Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19.

Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d-1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.

The white test for intraoperative screening of bile leakage: a potential trigger factor for acute pancreatitis after liver resection-a case series.

BACKGROUND: Acute pancreatitis after liver resection is a rare but serious complication, and few cases have been described in the literature. Extended lymphadenectomy, and long ischemia due to the Pringle maneuver could be responsible of post-liver resection acute pancreatitis, but the exact causes of AP after hepatectomy remain unclear. CASES PRESENTATION: We report here three cases of AP after hepatectomy and we strongly hypothesize that this is due to the bile leakage white test. 502 hepatectomy were performed at our center and 3 patients (0.6%) experienced acute pancreatitis after LR and all of these three patients underwent the white test at the end of the liver resection. None underwent additionally lymphadenectomy to the liver resection. All patient had a white-test during the liver surgery. We identified distal implantation of the cystic duct in these three patients as a potential cause for acute pancreatitis. CONCLUSION: The white test is useful for detection of bile leakage after liver resection, but we do not recommend a systematic use after LR, because severe acute pancreatitis can be lethal for the patient, especially in case of distal cystic implantation which may facilitate reflux in the main pancreatic duct.

Two-dimensional-strain echocardiography in intensive care unit patients: A prospective, observational study.

PURPOSE: Two-dimensional-strain echocardiography (2D-strain) is a promising technique for the early detection of myocardial dysfunction. Our study was aimed to assess its feasibility in the intensive care unit (ICU). Our secondary goal was to determine if 2D-strain could predict the patient's outcome. METHODS: Conventional echocardiography and 2D-strain were performed on 64 consecutive patients admitted to our ICU. Using 2D-strain, the longitudinal deformation of the left ventricle was assessed. Feasibility of 2D-strain, diagnosis performance, and 28-day mortality prediction were determined. RESULTS: 2D-strain measurements could be performed in 77% of our patients. All 2D-strain variables related to ventricular performance were significantly impaired in the patients who died compared with those who survived. Strain global medium was the only independent echocardiographic variable predictor of 28-day mortality rate (odds ratio 0.60; 95% confidence interval 0.43-0.80, p = 0.002). CONCLUSIONS: 2D-strain measurement is feasible in ICU patients, enabling identifying early left ventricle dysfunction. Strain global medium is an independent predictor of 28-day mortality. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:368-374, 2016.

Sleep disorders among French anaesthesiologists and intensivists working in public hospitals: a self-reported electronic survey.

BACKGROUND: Sleep disorders can affect the health of physicians and patient outcomes. OBJECTIVES: To determine the prevalence of sleep disorders among French anaesthesiologists and intensivists working in a public hospital. DESIGN: A cross-sectional survey. SETTING: Anaesthesiologists and intensivists working in French public hospitals. MAIN OUTCOME MEASURES: Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) was used to assess the degree of excessive daytime sleepiness. RESULTS: Among 1504 responders, 677 (45%) physicians reported sleep disorders. The independent factors associated with sleep disorders were reporting of sleep disorders [odds ratio (OR) 12.04, 95% CI (95% confidence interval) 8.89 to 16.46], sleep time less than 7 h (OR 8.86, 95% CI 6.50 to 12.20), work stress (OR 2.04, 95% CI 1.49 to 2.83), stress at home (OR 1.77, 95% CI 1.24 to 2.53), anxiolytic use (OR 3.69, 95% CI 2.23 to 6.25), psychotropic drug use (OR 3.91, 95% CI 1.51 to 11.52) and excessive daytime sleepiness (OR 1.81, 95% CI 1.34 to 2.45). Six hundred and seventy-six (44%) responders reported excessive daytime sleepiness during their professional activity. The independent factors associated with excessive daytime sleepiness were female sex (OR 1.86, 95% CI 1.49 to 2.34), tea consumption (OR 1.47, 95% CI 1.14 to 1.91), regular practice of nap (OR 1.68, 95% CI 1.34 to 2.09), stress at home (OR 1.31, 95% CI 1.02 to 1.68), more than four extended work shifts monthly (OR 1.25, 95% CI 1.01 to 1.56) and sleep disorders (OR 1.73, 95% CI 1.31 to 2.29). Reporting sleep disorder duration and a sleep time less than 7 h were the two major risk factors for sleep disorders. Female sex was the major risk factor for excessive daytime sleepiness. CONCLUSION: French anaesthesiologists did not report more sleep disorders than the general population, but their alertness is impaired by a factor of two.

Impact of Hyperoxia after Graft Reperfusion on Lactate Level and Outcomes in Adults Undergoing Orthotopic Liver Transplantation.

BACKGROUND: Hyperoxia is common during liver transplantation (LT), without being supported by any guidelines. Recent studies have shown the potential deleterious effect of hyperoxia in similar models of ischemia-reperfusion. Hyperoxia after graft reperfusion during orthotopic LT could increase lactate levels and worsen patient outcomes. METHODS: We conducted a retrospective and monocentric pilot study. All adult patients who underwent LT from 26 July 2013 to 26 December 2017 were considered for inclusion. Patients were classified into two groups according to oxygen levels before graft reperfusion: the hyperoxic group (PaO2 > 200 mmHg) and the nonhyperoxic group (PaO2 < 200 mmHg). The primary endpoint was arterial lactatemia 15 min after graft revascularization. Secondary endpoints included postoperative clinical outcomes and laboratory data. RESULTS: A total of 222 liver transplant recipients were included. Arterial lactatemia after graft revascularization was significantly higher in the hyperoxic group (6.03 ± 4 mmol/L) than in the nonhyperoxic group (4.81 ± 2 mmol/L), p < 0.01. The postoperative hepatic cytolysis peak, duration of mechanical ventilation and duration of ileus were significantly increased in the hyperoxic group. CONCLUSIONS: In the hyperoxic group, the arterial lactatemia, the hepatic cytolysis peak, the mechanical ventilation and the postoperative ileus were higher than in the nonhyperoxic group, suggesting that hyperoxia worsens short-term outcomes and could lead to increase ischemia-reperfusion injury after liver transplantation. A multicenter prospective study should be performed to confirm these results.

Hypoxia-inducible factor (HIF1α) gene expression in human shock states.

INTRODUCTION: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1α as a prognosis marker in patients with shock. METHODS: 50 consecutive adult patients with shock and 11 healthy volunteers were prospectively included. RNA was extracted from whole blood samples and expression of HIF1α was assessed over the first 4 hours of shock. The primary objective was to assess HIF1α as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1α as a diagnostic and follow-up marker. Patient survival was evaluated at day 28. RESULTS: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). The HIF1α expression was significantly higher in the shock patients than in the healthy volunteers (121 [72-168] vs. 48 [38-54] normalized copies, p < 0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 [range 84-183] vs. 121 [range 72-185] normalized copies, p = 0.92), and did not significantly change within the study period. CONCLUSIONS: The present study is the first to demonstrate the increased expression of HIF1α in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock.

Peri-operative risk factors of chronic kidney disease after liver transplantation.

BACKGROUND: Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases. METHODS: All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline. RESULTS: Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35 months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal function at one year: figures were 62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5 days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24 h ≥ 2.5 mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need for post-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score ≥ 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019. CONCLUSIONS: The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures.

Monitoring of plasma creatinine and urinary γ-glutamyl transpeptidase improves detection of acute kidney injury by more than 20%.

OBJECTIVES: We sought to determine how early we can detect acute kidney injury inpatients at intensive care unit admission by combining the use of plasma creatinine and urinary γ-glutamyl transpeptidase. DESIGN: Prospective study including development (n = 100) and validation (n = 56) cohorts. SETTINGS: Intensive care unit of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To determine acute kidney injury, we subtracted measured creatinine clearance from theoretical creatinine clearance with a 25% reduction signifying acute kidney injury. Its incidence in 100 consecutive patients was 36%. An indexed urinary γ-glutamyl transpeptidase-to-urinary creatinine ratio was significantly increased in the patients with acute kidney injury and did not correlate with plasma creatinine (p = .3). Using a predefined threshold of indexed urinary γ-glutamyl transpeptidase-to-urinary creatinine ratio (>12.4 units/mmol) and plasma creatinine (>89 µmol/L), acute kidney injury detection was significantly improved, making it possible to detect 22 (22%) additional patients with acute kidney injury. This finding was confirmed in the validation group. The rates of false-positive results were 30% and 19% in the data development and internal validation cohorts, respectively. CONCLUSIONS: The use of low-cost, widely available markers (creatinine and urinary γ-glutamyl transpeptidase) increases the detection of acute kidney injury. Further studies are needed to determine the impact on outcome with the use of these biomarkers.

Acute severe hepatitis in adult-onset Still's disease: case report and comprehensive review of a life-threatening manifestation.

Acute severe hepatitis is a rare complication of adult-onset Still's disease (AOSD). This condition is poorly characterized. We performed a review of the medical literature to describe clinical, biological, pathological, and treatment characteristics from AOSD patients with acute severe hepatitis. Their characteristics were compared with AOSD patients without severe hepatitis. Twenty-one cases were collected including a new case reported here. Patients with severe hepatitis were mostly young adults with a median age of 28 years (range: 20 to 55 years). Overall, patients with severe hepatitis had less arthritis, macular rash, sore throat, lymphadenopathy, or splenomegaly than patients without severe hepatitis. Cytopenia was more frequent in case of severe hepatitis. Most patients were treated with steroids, and the use of biotherapies has increased over the last decade. Despite treatment, 49% of patients required liver transplantation and 24% died. Key Points • Acute severe hepatitis in adult-onset Still's disease (AOSD) is associated with liver transplantation and/or death in, respectively, 43% and 24% of cases. • Severe hepatitis is the inaugural manifestation of AOSD in half of cases. Diagnosis is difficult when extra-hepatic clinical manifestations are lacking. • The mechanism of hepatic necrosis in AOSD with severe hepatitis is unknown. Liver biopsy is not specific and should not delay treatment initiation.

Factors Associated with 90-Day Mortality in Invasively Ventilated Patients with COVID-19 in Marseille, France.

OBJECTIVES: To describe clinical characteristics and management of intensive care units (ICU) patients with laboratory-confirmed COVID-19 and to determine 90-day mortality after ICU admission and associated risk factors. METHODS: This observational retrospective study was conducted in six intensive care units (ICUs) in three university hospitals in Marseille, France. Between 10 March and 10 May 2020, all adult patients admitted in ICU with laboratory-confirmed SARS-CoV-2 and respiratory failure were eligible for inclusion. The statistical analysis was focused on the mechanically ventilated patients. The primary outcome was the 90-day mortality after ICU admission. RESULTS: Included in the study were 172 patients with COVID-19 related respiratory failure, 117 of whom (67%) received invasive mechanical ventilation. 90-day mortality of the invasively ventilated patients was 27.4%. Median duration of ventilation and median length of stay in ICU for these patients were 20 (9-33) days and 29 (17-46) days. Mortality increased with the severity of ARDS at ICU admission. After multivariable analysis was carried out, risk factors associated with 90-day mortality were age, elevated Charlson comorbidity index, chronic statins intake and occurrence of an arterial thrombosis. CONCLUSION: In this cohort, age and number of comorbidities were the main predictors of mortality in invasively ventilated patients. The only modifiable factor associated with mortality in multivariate analysis was arterial thrombosis.

Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock.

BACKGROUND: Growing evidence suggests that the microvascular dysfunction is the key element of the pathogenesis of septic shock. This study's purpose was to explore whether the outcome of septic shock patients after early resuscitation using early goal-directed therapy is related to their muscle tissue oxygenation. METHODS: Tissue oxygen saturation (Sto2) was monitored in septic shock patients using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology, Hutchinson, MN). For the purpose of this retrospective study, the Sto2 values were collected at the first measurement done after the macrohemodynamic variables (mean arterial pressure, urine output, central venous saturation in oxygen) were optimized. RESULTS: After the hemodynamic variables were corrected, no difference was observed between the nonsurvivors and survivors, with the exception of pulse oximetry saturation (94% [92-97%] vs. 97% [94-99%], P = 0.04). The Sto2 values were significantly lower in the nonsurvivors than in the survivors (73% [68-82%] vs. 84% [81-90%], P = 0.02). No correlations were found between the Sto2 and Spo2 (P = 0.7). CONCLUSIONS: In septic shock patients, tissue oxygen saturation below 78% is associated with increased mortality at day 28. Further investigations are required to determine whether the correction of an impaired level of tissue oxygen saturation may improve the outcome of these patients.

Impact of terlipressin on renal graft function.

To assess the effect of a bolus of terlipressin in brain-dead donors with shock refractory to norepinephrine, a retrospective study was conducted in a 16-bed intensive care unit of a university hospital. Twenty brain-dead donors were treated with norepinephrine within the study period. Nine of these donors developed persisting hypotension (MAP < 65 mmHg) not responding to fluid loading and high dose of norepinephrine. They were then treated with a single bolus of terlipressin (1 mg). This resulted in a MAP rise from 58 +/- 10 to 93 +/- 20 mmHg (P = 0.009). One month after transplantation, no differences were observed in serum creatinine levels of the recipients who received a renal transplant extracted from donors responding or not to norepinephrine (138 +/- 43 vs. 137 +/- 43 microM; P = 0.95). The liver function was similar in both groups. Within the limitations of this study, a single bolus of terlipressin in norepinephrine-resistant vasodilatory shock donors does not affect the renal and liver graft quality in the recipients.

Craniocerebral penetrating injury caused by a spear gun through the mouth: case report.

The authors report a case of a craniocerebral penetrating injury caused by the shaft of a spear gun. The entry point of the spear was located in the mouth without an obvious exit point. The authors first note the presentation of the patient, whose airway was obstructed by the shaft, and then discuss the surgical procedure, which was focused on removing the shaft in an anterograde direction because of an articulated wishbone located at the tip of the shaft.

A novel intravascular rewarming method to treat severe hypothermia.

We report here a patient with severe hypothermia (27 degrees C), who was successfully rewarmed by using a novel intravascular rewarming method (in combination with an airways rewarming method) through endotracheal tube.

A randomized trial of catheter change and short course of antibiotics for asymptomatic bacteriuria in catheterized ICU patients.

OBJECTIVE: To determine the effect on the occurrence of urosepsis of a treatment with a short course of antibiotics and indwelling urethral catheter replacement in clinically asymptomatic intensive care unit (ICU) patients with a positive urine culture occurring at least 48 h after catheterization. METHODS: A prospective randomized clinical trial was conducted in the medico-surgical ICU of a tertiary care centre. Sixty patients hospitalized in the ICU with an indwelling urethral catheter for longer than 48 h developing an asymptomatic positive urine culture were randomized to receive either a 3-day course of antibiotics associated with the replacement of the indwelling urethral catheter 4 h after first antibiotic administration or no antibiotics, no catheter replacement (standard of care). RESULTS: Three patients in each group developed urosepsis (P=0.1). There were no significant differences in duration of mechanical ventilation between the study group and the standard of care group (9 [4-20] days vs 5 [2-15] days, P=0.2), in duration of urinary catheterization (22 [11-40] days vs 18 [14-33] days, P=0.8), or in length of ICU stay (28 [13-46] vs 19 [15-34], P=0.6). The recurrence of positive urine culture at days 7 and 15 was not affected by the randomization (P=0.1). The profile of bacterial resistance was similar in the two groups. CONCLUSIONS: Treating a positive urine culture in an asymptomatic patient with an indwelling urethral catheter does not reduce the occurrence of urosepsis in the medico-surgical ICU.

Impact of intensive care on renal function before graft harvest: results of a monocentric study.

BACKGROUND: The aim of life-support measures in brain-dead donors is to preserve the functional value of their organs. In renal transplantation, serum creatinine level is one of the criteria for graft harvest. The aim of this study was to assess the impact of intensive care on donor renal function through two criteria: preharvesting serum creatinine level above 120 micromol/L and the elevation of serum creatinine level above 20% between intensive care unit (ICU) admission and graft harvest. METHODS: Between 1 January 1999 and 31 December 2005, we performed an observational study on 143 brain-dead donors. ICU chronology, hemodynamic, hematosis, and treatment data were collected for each patient from ICU admission to kidney removal. RESULTS: Twenty-two percent of the 143 patients had a serum creatinine level above 120 micromol/L before graft harvest. The independent factors revealed by multivariate analysis were the administration of epinephrine (odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.33 to 14.32; p = 0.015), oliguria (OR: 3.73, 95% CI: 1.22 to 11.36; p = 0.021), acidosis (OR: 3.26, 95% CI: 1.07 to 9.95; p = 0.038), the occurrence of disseminated intravascular coagulation (OR: 3.97, 95% CI: 1.05 to 15.02; p = 0.042), female gender (OR: 0.13, 95% CI: 0.03 to 0.50; p = 0.003), and the administration of desmopressin (OR: 0.12, 95% CI: 0.03 to 0.44; p = 0.002). The incidence of elevated serum creatinine level above 20% between admission and graft harvest was 41%. The independent risk factors were the duration of brain death greater than 24 hours (OR: 2.64, 95% CI: 1.25 to 5.59; p = 0.011) and the volume of mannitol (OR: 2.08, 95% CI: 1.03 to 4.21; p = 0.041). CONCLUSION: This study shows that the resuscitation of brain-dead donors impacts on their renal function. The uses of epinephrine and mannitol are associated with impairment of kidney function. It seems that graft harvest should be performed less than 24 hours after brain death diagnosis.