360 were mainly eGFR at baseline, KDIGO stage at cannulation and, number of RBC packs received while under ECMO. Among survivors at 1 year, almost half of the alive patients (n = 20/51) had a decline eGFR > 30%.

Neuron-Specific Enolase Levels in Adults Under Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: We aimed to determine if elevations in serum neuron-specific enolase are associated with brain injury and outcomes in adults who require venoarterial extracorporeal membrane oxygenation. DESIGN: Prospective observational study. SETTING: Two ICUs of a university hospital, Paris, France. PATIENTS: Consecutive adult patients treated with venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock or in-hospital refractory cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum sampled 1, 3, and 7 days after venoarterial extracorporeal membrane oxygenation cannulation was stored at -80°C and neuron-specific enolase concentrations were measured in batches at the end of the study. The association between neuron-specific enolase concentrations and outcomes (28-d mortality and poor outcome, defined by a score of 4-6 on the modified Rankin scale at 90 d) were explored by multivariable logistic regression, with neuron-specific enolase concentrations dichotomized according to median values. One-hundred three patients were included, of whom 26 (25%) received preextracorporeal membrane oxygenation cardiopulmonary resuscitation. Median (interquartile range) day-1, day-3, and day-7 neuron-specific enolase serum concentrations were 37 µg/L (26-51 µg/L), 25 µg/L (19-37) µg/L, and 22 µg/L (17-31 µg/L). After adjustment for Simplified Acute Physiology Score II, preextracorporeal membrane oxygenation cardiopulmonary resuscitation, and Sepsis Organ Failure Assessment score at time of cannulation, a day-3 neuron-specific enolase greater than 25 µg/L remained independently associated with 28-day mortality (adjusted odds ratio, 4.98; 95% CI, 1.86-13.32) and poor outcome at 90 days (adjusted odds ratio, 4.63; 95% CI, 1.81-11.84). A day-3 neuron-specific enolase threshold greater than 80 µg/L had a 100% specificity for prediction of both mortality (95% CI, 92-100%) and poor functional outcome (95% CI, 89-100%). In a subset of patients who underwent brain CT, neuron-specific enolase concentrations were significantly higher in patients diagnosed with stroke, as compared with those without stroke. CONCLUSIONS: In adult patients under venoarterial extracorporeal membrane oxygenation, day-3 serum neuron-specific enolase concentrations are independently associated with short-term mortality and poor functional outcomes. These findings deserve validation in a multicenter setting.

Correction to: Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017.

After publication of the original article [1], we were notified that family names have been exchanged with the first names for all authors. Below the name are tagged correctly.

Changes in the clinical presentation and outcomes of patients treated for severe malaria in a referral French university intensive care unit from 2004 to 2017.

BACKGROUND: In France, the incidence of severe imported malaria cases increased since early 2000. Artesunate was available (temporarily use authorization) since mid-2011 in France and commonly used for severe malaria since early 2013. Thus, the study objectives were to describe the patients with severe imported malaria admitted in intensive care unit (ICU) and assess the changes in clinical presentation and outcomes before and after this date. METHODS: Retrospective observational single-center study in the infectious diseases ICU of a referral university hospital, conducted on patients admitted for severe imported malaria from 2004 to 2017. Demographic variables, severity scores, WHO's severity criteria on admission, treatment, and ICU and hospital lengths of stay were collected. Patients' characteristics and outcomes were compared between both periods. A poor outcome was defined as the composite endpoint of death, or requirement for vasopressors, invasive mechanical ventilation and/or renal replacement therapy. RESULTS: 189 patients were included, 98 in 2004-2012 and 91 in 2013-2017, most often from West and Central African countries (96%). The number of WHO criteria for severe malaria was comparable in both groups, but SAPS II, SOFA and ICU length of stay were significantly higher in 2004-2012, while patients of African origin living in France were less frequent (p < 0.01). The outcome was poor for 41/98 cases in 2004-2012 and 12/91 cases in 2013-2017 (p < 0.01). The risk factors of poor outcome on the multivariate logistic regression were a neurological failure (adjusted odds ratio (adjOR = 3.23; 95% CI (1.03-10.08), p = 0.004), cardio-circulatory failure (adjOR = 9.92; 95% CI (2.34-42), p = <0.01) and creatinine blood levels > 265 µmol/L (adjOR = 10.76; 95% CI (3.17-36.53), p < 0.01). In the multivariate analysis, IV artesunate was not associated with a better outcome. Patients of African origin did not seem to have a better outcome than Caucasian patients or those from other origins (adjOR = 0.59; 95% CI (0.21-1.65), p = 0.31). CONCLUSION: Patients with imported malaria admitted in ICU in 2013-2017 were less severely ill than those in 2004-2012. These trends could be partially explained by the increasing proportion of African patients visiting friends or relatives or living in endemic areas.