Intensive care unit (ICU) survivors have reduced long-term survival compared to the general population. Identifying parameters at ICU discharge that are associated with poor long-term outcomes may prove useful in targeting an at-risk population. The main objective of the study was to identify clinical and biological determinants of death in the year following ICU discharge. FROG-ICU was a prospective, observational, multicenter cohort study of ICU survivors followed 1 year after discharge, including 21 medical, surgical or mixed ICUs in France and Belgium. All consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following ICU admission and discharged from ICU were included. The main outcome measure was all-cause mortality at 1 year after ICU discharge. Clinical and biological parameters on ICU discharge were measured, including the circulating cardiovascular biomarkers N-terminal pro-B type natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and soluble-ST2. Socioeconomic status was assessed using a validated deprivation index (FDep). Of 1570 patients discharged alive from the ICU, 333 (21%) died over the following year. Multivariable analysis identified age, comorbidity, red blood cell transfusion, ICU length of stay and abnormalities in common clinical factors at the time of ICU discharge (low systolic blood pressure, temperature, total protein, platelet and white cell count) as independent factors associated with 1-year mortality. Elevated biomarkers of cardiac and vascular failure independently associated with 1-year death when they are added to multivariable model, with an almost 3-fold increase in the risk of death when combined (adjusted odds ratio 2.84 (95% confidence interval 1.73–4.65), p < 0.001). The FROG-ICU study identified, at the time of ICU discharge, potentially actionable clinical and biological factors associated with poor long-term outcome after ICU discharge. Those factors may guide discharge planning and directed interventions. ClinicalTrials.gov NCT01367093 . Registered on 6 June 2011.

Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5–148.1 pg/ml]. Initial SOFA score was 7 [IQR 5–10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9–2.9]; adjusted HR 1.6 [CI 1.1–2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5–9.8). AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. ClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015.

Atrial fibrillation (AFib) is associated with adverse outcome in critical illness, but whether this effect is independent from other risk factors remains uncertain. New-onset AFib during critical illness may be independently associated with increased in-hospital and long-term risk of death. FROG-ICU was a prospective, observational, multi-centre cohort study designed to investigate the outcome of critically ill patients. Inclusion criteria were invasive mechanical ventilation and/or treatment with a positive inotropic agent for >24 h. Heart rhythm was assessed at inclusion and during ICU stay with digital ECG recordings. Among patients who had AFib during ICU stay, new-onset and recurrent AFib were diagnosed in patients without and with previous history of AFib, respectively. Primary endpoint was in-hospital mortality; secondary endpoint was 1-year mortality among ICU survivors. The study included 1841 critically ill patients. During ICU stay, AFib occurred in 343 patients (19%). New-onset AFib (n = 212) had higher in-hospital mortality compared to no AFib (47 vs. 23%, P < 0.001) or recurrent AFib (34%, P = 0.032). New-onset AFib showed increased risk of in-hospital death after multivariable adjustment compared to no AFib (OR 1.6, P = 0.003) or recurrent AFib (OR 1.8, P = 0.02). Among the 1464 ICU-survivors, new-onset AFib during ICU stay showed higher post-ICU risk of death compared to no AFib (HR 2.2, P < 0.001). After multivariable adjustment, new-onset AFib showed higher post-ICU risk of death compared to no AFib (HR 1.6, P = 0.03). New-onset AFib is independently associated with in-hospital and post-ICU risk of death in critically ill patients.

Over the recent period, the use of induced hypothermia has gained an increasing interest for critically ill patients, in particular in brain-injured patients. The term “targeted temperature management” (TTM) has now emerged as the most appropriate when referring to interventions used to reach and maintain a specific level temperature for each individual. TTM may be used to prevent fever, to maintain normothermia, or to lower core temperature. This treatment is widely used in intensive care units, mostly as a primary neuroprotective method. Indications are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of TTM in adult and paediatric critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Société de Réanimation de Langue Française [SRLF]) and the French Society of Anesthesia and Intensive Care Medicine (Société Francaise d’Anesthésie Réanimation [SFAR]) with the participation of the French Emergency Medicine Association (Société Française de Médecine d’Urgence [SFMU]), the French Group for Pediatric Intensive Care and Emergencies (Groupe Francophone de Réanimation et Urgences Pédiatriques [GFRUP]), the French National Association of Neuro-Anesthesiology and Critical Care (Association Nationale de Neuro-Anesthésie Réanimation Française [ANARLF]), and the French Neurovascular Society (Société Française Neurovasculaire [SFNV]). Fifteen experts and two coordinators agreed to consider questions concerning TTM and its practical implementation in five clinical situations: cardiac arrest, traumatic brain injury, stroke, other brain injuries, and shock. This resulted in 30 recommendations: 3 recommendations were strong (Grade 1), 13 were weak (Grade 2), and 14 were experts’ opinions. After two rounds of rating and various amendments, a strong agreement from voting participants was obtained for all 30 (100%) recommendations, which are exposed in the present article.

Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75–0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62–1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).