High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial.

BACKGROUND: Although non-invasive ventilation (NIV) is recommended for immunocompromised patients with acute respiratory failure in the intensive care unit (ICU), it might have deleterious effects in the most severe patients. High-flow nasal oxygen (HFNO) alone might be an alternative method to reduce mortality. We aimed to determine whether HFNO alone could reduce the rate of mortality at day 28 compared with HFNO alternated with NIV. METHODS: FLORALI-IM is a multicentre, open-label, randomised clinical trial conducted in 29 ICUs (28 in France and one in Italy). Adult immunocompromised patients with acute respiratory failure, defined as respiratory rate of 25 breaths per min or more and a partial pressure of arterial oxygen to inspired fraction of oxygen ratio of 300 mm Hg or lower, were randomly assigned (1:1) to HFNO alone (HFNO alone group) or NIV alternating with HFNO (NIV group). Key exclusion criteria were severe hypercapnia above 50 mm Hg, patients who could strongly benefit from NIV (ie, those with underlying chronic lung disease, with cardiogenic pulmonary oedema, or who were postoperative), severe shock, impaired consciousness defined as Glasgow coma score ≤12, urgent need for intubation, do not intubate order, and contraindication to NIV. Patients were assigned using computer-generated permuted blocks and were stratified according to centre and to the type of immunosuppression using a centralised web-based management system. In the HFNO alone group, patients were continuously treated by HFNO with a gas flow rate of 60 L/min or the highest tolerated. In the NIV group, patients were treated with NIV with a first session of at least 4 h, and then by sessions for a minimal duration of 12 h a day, with a dedicated ventilator, targeting a tidal volume below 8 mL/kg of predicted bodyweight, and with a positive end-expiratory level of at least 8 cm H2O. NIV sessions were interspaced with HFNO delivered as in the HFNO alone group. The primary outcome was mortality at day 28 and was assessed in the intention-to-treat population. Secondary outcomes were mortality in the ICU, in hospital, at day 90 and at day 180, intubation at day 28, length of stay in the ICU and in hospital, number of ventilator-free days at day 28, number of oxygenation technique-free days at day 28, and efficacy and tolerance of oxygenation techniques. The trial is registered with ClinicalTrials.gov, NCT02978300, and is complete. FINDINGS: Between Jan 21, 2017 to March 4, 2019, of 497 eligible patients, 300 were randomly assigned but one patient withdrew consent, leaving 299 patients included in the intention-to-treat analysis (154 assigned to the HFNO alone group and 145 assigned to NIV group). Mortality rate at day 28 was 36% (95% CI 29·2 to 44·2; 56 of 154 patients) in the HFNO alone group and 35% (27·9 to 43·2; 51 of 145 patients) in the NIV group (absolute difference 1·2% [95% CI -9·6 to 11·9]; p=0·83). None of the other prespecified secondary outcomes were different between groups except for greater decreased discomfort after initiation of HFNO than with NIV (-4 mm on visual analogic scale [IQR -18 to 4] vs 0 mm [-16 to 17]; p=0·040). INTERPRETATION: In critically ill immunocompromised patients with acute respiratory failure, the mortality rate did not differ between HFNO alone and NIV alternating with HFNO. However, study power was limited, so results should be interpreted with caution. FUNDING: French Ministry of Health.

Epidural analgesia in ICU chest trauma patients with fractured ribs: retrospective study of pain control and intubation requirements.

BACKGROUND: Nonintubated chest trauma patients with fractured ribs admitted to the intensive care unit (ICU) are at risk for complications and may require invasive ventilation at some point. Effective pain control is essential. We assessed whether epidural analgesia (EA) in patients with fractured ribs who were not intubated at ICU admission decreased the need for invasive mechanical ventilation (IMV). We also looked for risk factors for IMV. STUDY DESIGN AND METHODS: This retrospective, observational, multicenter study conducted in 40 ICUs in France included consecutive patients with three or more fractured ribs who were not intubated at admission between July 2013 and July 2015. RESULTS: Of the 974 study patients, 788 were included in the analysis of intubation predictors. EA was used in 130 (16.5%) patients, and 65 (8.2%) patients required IMV. Factors independently associated with IMV were chronic respiratory disease (P = 0.008), worse SAPS II (P < 0.0001), flail chest (P = 0.02), worse Injury Severity Score (P = 0.0003), higher respiratory rate at admission (P = 0.02), alcohol withdrawal syndrome (P < 0.001), and noninvasive ventilation (P = 0.04). EA was not associated with decreases in IMV requirements, median numerical rating scale pain score, or intravenous morphine requirements from day 1 to day 7. CONCLUSIONS: EA was not associated with a lower risk of IMV in chest trauma patients with at least 3 fractured ribs, moderate pain, and no intubation on admission. Further studies are needed to clarify the optimal pain control strategy in chest trauma patients admitted to the ICU, notably those with severe pain or high opioid requirements.

Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study.

BACKGROUND: The use of hydroxocobalamin has long been advocated for treating suspected cyanide poisoning after smoke inhalation. Intravenous hydroxocobalamin has however been shown to cause oxalate nephropathy in a single-center study. The impact of hydroxocobalamin on the risk of acute kidney injury (AKI) and survival after smoke inhalation in a multicenter setting remains unexplored. METHODS: We conducted a multicenter retrospective study in 21 intensive care units (ICUs) in France. We included patients admitted to an ICU for smoke inhalation between January 2011 and December 2017. We excluded patients discharged at home alive within 24 h of admission. We assessed the risk of AKI (primary endpoint), severe AKI, major adverse kidney (MAKE) events, and survival (secondary endpoints) after administration of hydroxocobalamin using logistic regression models. RESULTS: Among 854 patients screened, 739 patients were included. Three hundred six and 386 (55.2%) patients received hydroxocobalamin. Mortality in ICU was 32.9% (n = 243). Two hundred eighty-eight (39%) patients developed AKI, including 186 (25.2%) who developed severe AKI during the first week. Patients who received hydroxocobalamin were more severe and had higher mortality (38.1% vs 27.2%, p = 0.0022). The adjusted odds ratio (95% confidence interval) of AKI after intravenous hydroxocobalamin was 1.597 (1.055, 2.419) and 1.772 (1.137, 2.762) for severe AKI; intravenous hydroxocobalamin was not associated with survival or MAKE with an adjusted odds ratio (95% confidence interval) of 1.114 (0.691, 1.797) and 0.784 (0.456, 1.349) respectively. CONCLUSION: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03558646.

High-flow nasal oxygen therapy alone or with non-invasive ventilation in immunocompromised patients admitted to ICU for acute hypoxemic respiratory failure: the randomised multicentre controlled FLORALI-IM protocol.

INTRODUCTION: Non-invasive ventilation (NIV) is recommended as first-line therapy in respiratory failure of critically ill immunocompromised patients as it can decrease intubation and mortality rates as compared with standard oxygen. However, its recommendation is only conditional. Indeed, the use of NIV in this setting has been challenged recently based on results of trials finding similar outcomes with or without NIV or even deleterious effects of NIV. To date, NIV has been compared with standard oxygen but not to high-flow nasal oxygen therapy (HFOT) in immunocompromised patients. Several studies have found lower mortality rates using HFOT alone than when using HFOT with NIV sessions in patients with de novo respiratory failure, and even in immunocompromised patients. We are hypothesising that HFOT alone is more effective than HFOT with NIV sessions and reduces mortality of immunocompromised patients with acute hypoxemic respiratory failure. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing HFOT alone or with NIV in immunocompromised patients admitted to intensive care unit (ICU) for severe acute hypoxemic respiratory failure. Around 280 patients will be randomised with a 1:1 ratio in two groups. The primary outcome is the mortality rate at day 28 after inclusion. Secondary outcomes include the rate of intubation in each group, length of ICU and hospital stay and mortality up to day 180. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02978300.

Changes in limitations of life-sustaining treatments over time in a French intensive care unit: A prospective observational study.

BACKGROUND: Variability exists between ICUs in the limitations of therapy. Moreover practices may evolve over time. This single-center observational study aimed to compare withholding or withdrawing practices between 2012 and 2016. METHODS: For each period and patient concerned by limitations, withholding "do-not start", withholding "do-not-increase" and withdrawal measures were recorded. RESULTS: At a four-year interval, the rate of patients undergoing withholding or withdrawal rose from 10 to 23% and 4 to 7%, respectively. The proportion of patients dying in the ICU with previous limitations increased (53 to 89%), as did patients discharged alive despite withholding instructions (12 to 36%). The overall mortality (28%) was stable over time as the rate of failed resuscitation attempt declined (47 to 11%). In 2016 vs 2012, limitations started earlier following admission: 1 vs 7 days for withholding" do-not-start", 4 vs 8 for withholding "do-not-increase", 4 vs 7 for withdrawal. Notwithstanding the outcome and limitations applied, the median length of ICU stay of patients involved dropped from 13 days in 2012 to 8 days in 2016. CONCLUSION: A timely inclination to forego hopeless treatments resulted in a lower rate of failed resuscitations before death without change in global mortality.

Thank you letters from patients in an intensive care unit: From the expression of gratitude to an applied ethic of care.

INTRODUCTION: Patients' perception of an intensive care unit stay can lead to a better understanding of the expectations and needs of patients hospitalised in intensive care so that care for critically ill patients can be adapted and improved. Thank you letters are sources of original information which come directly and spontaneously from patients. OBJECTIVE: The objective of this study was to analyse the thank you letters from patients who required intensive care treatment and to identify messages that could be intended for the intensive care unit team. DESIGN: We conducted a qualitative study according to a thematic analysis. The body of research consisted of 17 letters from patients hospitalised in intensive care unit. SETTING: The study took place in the medical-surgical intensive care unit of a French general hospital. The intensive care unit is made up of 16 resuscitation beds and four continuous monitoring beds. FINDINGS: Two main themes emerged: (i) expression of gratitude through a description of the caregivers' behaviour (humanity and professionalism) and recognition for surviving (ii) the narrative of the intensive care unit experience. CONCLUSION: Thank you letters give a rich insight into how the patients perceived their stay in intensive care unit. Letters from patients give direct feedback on the quality of care provided, contribute to give meaning to work and raise the question of what the core values of care should be for all concerned in the healthcare providers-patients relationship.

High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.

BACKGROUND: Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS: We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS: A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

Fulminant course of unilateral emphysematous pyelonephritis revealing a renal actinomycosis caused by Actinomyces meyeri, an unknown cause of septic shock.

The objective of this case report is to describe the first case of renal actinomycosis caused by Actinomyces meyeri presenting as severe emphysematous pyelonephritis and complicated by septic shock and multi-organ failure. Emphysematous pyelonephritis is a potentially life-threatening infection mostly described in diabetic patients and predominantly caused by uropathogenic bacteria. Actinomycosis is an uncommon chronic infection due to anaerobic gram-positive bacteria that unusually involves the urinary tract. We report the first case of emphysematous pyelonephritis caused by A. meyeri in a 75-year-old non-diabetic woman. The patient presented with an altered status, fever, nausea, and vomiting lasting for 2 days. A computed tomography scan revealed unilateral emphysematous pyelonephritis. She was rapidly admitted to intensive care unit for a septic shock with multiple organ dysfunctions. A conservative management consisting in renal percutaneous drainage, supportive measures, and prolonged adapted antibiotic therapy resulted in complete recovery. This case report illustrates that renal actinomycosis should be considered in case of emphysematous pyelonephritis given the good prognosis of this infection with conservative medical treatment.

Eligibility of patients withheld or withdrawn from life-sustaining treatment to organ donation after circulatory arrest death: epidemiological feasibility study in a French Intensive Care Unit.

BACKGROUND: Transplantation brings sustainably improved quality of life to patients with end-stage organ failure. Persisting shortfall in available organs prompted French authorities and practitioners to focus on organ retrieval in patients withdrawn from life-sustaining treatment and awaiting cardiac arrest (Maastricht classification category III). The purpose of this study was to assess the theoretical eligibility of non-heart-beating donors dying in the intensive care unit (ICU) after a decision to withhold or withdraw life-sustaining treatment (WoWt). METHODS: We collected the clinical and biological characteristics of all consecutive patients admitted to our ICU and qualified for a WoWt procedure under the terms of the French Leonetti law governing end-of-life care during a 12-month period. The theoretical organ donor eligibility (for kidney, liver, or lung retrieval) of deceased patients was determined a posteriori 1) according to routine medical criteria for graft selection and 2) according to the WoWt measures implemented and their impact on organ viability. RESULTS: A total of 596 patients (mean age: 67 ± 16 yr; gender ratio M/F: 1.6; mean SAPS (Simplified Acute Physiology Score) II: 54 ± 24) was admitted to the ICU, of which 84 patients (mean age: 71 ± 14 yr, 14% of admissions, gender ratio M/F: 3.2) underwent WoWt measures. Eight patients left the unit alive. Forty-four patients presented a contraindication ruling out organ retrieval either preexisting admission (n = 20) or emerged during hospitalization (n = 24). Thirty-two patients would have been eligible as kidney (n = 23), liver (n = 22), or lung donors (n = 2). Cardiopulmonary support was withdrawn in only five of these patients, and three died within 120 minutes after withdrawal (the maximum delay compatible with organ viability for donor grafts). CONCLUSIONS: In this pilot study, a significant number of patients deceased under WoWt conditions theoretically would have been eligible for organ retrieval. However, the WoWt measures implemented in our unit seems incompatible with donor organ viability. A French multicenter survey of end-of-life practices in ICU may help to identify potential appropriate organ donors and to interpret nation-specific considerations of the related professional, legal, and ethical frameworks.

Star fruit poisoning is potentially life-threatening in patients with moderate chronic renal failure.

PURPOSE: Star fruit intoxications have been reported mainly in uremic patients, leading to various degrees of neurological symptoms and potentially fatal outcomes. Nephrotoxicity has been reported in few patients with normal renal function or moderate chronic renal impairment (CRI). The present report describes clinical course, management, and outcome of six patients with moderate CRI admitted to ICU for severe star fruit intoxication. METHODS: Over a 1-year period we observed six cases of star fruit intoxication. All but two patients were prospectively monitored. For each case we collected clinical characteristics, management, and outcome. RESULTS: On admission, all patients presented acute renal failure with underlying moderate CRI and required intubation for coma. The most common symptoms were hiccups, mental confusion, seizures, and coma. Status epilepticus was authenticated in three patients. Management consisted of several methods of renal replacement therapy (RRT) and supportive measures. Four patients survived without sequelae and two patients died. CONCLUSIONS: Severe star fruit intoxication can occur in patients with moderate CRI with a potentially fatal outcome. Prompt continuous RRT should be instituted.

The bilateral superficial cervical plexus block with 0.75% ropivacaine administered before or after surgery does not prevent postoperative pain after total thyroidectomy.

BACKGROUND AND OBJECTIVES: Patients undergoing thyroid surgery need postoperative pain management. Bilateral superficial cervical plexus block by administration of 0.25% bupivacaine with 1:200000 epinephrine at the end of surgery has been shown to improve postoperative analgesia. The objective of this study was to assess the analgesic efficacy in the first 36 postoperative hours after total thyroidectomy of bilateral superficial cervical plexus block with 0.75% ropivacaine administered before the incision or on completion of the surgical procedure. METHODS: We performed a prospective double-blinded, randomized controlled trial that compared 3 parallel groups: the CONT group did not receive any block, the PRE group received bilateral superficial cervical plexus block before surgery while under general anesthesia, and the POST group received bilateral superficial cervical plexus block after surgery while under general anesthesia. The study included 111 patients (37 in each group). Postoperative pain was assessed every 4 hours by use of a 0 to 10 numeric rating scale. All patients received paracetamol every 6 hours. Morphine was administered following a standardized protocol if the numeric rating scale was 4 or higher. The main outcome variables were the proportion of patients given morphine during the 36 hours period, pain intensity scores, and morphine consumption. RESULTS: No intergroup differences were observed in terms of percentage of patients who required morphine, morphine delivery, pain scores, and intraoperative opioid consumption. CONCLUSIONS: Bilateral superficial cervical plexus block with 0.75% ropivacaine administered before or after surgery does not improve postoperative analgesia after total thyroidectomy.