Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial.

PURPOSE: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia. METHODS: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28. RESULTS: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups. CONCLUSION: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.

Capillary lactate as a tool for the triage nurse among patients with SIRS at emergency department presentation: a preliminary report.

BACKGROUND: The triage nurse is involved in the early identification of the most severe patients at emergency department (ED) presentation. However, clinical criteria alone may be insufficient to identify them correctly. Measurement of capillary lactate concentration at ED presentation may help to discriminate these patients. The primary objective of this study was to identify the prognostic value of capillary lactate concentration measured by the triage nurse among patients presenting to the ED. METHODS: This was a prospective observational study, performed in the ED of a university hospital. At ED presentation, capillary lactate measurement was performed by the triage nurse among patients presenting with a clinical criteria of systemic inflammatory response syndrome (SIRS). Clinical variables usually used to determine severity were collected at presentation. Twenty-eight-day mortality and MEDS score were recorded. RESULTS: One hundred seventy-six patients with clinical SIRS presented to the ED. Median age was 72 years, and 28-day mortality was 16%. Capillary lactate at ED presentation was significantly higher among 28-day non-survivors than among survivors (5.7 mmol.L(-1) [3.2 to 7.4] vs 2.9 mmol.L(-1) [1.9 to 5.2], p = 0.003). A score based on mottling and capillary lactate concentration >3.6 mmol.L(-1) was significantly associated with 28-day mortality (area under curve, AUC = 0.75), independently of the MEDS score (AUC = 0.79) for the prediction of 28-day mortality (AUC global model 0.87). CONCLUSIONS: A high capillary lactate concentration measured by the triage nurse among patients presenting to the ED with clinical SIRS is associated with a high risk of death. A score calculated by the triage nurse, based on mottling and capillary lactate concentration, appears to be useful for identifying the most severe patients.

Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality.

OBJECTIVES: Small bowel dysfunction in critically ill patients is frequent, underdiagnosed, and associated with poor prognosis. Intestinal fatty acid-binding protein is a marker of enterocyte damage, and plasma citrulline concentration is a marker of functional enterocyte mass. Primary objective was to identify factors associated with intestinal fatty acid-binding protein in critically ill patients. Secondary objectives were to study factors associated with plasma citrulline concentration and its correlation with intestinal fatty acid-binding protein. DESIGN: Prospective observational study. SETTING: ICU in a University Hospital PATIENTS: Critically ill patients 18 years old or older with an expected length of ICU stay 48 hours or more, without pregnancy, chronic small bowel disease, or chronic renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma intestinal fatty acid-binding protein and citrulline concentrations, and variables relating to prognosis and treatment, were measured at admission to the ICU. One hundred and three patients were included. Intestinal fatty acid-binding protein elevation at admission to the ICU was associated with catecholamine support, higher lactate concentration, higher Sequential Organ Failure Assessment score, and higher international normalized ratio (all p≤0.001). Plasma citrulline concentration less than or equal to 10 µmol/L at admission to the ICU was associated with higher intra-abdominal pressure, higher plasma C reactive protein concentration, and more frequent antibiotic use (all p≤0.005). There was no correlation between plasma levels of intestinal fatty acid-binding protein and citrulline. At ICU admission, Sequential Organ Failure Assessment score≥12, plasma citrulline≤12.2 µmol/L, and plasma intestinal fatty acid-binding protein concentration≥355 pg/mL were all independently associated with 28-day mortality (odds ratio, 4.39 [1.48-13.03]; odds ratio, 5.17 [1.59-16.86]; and odds ratio, 4.46 [1.35-14.74], respectively). CONCLUSIONS: In critically ill patients, enterocyte damage is frequent, and it is significantly associated with shock and 28-day mortality. The link between intestinal fatty acid-binding protein and plasma citrulline concentrations in critically ill patients needs to be further evaluated.

Acute intestinal failure in critically ill patients: is plasma citrulline the right marker?

INTRODUCTION: Small bowel functions are more complex than colon functions, and short bowel conditions are associated with increased mortality. Gastrointestinal dysfunction in critically ill patients is common, probably underestimated, and associated with a poor prognosis. However, a validated definition of acute intestinal failure is lacking, in absence of a marker to measure it. Consequently, small bowel dysfunction is not clearly integrated into the overall approach used to treat ICU patients. MATERIALS AND METHODS: Review of the literature on gastrointestinal dysfunction in critically ill patients, and proposition of a definition of acute intestinal failure. CONCLUSION: On the one hand, small bowel ischemia is related to acute reduction of enterocyte mass and loss of gut barrier function by epithelial lifting of villi. On the other hand, systemic inflammatory response syndrome (SIRS) and sepsis could be linked to an acute dysfunction of enterocytes without enterocyte reduction. Citrulline is an amino acid mainly synthesized by small bowel enterocytes. Various contexts of chronic and acute reduction of enterocyte mass have been correlated with low plasma citrulline concentration. Critically ill patients with shock have an acute reduction of enterocyte mass and reduced gut citrulline synthesis, leading to a low plasma citrulline concentration. Acute intestinal failure could be defined as an acute reduction of enterocyte mass and/or acute dysfunction of enterocytes, associated or not with loss of gut barrier function. The influence of SIRS and acute renal failure on plasma citrulline concentration and the value of this concentration as an indicator of acute intestinal failure in critically ill patients must be further evaluated.

Hydrogen cyanide poisoning in a prison environment: a case report.

Cyanide poisoning is an important source of morbidity and mortality from smoke exposure in structural fires. This case involved administration of a cyanide antidote to a prisoner (male, 23 years) in France, discovered in cardiorespiratory arrest after about 30 minutes exposure to smoke from a burning mattress during an apparent suicide attempt. Smoke exposure, circulatory failure during initial resuscitation, and elevated blood cyanide and lactate led to the diagnosis of cyanide poisoning. Hydroxocobalamin (Cyanokit®), 5 g intravenous) was given immediately and on arrival at the hospital. Cardiopulmonary resuscitation restored cardiovascular function after 33 minutes. There were no neurological or other sequelae. Timely hydroxocobalamin administration contributed to full recovery from cardiorespiratory arrest secondary to cyanide poisoning from smoke inhalation. Hydroxocobalamin should be available to emergency medical teams attending fire scenes.

Acute ischemic pancreatitis following cardiac arrest: a case report.

CONTEXT: Ischemia is an established cause of acute pancreatitis; however, acute pancreatitis has never been reported after cardiac arrest. CASE REPORT: We report a case of acute pancreatitis following cardiac arrest with prolonged cardiopulmonary resuscitation in a 58-year-old man, the mechanism of which is likely to be ischemic. The patient developed severe ischemic encephalopathy, leading to death. Possible causes of acute pancreatitis in a context of cardiopulmonary resuscitation are discussed. CONCLUSION: In case of abdominal distension following cardiac arrest, diagnoses of mesenteric ischemia and acute ischemic pancreatitis should be considered. Such digestive complications occurring after cardiac arrest probably reflect the severity of the ischemia.

Recommendations for the intra-hospital transport of critically ill patients.

INTRODUCTION: This study was conducted to provide Intensive Care Units and Emergency Departments with a set of practical procedures (check-lists) for managing critically-ill adult patients in order to avoid complications during intra-hospital transport (IHT). METHODS: Digital research was carried out via the MEDLINE, EMBASE, CINAHL and HEALTHSTAR databases using the following key words: transferring, transport, intrahospital or intra-hospital, and critically ill patient. The reference bibliographies of each of the selected articles between 1998 and 2009 were also studied. RESULTS: This review focuses on the analysis and overcoming of IHT-related risks, the associated adverse events, and their nature and incidence. The suggested preventive measures are also reviewed. A check-list for quick execution of IHT is then put forward and justified. CONCLUSIONS: Despite improvements in IHT practices, significant risks are still involved. Basic training, good clinical sense and a risk-benefit analysis are currently the only deciding factors. A critically ill patient, prepared and accompanied by an inexperienced team, is a risky combination. The development of adapted equipment and the widespread use of check-lists and proper training programmes would increase the safety of IHT and reduce the risks in the long-term. Further investigation is required in order to evaluate the protective role of such preventive measures.

Cyanide poisoning and cardiac disorders: 161 cases.

BACKGROUND: Inhalation of hydrogen cyanide from smoke in structural fires is common, but cardiovascular function in these patients is poorly documented. OBJECTIVE: The objective was to study the cardiac complications of cyanide poisoning in patients who received early administration of a cyanide antidote, hydroxocobalamin (Cyanokit; Merck KGaA, Darmstadt, Germany [in the United States, marketed by Meridian Medical Technologies, Bristol, TN]). METHODS: The medical records of 161 fire survivors with suspected or confirmed cyanide poisoning were reviewed in an open, multicenter, retrospective review of cases from the Emergency Medical Assistance Unit (Service d'Aide Médical d'Urgence) in France. RESULTS: Cardiac arrest (61/161, 58 asystole, 3 ventricular fibrillation), cardiac rhythm disorders (57/161, 56 supraventricular tachycardia), repolarization disorders (12/161), and intracardiac conduction disorders (5/161) were observed. Of the total 161 patients studied, 26 displayed no cardiac disorder. All patients were given an initial dose of 5 g of hydroxocobalamin. Non-responders received a second dose of 5 g of hydroxocobalamin. Of the patients initially in cardiac arrest, 30 died at the scene, 24 died in hospital, and 5 survived without cardiovascular sequelae. Cardiac disorders improved with increasing doses of hydroxocobalamin, and higher doses of the antidote seem to be associated with a superior outcome in patients with initial cardiac arrest. CONCLUSIONS: Cardiac complications are common in cyanide poisoning in fire survivors.

Plasma citrulline kinetics and prognostic value in critically ill patients.

PURPOSE: Multiple organ failure is a leading cause of death in critically ill patients and could be secondary to early gut ischemia. Plasma citrulline is a biomarker of enterocyte mass, and critically ill patients may have enterocyte mass reduction. The objectives of this study were to assess plasma citrulline kinetics and its prognostic value in critically ill patients. METHODS: This prospective observational study included adults without small bowel disease and without chronic renal failure consecutively admitted to a single intensive care unit. Prognostic variables as well as plasma citrulline concentrations were studied at admission, 12, 24, 48 h, and the 7th day after admission. Univariate and multivariate analyses including plasma citrulline (0-10, 11-20, and >20 micromol l(-1)) and other variables were performed. RESULTS: Sixty-seven patients were included, and the 28-day mortality was 34%. During the 1st day mean plasma citrulline decreased from 18.8 to 13.5 micromol l(-1). Low plasma citrulline at 24 h was associated with low plasma glutamine and arginine (p = 0.01 and 0.04), and high plasma CRP concentration, nosocomial infection rate, and 28-day mortality (p = 0.008, 0.03, and 0.02, respectively). In multivariate analysis plasma citrulline < or = 10 micromol l(-1) at 24 h and SOFA score > or =8 at 24 h were associated with 28-day mortality(odds ratios 8.70 and 15.08). CONCLUSIONS: In critically ill patients, low plasma citrulline at 24 h is an independent factor of mortality and could be a marker of acute intestinal failure.