Association of Lack of Fear of Dying With New Organ Failure: Results of a Multicenter Prospective Cohort Study.

BACKGROUND: Patients' anxiety on intensive care unit (ICU) admission is associated with subsequent deterioration. OBJECTIVE: To assess whether patients' fears/anxiety are predictive of new organ failure within 7 days of ICU admission. METHODS: In a prospective 3-center cohort study of non-comatose patients without delirium or invasive mechanical ventilation, 9 specific fears were evaluated through yes/no questions. Illness severity was assessed using the Simplified Acute Physiology Score II (SAPS II) and the Sequential Organ Failure Assessment (SOFA). Intensity of acute and chronic anxiety was assessed with the state and trait components of the State-Trait Anxiety Inventory (STAI). Patients were followed up for 7 days. RESULTS: From April 2014 to December 2017, 373 patients (median [IQR] age, 63 [48-74] years; 152 [40.8%] women; median (IQR) SAPS II, 27 [19-37]) were included. Feelings of vulnerability and fear of dying were reported by 203 (54.4%) and 172 (46.1%) patients, respectively. The STAI-State score was 40 or greater in 192 patients (51.5%). Ninety-four patients (25.2%) had new organ failure. Feelings of vulnerability (odds ratio, 1.96 [95% CI, 1.12-3.43]; P=.02) and absence of fear of dying (odds ratio, 2.38 [95% CI, 1.37-4.17]; P=.002) were associated with new organ failure after adjustment for STAI-State score (≥40), SAPS II, and SOFA score. CONCLUSION: Absence of fear of dying is associated with new organ failure within the first 7 days after ICU admission. Fear of dying may protect against subsequent deterioration by mobilizing patients' homeostatic resources. ClinicalTrials.gov Identifier: NCT02355626.

Association Between Anxiety and New Organ Failure, Independently of Critical Illness Severity and Respiratory Status: A Prospective Multicentric Cohort Study.

OBJECTIVES: Anxiety results from the anticipation of a threat and might be associated with poor outcome in the critically ill. This study aims at showing that anxiety at admission in critically ill patients is associated with new organ failure over the first 7 days of ICU hospitalization independently of baseline organ failure at admission. DESIGN: Prospective multicenter cohort study. SETTING: Three mixed ICU from April 2014 to December 2017. PATIENTS: Coma-, delirium-, and invasive mechanical ventilation-free patients admitted to the ICU were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: "State anxiety" was assessed using the state component of the State-Trait Anxiety Inventory State. Severity of illness was measured using Simplified Acute Physiology Score II and Sequential Organ Failure Assessment scores. Primary endpoint was a composite of occurrence of death or new organ failure in the first 7 days after admission. Three hundred ninety-one patients were included; 159 of 391 women (40.7%); median age 63 years (49-74 yr); median Simplified Acute Physiology Score II 28 (19-37). Two hundred three out of 391 patients (51.9%) reported moderate to severe anxiety (State-Trait Anxiety Inventory State ≥ 40). One hundred two out of 391 patients (26.1%) developed a new organ failure. After adjustment to Simplified Acute Physiology Score II and Sequential Organ Failure Assessment, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with the primary endpoint (odds ratio, 1.94; 95% CI, 1.18-3.18; p = 0.009) and respiratory failure. In post hoc analysis, State-Trait Anxiety Inventory State greater than or equal to 40 was associated with new organ failure independently and notably of respiratory status at admission (dyspnea-Visual Analogic Scale and PaCO2 ≥ 45 mm Hg). CONCLUSIONS: Moderate to severe anxiety at ICU admission is associated with early occurrence of new organ failure in critically ill patients, independently of respiratory status and severity of critical illness. The causality link could be addressed in an interventional trial.

Choosing appropriate size of I-Gel® for initial success insertion: a prospective comparative study.

PURPOSE: The optimal size of the I-Gel® remains unclear since the manufacturer's weight-based formula (size 3 for weight < 50 kg, size 4 for weight 50-90 kg, and size 5 for weight > 90 kg) for the laryngeal mask airway I-Gel® is not evidence-based. We hypothesised that sex may also guide the choice of I-Gel® size. METHODS: Insertion success rates of the I-Gel® chosen according to the weight-based formula were prospectively recorded and compared with those of a patients' cohort ventilated with an I-Gel® chosen according to the sex-based formula recorded. Two periods of 18 months were randomised in three independent hospitals in France to study each choice strategy. Patients requiring I-Gel® size change were compared with those who where successfully ventilated with the initially chosen device. Complications linked to the I-Gel® and factors for changing the size of the I-Gel® were also recorded and analysed. RESULTS: Data from 900 patients were prospectively collected in the three participating centres. The overall initial ventilation was inadequate in 80 cases, including 7% (n = 31) in the weight-based group and 3% (n = 13) in the sex-based group (P = 0.01). In the weight-based group, changing size of I-Gel® was successful in 28 (90%) cases. In the sex-based group, changing size of I-Gel® was useful in 1 case only. Endotracheal tube insertion was necessary in 15 cases despite changing I-Gel® size, including 3 cases in the weight-based group and 12 cases in the sex-based group. Ease of insertion and postoperative pharyngo-laryngeal problems were similar between groups with or without changing size of I-Gel®. CONCLUSION: Adequate ventilation is achieved most of the time using size selection for the I-Gel® laryngeal mask airway according to the manufacturer's weight-based formula. However, our results suggest that the sex-based formula in healthy, anaesthetised, adult patients may also be appropriate for I-Gel® size choice.

Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study.

AIMS: Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. METHODS AND RESULTS: This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. CONCLUSION: A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.

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.

Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality.

BACKGROUND AND PURPOSE: Deep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients. METHODS: Observational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A "Brainstem Responses Assessment Sedation Score" (BRASS) was generated. RESULTS: Two distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80] respectively). CONCLUSION: In this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.

Acute kidney injury after out-of-hospital cardiac arrest: risk factors and prognosis in a large cohort.

PURPOSE: Characteristics of acute kidney injury (AKI) occurring after out-of-hospital cardiac arrest (OHCA) are incompletely described. We aimed to evaluate the prevalence of AKI, identifying risk factors and assessing the impact of AKI on outcome after OHCA. METHODS: Single-center study between 2007 and 2012 in a cardiac arrest center in Paris, France. All consecutive OHCA patients with at least one weight measurement and one serum creatinine level available and treated by therapeutic hypothermia were included, except those with chronic kidney disease and those dead on arrival. AKI was defined as stage 3 of the Acute Kidney Injury Network (AKIN) classification. Main outcome was day-30 mortality. Factors associated with AKI occurrence and day-30 mortality were evaluated by logistic regression. RESULTS: 580 patients (71.3% male, median age 59.3 years, initial shockable rhythm in 56.9% of cases) were included in the analysis. AKI stage 3 occurred in 280 (48.3%) patients. Age, male gender, resuscitation duration, post-resuscitation shock, public setting, and initial rhythm were associated with AKI stage 3. AKI stage 3 was associated with a significantly higher day-30 mortality rate [OR 1.60; 95% CI (1.05, 2.43); p = 0.03]. No independent association between AKI and neurologic outcome was observed. At day 30, 67 patients had a normal kidney function (eGFR >75 mL/min/1.73 m(2)), and five remained dialysis-dependent. Patients with eGFR higher than 75 mL/min/1.73 m(2) at day 30 were younger and more frequently male. CONCLUSION: AKI stage 3 was frequent after OHCA and was associated with poorer outcome. Improvement strategies in post-resuscitation care should consider AKI as a potential target of treatment.

Jugular versus femoral short-term catheterization and risk of infection in intensive care unit patients. Causal analysis of two randomized trials.

RATIONALE: When subclavian access is not possible, controversy exists between the internal jugular and femoral sites for the choice of central-venous access in intensive care unit patients. OBJECTIVES: To compare infection and colonization rates of short-term jugular and femoral catheters. METHODS: Using data from two multicenter studies, we compared femoral and internal jugular for the risks of catheter-related bloodstream infection, major catheter-related infection, and catheter-tip colonization. We also compared the rates of dressing disruption and skin colonization. We used marginal structural models with inverse probability of treatment weighting to adjust on indication bias. MEASUREMENTS AND MAIN RESULTS: We included 2,128 patients (2,527 catheters and 19,481 catheter-days). We found no difference in catheter-related bloodstream infection (internal jugular 1.0 vs. femoral 1.1 per 1,000 catheter-days; hazard ratio [HR], 0.63 [0.25-1.63]; P = 0.34), major catheter-related infection (internal jugular 1.8 vs. femoral 1.4 per 1,000 catheter-days; HR, 0.91 [0.38-2.18]; P = 0.34), and colonization (internal jugular 11.6 vs. femoral 12.9 per 1,000 catheter-days; HR, 0.80 [0.25-1.63]; P = 0.15). However, colonization was higher with femoral for female (HR, 0.39 [0.24-0.63]; P < 0.001) and, at the significance limit, catheter maintained for more than 4 days (HR, 0.73 [0.53-1.01]; P = 0.05). The absence of benefit of internal jugular before Day 5 was related to a higher skin colonization at the internal jugular site for catheters removed before Day 5. After the fourth day, dressing disruption became more frequent with femoral catheters and may explain the subsequent risk of catheter colonization. Differences in cutaneous and catheter colonization between internal jugular and femoral was suppressed by the use of chlorhexidine-impregnated dressings. CONCLUSIONS: Femoral and internal jugular accesses lead to similar risks of catheter infection. Internal jugular might be preferred for female, nonchlorhexidine-impregnated dressings users, and when catheters are left in place more than 4 days. Both sites are acceptable when a subclavian approach is not feasible. Clinical trial registered with www.clinicaltrials.gov (NCT00417235 and NCT01189682).

Decompression sickness in urban divers in France.

BACKGROUND: Decompression sickness (DCS) can occur in SCUBA divers. DCS is treated with oxygen, preferably given under hyperbaric conditions. Although Paris (France) is located at a distance from the sea or lakes, some injured divers require hyperbaric oxygen treatment (HBOT) in this city, sometimes within a specific time frame. Thus, this study investigated the epidemiology and outcomes of such urban divers. AIM: We conducted an observational study of SCUBA divers admitted to the Raymond Poincaré Hyperbaric centre near Paris from 1993 to 2003. MATERIALS AND METHODS: We prospectively enrolled 69 consecutive SCUBA divers presenting DCS. Common risk factors were reported, especially aeroplane flight and training dives. Symptoms are very often atypical (63%) and onset time of symptoms is often too long (59% after 2 h) due to denial of symptoms. First aid is generally inadequate, with only 23% of victims receiving oxygen, fluid loading and aspirin together. HBOT was given for 42 (61%) patients although their examination results were considered as normal. CONCLUSIONS: Diving pits and diving travel agencies should do more to warn divers of the need for treatment with normobaric oxygen and hydration pending HBOT. Moreover, hyperbaric physicians should better clarify HBOT indications for both symptoms of late onset and atypical presentations.

Randomized controlled trial of chlorhexidine dressing and highly adhesive dressing for preventing catheter-related infections in critically ill adults.

RATIONALE: Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. OBJECTIVES: To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. METHODS: In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. MEASUREMENTS AND MAIN RESULTS: A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. CONCLUSIONS: A large randomized trial demonstrated that chlorhexidine-gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials.gov (NCT 01189682).

Relevance of anxiety in clinical practice of Guillain-Barre syndrome: a cohort study.

OBJECTIVES: Illness is often associated with anxiety, but few data exist about the prognostic significance of this phenomenon. To address this issue, we assessed whether patient anxiety is associated with subsequent need for intubation in Guillain-Barré syndrome (GBS). DESIGN: Incident case-cohort study. SETTING: Acute secondary care in a teaching hospital (France) from 2006 to 2010. PARTICIPANTS: 110 adult GBS patients. Either language barrier or cognitive decline that precluded understanding was considered as exclusion criteria. PRIMARY OUTCOME: Acute respiratory failure. INTERVENTIONS: At admission, anxiety and clinical factors (including known predictors of respiratory failure: delay between GBS onset and admission, inability to lift head, vital capacity (VC)) were assessed and related to subsequent need for mechanical ventilation (MV). Anxiety was assessed using a Visual Analogical Scale (VAS), the State Anxiety Inventory form Y1 (STAI-Y1) score and a novel-specific questionnaire, evaluating fears potentially triggered by GBS. Patients were asked to choose which they found most stressful from weakness, pain, breathlessness and uncertainty. RESULTS: 23 (22%) were subsequently ventilated. Mean STAI-Y1 was 47.2 (range 22-77) and anxiety VAS 5.2 (range 0-10). STAI was above 60/80 in 22 (21%) patients and anxiety VAS above 7/10 in 28 (27%) patients. Fear of remaining paralysed, uncertainty as to how the disease would progress and fear of intubation were the most stressful. Factors significantly associated with anxiety were weakness and bulbar dysfunction. STAI-Y1 was higher and uncertainty more frequent in subsequently ventilated patients, who had shorter onset-admission delay and greater weakness but not a lower VC. Uncertainty was independently associated with subsequent MV. CONCLUSIONS: Early management of patients with GBS should evaluate anxiety and assess its causes both to adjust psychological support and to anticipate subsequent deterioration.

Combined loss of cRel/p50 subunits of NF-κB leads to impaired innate host response in sepsis.

NF-κB, which comprises homo- and hetero-dimers of the five members of the Rel family, plays a crucial role in immunity to infection. The cRel and p50 subunits have been implicated in the development and function of the immune cells, but their in vivo importance remains poorly explored in sepsis. We aimed to study the impact of the combined loss of these two subunits on the innate response to infection in a cecal ligation and puncture model of sepsis. We have explored the possible defects in host defense, including pathogen clearance, bacterial phagocytosis and cytokine plasma release. We also performed gene profiling of cRel(-/-)p50(-/-) and wild-type LPS-stimulated peritoneal macrophages. Deficiency of cRel and p50 led to enhanced mortality to sepsis that was associated with defective macrophages phagocytosis, decreased bacterial clearance and moderate cytokine response. Transcription profile analysis revealed a common inflammatory response but a significant down-regulated transcription of genes encoding for pathogen recognition receptors and antimicrobial molecules, supporting the in vivo findings in mice. In conclusion, the cRel and p50 subunits of NF-κB play an important combined role in the innate response and are crucial for survival and pathogen clearance in polymicrobial sepsis.

Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic.

PURPOSE: To analyze the hurdles in implementing a randomized trial of corticosteroids for severe 2009 H1N1 influenza infections. METHODS: This was an investigator-led, multicenter, randomized, placebo-controlled, double-blind trial of corticosteroids in ICU patients with 2009 H1N1 influenza pneumonia requiring mechanical ventilation. The feasibility of and hurdles in designing and initiating a phase III trial in a short-lived pandemic crisis were analyzed. The regulatory agency and ethics committee approved the study's scientific, financial, and ethical aspects within 4 weeks. Hydrocortisone and placebo were prepared centrally and shipped to participating hospitals within 6 weeks. The inclusion period started on November 9, 2009. RESULTS: From August 1, 2009 to March 8, 2010, only 205/224 ICU patients with H1N1 infections required mechanical ventilation. The peak of the wave was missed by 2-3 weeks and only 26 patients were randomized. The two main reasons for non-inclusion were patients' admission before the beginning of the trial and ICU personnel overwhelmed by clinical duties. Parallel rather than sequential regulatory and ethics approval, and preparation and masking of study drugs by local pharmacists would have allowed the study to start 1 month earlier and before the peak of the "flu" wave. A dedicated research team in each participating center would have increased the ratio of screened to randomized patients. CONCLUSION: This report highlights the main hurdles in implementing a randomized trial for a pandemic critical illness and proposes solutions for future trials.