Argon attenuates multiorgan failure following experimental aortic cross-clamping.

AIMS: Argon has been shown to prevent ischaemic injuries in several scenarios of regional ischaemia. We determined whether it could provide a systemic effect in a model of multiorgan failure (MOF) induced by aortic cross-clamping. METHODS: Anaesthetized rabbits were submitted to aortic cross-clamping (30 min) and subsequent reperfusion (300 min). They were either ventilated with oxygen-enriched air throughout the protocol [fraction of inspired oxygen (FiO2 ) = 30%; control group) or with a mixture of 30% oxygen and 70% argon (argon groups). In a first group treated with argon ('Argon-Total'), its administration was started 30 min before ischaemia and maintained throughout the protocol. In the two other groups, the administration was started either 30 min before ischaemia ('Argon-Pre') or at the onset of reperfusion ('Argon-Post'), for a total duration of 2 h. Cardiovascular, renal and inflammatory endpoints were assessed throughout protocol. RESULTS: Compared with control, shock was significantly attenuated in Argon-Total and Argon-Pre but not Argon-Post groups (e.g. cardiac output = 62±5 vs. 29 ± 5 ml min-1 kg-1 in Argon-Total and control groups at the end of the follow-up). Shock and renal failure were reduced in all argon vs. control groups. Histopathological examination of the gut showed attenuation of ischaemic lesions in all argon vs. control groups. Blood transcription levels of interleukin (IL) 1ß, IL-8, IL-10 and hypoxia-inducible factor 1α were not significantly different between groups. CONCLUSION: Argon attenuated clinical and biological modifications of cardiovascular, renal and intestinal systems, but not the inflammatory response, after aortic cross-clamping. The window of administration was crucial to optimize organ protection.

A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. METHODS: We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. RESULTS: Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70-0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50-86], specificity of 85% [55-98], a negative predictive value of 58% [36-93] and a positive predictive value 90% [67-96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12-0.75], p = 0.01). CONCLUSION: In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.

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.

Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients.

BACKGROUND: Deep sedation may hamper the detection of neurological deterioration in brain-injured patients. Impaired brainstem reflexes within the first 24 h of deep sedation are associated with increased mortality in non-brain-injured patients. Our objective was to confirm this association in brain-injured patients. METHODS: This was an observational prospective multicenter cohort study involving four neuro-intensive care units. We included acute brain-injured patients requiring deep sedation, defined by a Richmond Assessment Sedation Scale (RASS) < -3. Neurological assessment was performed at day 1 and included pupillary diameter, pupillary light, corneal and cough reflexes, and grimace and motor response to noxious stimuli. Pre-sedation Glasgow Coma Scale (GCS) and Simplified Acute Physiology Score (SAPS-II) were collected, as well as the cause of death in the Intensive Care Unit (ICU). RESULTS: A total of 137 brain-injured patients were recruited, including 70 (51%) traumatic brain-injured patients, 40 (29%) vascular (subarachnoid hemorrhage or intracerebral hemorrhage). Thirty patients (22%) died in the ICU. At day 1, the corneal (OR 2.69, p = 0.034) and cough reflexes (OR 5.12, p = 0.0003) were more frequently abolished in patients that died in the ICU. In a multivariate analysis, abolished cough reflex was associated with ICU mortality after adjustment to pre-sedation GCS, SAPS-II, RASS (OR: 5.19, 95% CI [1.92-14.1], p = 0.001) or dose of sedatives (OR: 8.89, 95% CI [2.64-30.0], p = 0.0004). CONCLUSION: Early (day 1) cough reflex abolition is an independent predictor of mortality in deeply sedated brain-injured patients. Abolished cough reflex likely reflects a brainstem dysfunction that might result from the combination of primary and secondary neuro-inflammatory cerebral insults revealed and/or worsened by sedation.

Prognostic value of adrenal gland volume after cardiac arrest: Association of CT-scan evaluation with shock and mortality.

BACKGROUND: Adrenal gland volume is associated with survival in septic shock. As sepsis and post-cardiac arrest syndrome share many pathophysiological features, we assessed the association between adrenal gland volume measured by computerized tomography (CT)-scan and post-cardiac arrest shock and intensive care unit (ICU) mortality, in a large cohort of out-of-hospital cardiac arrest (OHCA) patients. We also investigated the association between adrenal hormonal function and both adrenal gland volume and outcomes. PATIENTS AND METHODS: Prospective analysis of CT-scan performed at hospital admission in patients admitted after OHCA (2007-2012). A pair of blinded radiologist calculated manually adrenal gland volume. In a subgroup of patients, plasma cortisol was measured at admission and 60 min after a cosyntropin test. Factors associated with post-cardiac arrest shock and ICU mortality were identified using multivariate logistic regression. RESULTS: Among 775 patients admitted during this period after OHCA, 138 patients were included: 72 patients (52.2%) developed a post-cardiac arrest shock, and 98 patients (71.1%) died. In univariate analysis, adrenal gland volume was not different between patients with and without post-cardiac arrest shock: 10.6 and 11.3 cm3, respectively (p = 0.9) and between patients discharged alive or dead: 10.2 and 11.8 cm3, respectively (p = 0.4). Multivariate analysis confirmed that total adrenal gland volume was associated neither with post-cardiac arrest shock nor mortality. Neither baseline cortisol level nor delta between baseline and after cosyntropin test cortisol levels were associated with adrenal volume, post-cardiac arrest shock onset or mortality. CONCLUSION: After OHCA, adrenal gland volume is not associated with post-cardiac arrest shock onset or ICU mortality. Adrenal gland volume does not predict adrenal gland hormonal response.

Influence of body mass index on the prognosis of patients successfully resuscitated from out-of-hospital cardiac arrest treated by therapeutic hypothermia.

BACKGROUND: Obesity prevalence has dramatically increased over recent years and is associated with cardiovascular diseases, but data are lacking on its prognostic impact in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Data of all consecutive OHCA patients admitted in two cardiac arrest centers from Paris and suburbs between 2005 and 2012 were prospectively collected. Patients treated by therapeutic hypothermia (TH) were included in the analysis. Logistic and Cox regression analyses were used to quantify the association between body mass index (BMI) at hospital admission and day-30 and 1-year mortality respectively. RESULTS: 818 patients were included in the study (median age 60.9 [50.8-72.7] year, 70.2% male). Obese patients (BMI>30kgm-2) were older, more frequently male and evidenced more frequently cardiovascular risk factors than normally (18.530kgm-2 was independently associated with day-30 mortality (Odds ratio [OR] in comparison with normally weight patients 2.45; 95% confidence interval [95%CI: 1.32-4.56; p<0.01]). Obesity was not associated with one-year mortality (Hazard ratio [HR] 0.99, 95%CI 0.21,4.67; p=0.99) while underweight was associated with one-year mortality in this subgroup of patients (Hazard ratio [HR] 3.94, 95%CI 1.11,14.01; p=0.03). CONCLUSION: In the present study, obesity was independently associated with day-30 mortality in successfully resuscitated ICU TH OHCA patients. Further studies are needed to understand the mechanisms that underpin this finding.