Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial.

BACKGROUND: Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity. METHODS: Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m-2) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO2/FiO2 < 300 mm Hg). The primary outcome was the occurrence of severe hypoxemia (pulse oximetry < 80%) during the intubation procedure. RESULTS: Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m-2. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%; P = 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI - 13 to 25%; P = 0.54). The lowest pulse oximetry values during intubation procedure were 87% [interquartile range, 77-93] with noninvasive ventilation and 86% [78-92] with high-flow nasal oxygen (P = 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission. CONCLUSIONS: Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen. Trial registration Clinical trial number: NCT02668458 ( http://www.clinicaltrials.gov ).

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.

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

BACKGROUND: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. METHODS: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). RESULTS: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group. CONCLUSIONS: In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).

Randomized controlled trial of multidisciplinary team stress and performance in immersive simulation for management of infant in shock: study protocol.

BACKGROUND: Human error and system failures continue to play a substantial role in adverse outcomes in healthcare. Simulation improves management of patients in critical condition, especially if it is undertaken by a multidisciplinary team. It covers technical skills (technical and therapeutic procedures) and non-technical skills, known as Crisis Resource Management. The relationship between stress and performance is theoretically described by the Yerkes-Dodson law as an inverted U-shaped curve. Performance is very low for a low level of stress and increases with an increased level of stress, up to a point, after which performance decreases and becomes severely impaired. The objectives of this randomized trial are to study the effect of stress on performance and the effect of repeated simulation sessions on performance and stress. METHODS: This study is a single-center, investigator-initiated randomized controlled trial including 48 participants distributed in 12 multidisciplinary teams. Each team is made up of 4 persons: an emergency physician, a resident, a nurse, and an ambulance driver who usually constitute a French Emergency Medical Service team. Six multidisciplinary teams are planning to undergo 9 simulation sessions over 1 year (experimental group), and 6 multidisciplinary teams are planning to undergo 3 simulation sessions over 1 year (control group). Evidence of the existence of stress will be assessed according to 3 criteria: biological, electrophysiological, and psychological stress. The impact of stress on overall team performance, technical procedure and teamwork will be evaluated. Participant self-assessment of the perceived impact of simulations on clinical practice will be collected. Detection of post-traumatic stress disorder will be performed by self-assessment questionnaire on the 7(th) day and after 1 month. DISCUSSION: We will concomitantly evaluate technical and non-technical performance, and the impact of stress on both. This is the first randomized trial studying repetition of simulation sessions and its impact on both clinical performance and stress, which is explored by objective and subjective assessments. We expect that stress decreases team performance and that repeated simulation will increase it. We expect no variation of stress parameters regardless of the level of performance. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02424890.

Impact of simulation-based training in surgical chest tube insertion on a model of traumatic pneumothorax.

BACKGROUND: Chest tube insertion is required for most cases of traumatic pneumothorax. However, this procedure entails risks of potentially life-threatening complications. A "surgical" approach is widely recommended to minimize these risks. Simulation-based education has previously been used in surgical chest tube insertion, but not been subjected to rigorous evaluation. METHODS: The primary objective was to evaluate the success rate of surgical chest tube insertion in a task trainer (previously published). Secondary objectives were to assess performance with a performance assessment scale (previously designed), to measure the time of insertion, and to seek out a correlation between the learner's status, experience, and performance and success rate. Participants were surveyed for realism of the model and satisfaction; 65 participants (18 residents, 47 senior physicians) were randomized into SIM+ or SIM- groups. Both groups received didactic lessons. The SIM+ group was assigned deliberate practice on the model under supervision. Both groups were assessed on the model 1 month later. RESULTS: There was no difference between the SIM+ (n = 34) and SIM- (n = 31) groups regarding status (p = 0.44) or previous surgical insertion (p = 0.12). Success rate was 97 % (SIM+) and 58 % (SIM-), p = 0.0002. Performance score was 16.29 ± 1.82 (SIM+) and 11.39 ± 3.67 (SIM-), p = 3.13 × 10-8. SIM+ presented shorter dissection time than SIM- (p = 0.047), but procedure time was similar (p = 0.71). Status or experience was not correlated with success rate, performance score, procedure time, or dissection time. SIM+ gained more self-confidence, judged the model more realistic, and were more satisfied than SIM-. CONCLUSIONS: Simulation-based education significantly improved the success rate and performance of surgical chest tube insertion on a traumatic pneumothorax model.

Sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study.

BACKGROUND: The aim of this study was to evaluate the clinical efficacy of humidified oxygen via high-flow nasal cannula (HFNC) alternating with noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF). METHODS: We performed a prospective observational study in a 12-bed ICU of a university hospital. All subjects with a PaO2 /FIO2 of ≤300 mm Hg with standard mask oxygen and a breathing frequency of > 30 breaths/min or signs of respiratory distress were included and treated with HFNC first and then NIV. Ventilatory parameters, blood gases, and tolerance were recorded during 2 consecutive sessions of NIV and HFNC. Outcome was assessed after continuation of this noninvasive strategy. RESULTS: Twenty-eight subjects with AHRF were studied, including 23 (82%) with ARDS. Compared with standard oxygen therapy, PaO2 significantly increased from 83 (68-97) mm Hg to 108 (83-140) mm Hg using HFNC and to 125 (97-200) mm Hg using NIV (P<.01), whereas breathing frequency significantly decreased. HFNC was significantly better tolerated than NIV, with a lower score on the visual analog scale. The non-intubated subjects received HFNC for 75 (27-127) h and NIV for 23 (8-31) h. Intubation was required in 10 of 28 subjects (36%), including 8 of 23 subjects with ARDS (35%). After HFNC initiation, a breathing frequency of ≥30 breaths/min was an early factor associated with intubation. CONCLUSIONS: HFNC was better tolerated than NIV and allowed for significant improvement in oxygenation and tachypnea compared with standard oxygen therapy in subjects with AHRF, a large majority of whom had ARDS. Thus, HFNC may be used between NIV sessions to avoid marked impairment of oxygenation.

Recombinant human activated protein C for adults with septic shock: a randomized controlled trial.

RATIONALE: A decade after drotrecogin alfa (activated) (DAA) was released on the market worldwide, its benefit-to-risk ratio remains a matter of debate. OBJECTIVES: The current investigator-led trial was designed to evaluate the efficacy and safety of DAA, in combination with low-dose steroids, in adults with persistent septic shock. METHODS: This was a multicenter (24 intensive care units), placebo-controlled, double-blind, 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were randomly assigned to DAA alone (24 µg/kg/h for 96 h), hydrocortisone and fludrocortisone alone, their respective combinations, or their respective placebos. Primary outcome was mortality rate on Day 90. MEASUREMENTS AND MAIN RESULTS: On October 25, 2011, the trial was suspended after the withdrawal from the market of DAA. The Scientific Committee decided to continue the trial according to a two parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension. At the time trial was suspended, 411 patients had been recruited, 208 had received DAA, and 203 had received its placebo. There was no significant interaction between DAA and low-dose steroids (P = 0.47). On Day 90, there were 99 deaths (47.6%) among the 208 patients receiving DAA and 94 deaths (46.3%) among the 203 patients receiving placebo (P = 0.79). There was no evidence of a difference between DAA and its placebo for any secondary outcomes or serious adverse events. CONCLUSIONS: In adults with established and severe septic shock, DAA showed no evidence of benefit or harm. Clinical trial registered with www.clinicaltrials.gov (NCT00625209).

Factors associated with the mediastinal spread of cervical necrotizing fasciitis.

BACKGROUND: We conducted a study to determine factors associated with the occurrence of mediastinitis in patients hospitalized for cervical necrotizing fasciitis (CNF). METHODS: We reviewed the medical records of 130 consecutive patients in an intensive care unit (ICU) who were hospitalized with a diagnosis of CNF. Two radiologists reviewed cervical and thoracic computed tomography (CT) scans to determine the source and extension of the infection in each patient. RESULTS: Among the cohort of 130 patients with CNF, 37 (28%) had mediastinitis at the time of their admission (which in 13 cases was superior, or above the aortic arch, and in 24 cases inferior). Cervical necrotizing fasciitis complicated by mediastinitis resulted in a longer stay in the ICU than did CNF without mediastinitis, of a mean of 29 days (range, 18 to 39 days) versus 14 days (range, 9 to 19) days, respectively (p<0.0001). Multivariate analysis revealed that the presence of mediastinitis was associated with oral intake of glucocorticoids before admission (odds ratio [OR], 2.17; range, 0.99 to 4.76), a pharyngeal focus of CNF (OR, 2.17; range, 1.04 to 4.53), or gas seen on an initial CT scan (OR, 4.49; range, 2.15 to 9.38). Both a pharyngeal focus of fasciitis and the presence of gas were strong independent predictors of inferior mediastinitis (OR, 15.1; range, 4.9 to 46.4; p<0.0001). CONCLUSIONS: The present study is the first to describe three independent factors associated with extension of cervical fasciitis to the thoracic cavity, including glucocorticoid intake before admission, and confirms previous reports of a high incidence of mediastinitis in patients with CNF.

Pleth variability index predicts fluid responsiveness in critically ill patients.

OBJECTIVE: To investigate whether the pleth variability index, a noninvasive and continuous tool, can predict fluid responsiveness in mechanically ventilated patients with circulatory insufficiency. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Forty mechanically ventilated patients with circulatory insufficiency in whom volume expansion was planned by attending physician. Exclusion criteria included spontaneous respiratory activity, cardiac arrhythmia, known intracardiac shunt, severe hypoxemia (Pao2/Fio2 <100 mm Hg), contraindication for passive leg raising, left ventricular ejection fraction of <50%, and hemodynamic instability during the procedure. INTERVENTIONS: Fluid challenge with 500 mL of 130/0.4 hydroxyethyl-starch if respiratory variations in arterial pulse pressure were ≥ 13% or with passive leg raising if variations in arterial pulse pressure were <13%. MEASUREMENTS AND MAIN RESULTS: Pleth variability index, variations in arterial pulse pressure, and cardiac output estimated by echocardiography were recorded before and after fluid challenge. Fluid responsiveness was defined as an increase in cardiac output of ≥ 15%. Twenty-one patients were responders and 19 were nonresponders. Mean ± sd pleth variability index (28% ± 13% vs. 11% ± 4%) and arterial pulse pressure variation (22% ± 11% vs. 5% ± 2%) values at baseline were significantly higher in responders than in nonresponders. The pleth variability index threshold value of 17% allowed discrimination between responders and nonresponders with a sensitivity of 95% (95% confidence interval, 74% to 100%) and a specificity of 91% (95% confidence interval, 70% to 99%). The pleth variability index at baseline correlated (r = .72, p < .0001) with the percentage change in cardiac output induced by fluid challenge, suggesting that a higher pleth variability index at baseline will correlate with a higher percentage change in cardiac output after volume expansion. CONCLUSIONS: The pleth variability index can predict fluid responsiveness noninvasively in intensive care unit patients under mechanical ventilation.

Pharmacokinetics of ertapenem following intravenous and subcutaneous infusions in patients.

Steady-state pharmacokinetics of ertapenem were compared in patients after 1-g intravenous and subcutaneous (s.c.) infusions. Bioavailability was 99%+/-18% after s.c. administration, but peaks were reduced by about (43+/-29 versus 115+/-28 microg/ml) and times to peak were delayed. Simulations based on unbound concentrations show that time over the MIC should always be longer than 30% to 40% of the dosing interval, suggesting that s.c. infusion could be an alternative in patients with reduced vascular access.

Indwelling time and risk of colonization of peripheral arterial catheters in critically ill patients.

OBJECTIVE: Despite the lack of evidence to support routine scheduled replacement of peripheral arterial catheters this practice continues to be widely used in many intensive care units (ICU). This study evaluated whether additional risks of catheter colonization are incurred with a conservative attitude in severely ill patients. DESIGN AND SETTING: Observational study over a 18-month period in a 15-bed surgical ICU of a 1,000-bed French university-affiliated hospital. CATHETERS: A total of 295 peripheral arterial catheters were inserted in 295 patients. MEASUREMENTS AND MAIN RESULTS: Hazard rates of catheters colonization (defined as quantitative culture of a catheter tip showing at least one microorganism at a concentration of 1,000 or more colony-forming units per milliliter) according to indwelling time were determined over 5-day periods by survival analysis. The mean indwelling time was 8 +/- 6 days (median 6 days). Overall, 47 (16%) colonization episodes were diagnosed, leading to catheter colonization incidence density of 19.9 per 1,000 catheter-days. Risk factors for catheters colonization increase in proportion to the duration of catheter use. Hazard rates of catheter colonization were 1.0, 1.9, 3.5, 7.0, 6.0 and 5.7%, for the 111 arterial catheters left in place for 4 days or less, 5-9 days (87 catheters), 10-14 days (55 catheters), 15-19 days (27 catheters), 20-24 days (10 catheters) and more than 24 days (5 catheters). CONCLUSIONS: Systematic replacement of peripheral arterial catheters might be useful in preventing catheter-related colonization, especially after 2 weeks of use.

Chlorhexidine-based antiseptic solution vs alcohol-based povidone-iodine for central venous catheter care.

BACKGROUND: Although chlorhexidine-based solutions and alcohol-based povidone-iodine have been shown to be more efficient than aqueous povidone-iodine for skin disinfection at catheter insertion sites, their abilities to reduce catheter-related infection have never been compared. METHODS: Consecutively scheduled central venous catheters inserted into jugular or subclavian veins were randomly assigned to be disinfected with 5% povidone-iodine in 70% ethanol or with a combination of 0.25% chlorhexidine gluconate, 0.025% benzalkonium chloride, and 4% benzylic alcohol. Solutions were used for skin disinfection before catheter insertion (2 consecutive 30-second applications separated by a period sufficiently long to allow for dryness) and then as single applications during subsequent dressing changes (every 72 hours, or earlier if soiled or wet). RESULTS: Of 538 catheters randomized, 481 (89.4%) produced evaluable culture results. Compared with povidone-iodine, the chlorhexidine-based solution was associated with a 50% decrease in the incidence of catheter colonization (11.6% vs 22.2% [P = .002]; incidence density, 9.7 vs 18.3 per 1000 catheter-days) and with a trend toward lower rates of catheter-related bloodstream infection (1.7% vs 4.2% [P = .09]; incidence density, 1.4 vs 3.4 per 1000 catheter-days). Independent risk factors for catheter colonization were catheter insertion into the jugular vein (adjusted relative risk, 2.01; 95% confidence interval, 1.24-3.24) and use of povidone-iodine (adjusted relative risk, 1.87; 95% confidence interval, 1.18-2.96). CONCLUSION: Chlorhexidine-based solutions should be considered as a replacement for povidone-iodine (including alcohol-based) formulations in efforts to prevent catheter-related infection.