Non-invasive ventilation versus high-flow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial.

BACKGROUND: Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation. METHODS: The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France. Adult patients undergoing tracheal intubation for acute hypoxaemic respiratory failure (a partial pressure of arterial oxygen [PaO2] to fraction of inspired oxygen [FiO2] ratio of ≤300 mm Hg) were randomly assigned (1:1; block size, four participants) to non-invasive ventilation or high-flow oxygen during preoxygenation, with stratification by PaO2/FiO2 ratio (≤200 mm Hg vs >200 mm Hg). Key exclusion criteria were intubation for cardiac arrest, altered consciousness (defined as a Glasgow coma score of less than eight points), other contraindications to non-invasive ventilation (recent laryngeal, oesophageal, or gastric surgery, and substantial facial fractures), pulse oximetry not available, pregnant or breastfeeding women, and refusal to participate. The primary outcome was the occurrence of severe hypoxaemia (pulse oximetry <80%) during the procedure, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02668458. FINDINGS: Between April 15, 2016, and Jan 8, 2017, 2079 patients were intubated in the 28 participating units, and 322 were enrolled. We excluded five patients with no recorded data, two who withdrew consent or were under legal protection, one who was not intubated, and one who had a cardiac arrest. Of the 313 patients included in the intention-to-treat analysis, 142 were assigned to non-invasive ventilation and 171 to high-flow oxygen therapy. Severe hypoxaemia occurred in 33 (23%) of 142 patients after preoxygenation with non-invasive ventilation and 47 (27%) of 171 with high-flow oxygen (absolute difference -4·2%, 95% CI -13·7 to 5·5; p=0·39). In the 242 patients with moderate-to-severe hypoxaemia (PaO2/FiO2 ≤200 mm Hg), severe hypoxaemia occurred less frequently after preoxygenation with non-invasive ventilation than with high-flow oxygen (28 [24%] of 117 patients vs 44 [35%] of 125; adjusted odds ratio 0·56, 0·32 to 0·99, p=0·0459). Serious adverse events did not differ between treatment groups, with the most common immediate complications being systolic arterial hypotension (70 [49%] patients in the non-invasive ventilation group vs 86 [50%] patients in the high-flow oxygen group) and chest infiltrate on x-ray (28 [20%] vs 33 [19%]), and the most common late complications being death at day 28 (53 [37%] vs 58 [34%]) and ventilator-associated pneumonia during ICU stay (31 [22%] vs 35 [20%]). INTERPRETATION: In patients with acute hypoxaemic respiratory failure, preoxygenation with non-invasive ventilation or high-flow oxygen therapy did not change the risk of severe hypoxaemia. Future research should explore the effect of preoxygenation method in patients with moderate-to-severe hypoxaemia at baseline. FUNDING: French Ministry of Health.

Clinical consequences related to a defective elimination of clobazam caused by homozygous mutated CYP2C19 allele.

Introduction: Voluntary drug intoxication with benzodiazepines is common and in most cases without consequences. We report an interesting case of voluntary drug intoxication with clobazam (CLB) in a patient with a homozygous mutated CYP2C19 genotype. Case report: A 63-year-old Caucasian man was admitted to an intensive care unit for voluntary drug intoxication with CLB (1200 mg) complicated by prolonged hospitalization (46 days). The levels of CLB and N-desmethylclobazam (NCLB) in plasma were initially 8.3 and 14.8 mg/L. The persistence of a high concentration of NCLB (14.3 mg/L on day 30) suggested a lack of elimination. A homozygous mutated allele of CYP2C19*2 without enzyme activity was discovered. To overcome this phenotype, NCLB metabolism was induced by administering 100 mg of phenobarbital for 10 days, allowing patient improvement. Discussion: NCLB is the major active metabolite of CLB with a longer half-life and much higher steady-state plasma concentrations compared to the parent drug. The half-life elimination of CLB is 18 h that of NCLB is between 40 and 50 h. However, there is considerable inter-individual variation in the metabolism of CLB and of the report NCLB/CLB under the dependence of genotype of CYP2C19. These polymorphisms are not generally well-known by physicians and may lead to severe poisoning.

Correction: Enriched Air Nitrox Breathing Reduces Venous Gas Bubbles after Simulated SCUBA Diving: A Double-Blind Cross-Over Randomized Trial.

[This corrects the article DOI: 10.1371/journal.pone.0154761.].

Enriched Air Nitrox Breathing Reduces Venous Gas Bubbles after Simulated SCUBA Diving: A Double-Blind Cross-Over Randomized Trial.

OBJECTIVE: To test the hypothesis whether enriched air nitrox (EAN) breathing during simulated diving reduces decompression stress when compared to compressed air breathing as assessed by intravascular bubble formation after decompression. METHODS: Human volunteers underwent a first simulated dive breathing compressed air to include subjects prone to post-decompression venous gas bubbling. Twelve subjects prone to bubbling underwent a double-blind, randomized, cross-over trial including one simulated dive breathing compressed air, and one dive breathing EAN (36% O2) in a hyperbaric chamber, with identical diving profiles (28 msw for 55 minutes). Intravascular bubble formation was assessed after decompression using pulmonary artery pulsed Doppler. RESULTS: Twelve subjects showing high bubble production were included for the cross-over trial, and all completed the experimental protocol. In the randomized protocol, EAN significantly reduced the bubble score at all time points (cumulative bubble scores: 1 [0-3.5] vs. 8 [4.5-10]; P < 0.001). Three decompression incidents, all presenting as cutaneous itching, occurred in the air versus zero in the EAN group (P = 0.217). Weak correlations were observed between bubble scores and age or body mass index, respectively. CONCLUSION: EAN breathing markedly reduces venous gas bubble emboli after decompression in volunteers selected for susceptibility for intravascular bubble formation. When using similar diving profiles and avoiding oxygen toxicity limits, EAN increases safety of diving as compared to compressed air breathing. TRIAL REGISTRATION: ISRCTN 31681480.

Evaluation of Hyperbaric Oxygen Therapy in the Treatment of Radiation-induced Hemorrhagic Cystitis.

OBJECTIVE: To evaluate the efficacy of hyperbaric oxygen therapy (HBO) in the treatment of postradiation hematuria (PRH) and to identify the predictive factors for a successful outcome. MATERIALS AND METHODS: We conducted a retrospective study and included all patients with PRH treated with HBO in a university hospital center between January 2003 and December 2013. We studied the patients' clinical characteristics, radiotherapy indication, treatments preceding HBO, the grade of hematuria diagnosed based on the Common Terminology Criteria for Adverse Events classification v 4.03 and the efficacy of HBO. The success of HBO was defined as the total or partial resolution of hematuria. RESULTS: We included 71 patients with a median age of 72 (39-87) years. PRHs were severe (grade ≥3) in 50 (70.4%) of the cases. Radiotherapy was indicated in the treatment of prostate cancer in 61 (85.9%) patients. The median length of time between hematuria and HBO was 8 (1-154) months. Prior to HBO, 46 (64.8%) patients underwent electrocoagulation of the bladder. HBO sessions were compounded by 9 cases of barotraumatic otitis, 5 cases of transient visual disturbance, and 1 case of finger paresthesia. On average, 29 (3-50) sessions were carried out. Treatment was effective in 46 (64.8%) patients, 37 (52.1%) of whom were completely cured. A hematuria grade of less than 3 was a predictive factor in the successful treatment (P = .027). Median follow-up was 15 (1-132) months. CONCLUSION: HBO completely resolves PRH in 52.1% of cases. Prolonged patient follow-up is required to confirm the efficacy of this treatment.

Influence of ICU-bed availability on ICU admission decisions.

BACKGROUND: The potential influence of bed availability on triage to intensive care unit (ICU) admission is among the factors that may influence the ideal ratio of ICU beds to population: thus, high bed availability (HBA) may result in the admission of patients too well or too sick to benefit, whereas bed scarcity may result in refusal of patients likely to benefit from ICU admission. METHODS: Characteristics and outcomes of patient admitted in four ICUs with usual HBA, defined by admission refusal rate less than 11 % because of bed unavailability, were compared to patients admitted in six ICUs with usual low bed availability (LBA), i.e., an admission refusal rate higher than 10 % during a 90-day period. RESULTS: Over the 90 days, the mean number of days with no bed available was 30 ± 16 in HBA units versus 48 ± 21 in LBA units (p < 0.01). The proportion of admitted patients was significantly higher in the HBA (80.1 %; n = 659/823) than in the LBA units [61.6 %: n = 480/779; (p < 0.0001)]. The proportion of patients deemed too sick to benefit from admission was higher in LBA (9.0 %; n = 70) than in the HBA (6.3 %; n = 52) units (p < 0.05). The HBA group had a significantly greater proportion of patients younger than 40 years of age (22.5 %; n = 148 versus 14 %; n = 67 in LBA group; p < 0.001) and higher proportions of patients with either high or low simplified acute physiologic score II values. CONCLUSIONS: Bed availability affected triage decisions. Units with HBA trend to admit patients too sick or too well to benefit.

Successful medical treatment of glans ischemia after voluntary buprenorphine injection.

INTRODUCTION: The diverted use of synthetic opioid buprenorphine by drug addicts can be responsible for serious ischemic and infectious complications, particularly in the case of intravenous injection. AIM: We present a case of serious glans ischemia after buprenorphine injection directly into the deep dorsal vein of the penis. Analysis using new medical imaging techniques and treatments is detailed below. METHODS: A 26-year-old male drug addict presented with glans pain 4 days after self-injection of buprenorphine into the deep dorsal vein of the penis. The patient was apyretic and presented a urethral discharge. His glans was blue without discoloration on digital pressure. Additionally, his biologic and serologic tests were normal while bacteriology showed the presence of Enterobacter cloacae urethritis. RESULTS: After 48 hours of intravenous antibiotic treatment without improvement, a specific medical treatment using enoxaparin and ilomedin was initiated, with the assumption that there was an ischemic complication. Laser speckle contrast imaging allowed confirmation of the presence of distal penis ischemia and provided an accurate mapping of the ischemic zone. A 28-day treatment combining antibiotics, subcutaneous heparin at curative dose, antiplatelet drug, ilomedin, and hyperbaric oxygen therapy resulted in clinical improvement of the lesions with no functional complications. CONCLUSIONS: To date, no consensus exists on the proper diagnostic and treatment approach to severe glans ischemia due to buprenorphine injection into the deep dorsal vein of the penis. The results of laser speckle contrast imaging were of real interest during the process of diagnosis. In addition, the combination of ilomedin with hyperbaric oxygen therapy and anticoagulant and antiplatelet drugs appeared to be an effective therapy.

Refusal of intensive care unit admission due to a full unit: impact on mortality.

RATIONALE: Intensive care unit (ICU) beds are a scarce resource, and patients denied intensive care only because the unit is full may be at increased risk of death. OBJECTIVE: To compare mortality after first ICU referral in admitted patients and in patients denied admission because the unit was full. METHODS: Prospective observational multicenter cohort study of consecutive patients referred for ICU admission during two 45-day periods, conducted in 10 ICUs. MEASUREMENTS AND MAIN RESULTS: Of 1,762 patients, 430 were excluded from the study, 116 with previously denied admission to another ICU and 270 because they were deemed too sick or too well to benefit from ICU admission. Of the remaining 1,332 patients, 1,139 were admitted, and 193 were denied admission because the unit was full (65 were never admitted, 39 were admitted after bumping of another patient, and 89 were admitted on subsequent referral). Crude Day 28 and Day 60 mortality rates in the nonadmitted and admitted groups were 30.1 versus 24.3% (P = 0.07) and 33.3 versus 27.2% (P = 0.06), respectively. Day 28 mortality adjusted on age, previous disease, Glasgow scale score less than or equal to 8, shock, creatinine level greater than or equal to 250 µmol/L, and prothrombin time greater than or equal to 30 seconds was nonsignificantly higher in patients refused ICU admission only because of a full unit compared with patients admitted immediately. Patients admitted after subsequent referral had higher mortality rates on Day 28 (P = 0.05) and Day 60 (P = 0.04) compared with directly admitted patients. CONCLUSIONS: Delayed ICU admission due to a full unit at first referral is associated with increased mortality.

Percutaneous radiologic gastrostomy versus nasogastric tube in critically ill patients.

AIMS: To examine the feasibility of percutaneous radiologic gastrostomy in critically ill patients and to assess the rates of complications, esophagitis and gastroesophageal reflux when compared with nasogastric tube. METHOD: Sixty patients admitted to a medical intensive care unit and who were supposed to require gastric tubing for at least 14 days were randomized to have a nasogastric tube or a percutaneous radiologic gastrostomy. Patients with gastrostomy contraindication or gastric tubing for more than 2 days were excluded. RESULTS: No major complication requiring invasive treatment was observed. The nasogastric tube was more prone to failure as defined by the impossibility to place or to replace the allocated tube (P = 0.04) and to tube dysfunction (P<0.001), whereas gastrostomy was associated with increased incidence of minor local complications (P<0.001). Ten days after allocation, the rates of esophagitis (15%) and gastroesophageal reflux (24%) were not significantly different between the two groups. CONCLUSION: In selected critically ill patients, percutaneous radiologic gastrostomy carried a low risk of severe complication but we found no benefit in terms of esophagitis and gastroesphageal reflux between early performed gastrostomy and the nasogastric tube.