Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest: The CYRUS Randomized Clinical Trial.

IMPORTANCE: Experimental evidence suggests that cyclosporine prevents postcardiac arrest syndrome by attenuating the systemic ischemia reperfusion response. OBJECTIVE: To determine whether early administration of cyclosporine at the time of resuscitation in patients with out-of-hospital cardiac arrest (OHCA) would prevent multiple organ failure. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, single-blind, randomized clinical trial was conducted from June 22, 2010, to March 13, 2013 (Cyclosporine A in Out-of-Hospital Cardiac Arrest Resuscitation [CYRUS]). Sixteen intensive care units in 7 university-affiliated hospitals and 9 general hospitals in France participated. A total of 6758 patients who experienced nonshockable OHCA (ie, asystole or pulseless electrical activity) were assessed for eligibility. Analyses were performed according to the intention-to-treat analysis. INTERVENTIONS: Patients received an intravenous bolus injection of cyclosporine, 2.5 mg/kg, at the onset of advanced cardiovascular life support (cyclosporine group) or no additional intervention (control group). MAIN OUTCOMES AND MEASURES: The primary end point was the Sequential Organ Failure Assessment (SOFA) score, assessed 24 hours after hospital admission, which ranges from 0 to 24 (with higher scores indicating more severe organ failure). Secondary end points included survival at 24 hours, hospital discharge, and favorable neurologic outcome at discharge. RESULTS: Of the 6758 patients screened, 794 were included in intention-to-treat analysis (cyclosporine, 400; control, 394). The median (interquartile range [IQR]) ages were 63.0 (54.0-71.8) years for the cyclosporine group and 66.0 (57.0-74.0) years for the control group. The cohorts included 293 men (73.3%) in the treatment group and 288 men (73.1%) in the control group. At 24 hours after hospital admission, the SOFA score was not significantly different between the cyclosporine (median, 10.0; IQR, 7.0-13.0) and the control (median, 11.0; IQR, 7.0-15.0) groups. Survival was not significantly different between the 98 (24.5%) cyclosporine vs 101 (25.6%) control patients at hospital admission (adjusted odds ratio [aOR], 0.94; 95% CI, 0.66-1.34), at 24 hours for 67 (16.8%) vs 62 (15.7%) patients (aOR, 1.08; 95% CI, 0.71-1.63), and at hospital discharge for 10 (2.5%) vs 5 (1.3%) patients (aOR, 2.00; 95% CI, 0.61-6.52). Favorable neurologic outcome at discharge was comparable between the cyclosporine and control groups: 7 (1.8%) vs 5 (1.3%) patients (aOR, 1.39; 95% CI, 0.39-4.91). CONCLUSION AND RELEVANCE: In patients presenting with nonshockable cardiac rhythm after OHCA, cyclosporine does not prevent early multiple organ failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01595958; EudraCT Identifier: 2009-015725-37.

Covered Stent and Coils Embolization of a Pulmonary Artery Pseudoaneurysm After Gunshot Wound.

We report the first case of endovascular covered stent implantation for the treatment of a large pulmonary artery pseudoaneurysm (PAPA) following a right thoracic gunshot wound. After resuscitation and hemodynamic stabilization, a CT angiography was performed to analyze the neck size of the PAPA and its position relative to the branches of the parent artery. Covered stent implantation with additional coil embolization was successfully performed. At the 4-year follow-up, the stents remained patent and there was neither pseudoaneurysm recurrence nor treatment-related complication.

Prone positioning in severe acute respiratory distress syndrome.

BACKGROUND: Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilatory support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS. METHODS: In this multicenter, prospective, randomized, controlled trial, we randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (FiO2) of less than 150 mm Hg, with an FiO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. RESULTS: A total of 237 patients were assigned to the prone group, and 229 patients were assigned to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. CONCLUSIONS: In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT00527813.).

The feasibility of early physical activity in intensive care unit patients: a prospective observational one-center study.

BACKGROUND: Prolonged immobilization may harm intensive care unit (ICU) patients, and early mobilization has been proposed to counteract that process. We describe our experience in early rehabilitation of ICU patients, and its effects on physiologic outcomes. METHODS: We included all patients who stayed in our 14-bed medical ICU for > or = 7 days and received invasive mechanical ventilation for > or = 2 days. The rehabilitation program included chair-sitting, tilting-up (with arms supported or unsupported), and walking. We collected vital signs before and after each intervention. RESULTS: Over a 5-month period we studied 20 patients, after a median ICU stay of 5 days. A contraindication to the intervention was present on 230 days (43%). Sedation (15%), shock (11%), and renal support (9%) were the most frequent contraindications. We obtained complete data from 275 of 424 interventions, 33% of which were performed during mechanical ventilation. The chair-sitting intervention was the most frequent (56%), followed by the tilting-up-with-arms-unsupported intervention (25%), the walking intervention (11%), and the tilting-up arms-supported intervention (8%). The chair-sitting intervention was associated with a significant (P = .03) decline in both heart rate (mean -3.5 beats/min, 95% confidence interval [CI] -6.5 to -0.4 beats/min) and respiratory rate (-1.4 breaths/min, 95% CI -2.6 to 0.1 breaths/min), whereas blood oxygen saturation (measured via pulse oximetry [S(pO(2))]) and mean arterial blood pressure did not change significantly. Heart rate and respiratory rate similarly increased with tilting-up: 14.6 beats/min, 95% CI 10.8 to 18.4 beats/min, and 5.5 breaths/min, 95% CI 3.6 to 7.3 breaths/min with arms unsupported, and 12.4 beats/min, 95% CI 7.0 to 17.9 beats/min and 2.6 breaths/min, 95% CI -0.4 to 5.7 breaths/min with arms supported). Heart rate and respiratory rate also increased with the walking intervention: 6.9 beats/min, 95% CI 2.6 to 11.1 beats/min, and 5.9 breaths/min, 95% CI 3.8 to 8.0 breaths/min. The walking intervention significantly decreased S(pO(2)). An adverse event occurred in 13 (3%) of 424 interventions, but none had harmful consequences. CONCLUSIONS: Early rehabilitation is feasible and safe in patients in the ICU for longer than 1 week. The chair-sitting intervention was associated with nonsignificant oxygenation improvement. The tilting-up intervention was an effort as intense as walking.

Comparison of optimal positive end-expiratory pressure and recruitment maneuvers during lung-protective mechanical ventilation in patients with acute lung injury/acute respiratory distress syndrome.

BACKGROUND: In patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the use of alveolar-recruitment maneuvers to improve oxygenation is controversial. There is lack of standardization and lack of clinical studies to compare various recruitment maneuvers. Recruitment maneuvers are closely linked to the selection of positive end-expiratory pressure (PEEP), which is also a subject of debate. METHODS: With 12 intubated and mechanically ventilated patients with early ALI/ARDS we conducted a recruitment maneuver (sustained inflation at 40 cm H(2)O for 30 s), then set PEEP at 24 cm H(2)O, and then we reduced PEEP stepwise, by 4 cm H(2)O every 10 min. We kept the fraction of inspired oxygen (F(IO(2))) at 0.8. After each PEEP decrement step we measured P(aO(2)). We defined the "optimal" PEEP as the PEEP step above which P(aO(2)) decreased by > or = 20%. All the patients then underwent a period of ventilation on the same settings: tidal volume 6 mL/kg, PEEP at the level set by the physician before the experiment, plateau pressure < 30 cm H(2)O. Then each patient underwent 3 ventilation strategies, each applied for one hour: optimal PEEP alone; optimal PEEP plus one sustained inflation (40 cm H(2)O for 30 s); and optimal PEEP plus sigh breaths (ie, twice the baseline tidal volume, plateau pressure < 40 cm H(2)O) every 25 breaths. After the application of each PEEP strategy we measured arterial blood gas values and the static compliance of the respiratory system. RESULTS: The mean +/- SD optimal PEEP was 12 +/- 4 cm H(2)O. The measurements from the standardization periods were comparable between the 3 PEEP groups. In the optimal-PEEP-plus-sighs group the changes in P(aO(2)) (85 +/- 96%) and static compliance (14 +/- 20%) were significantly greater than in the 2 other groups. CONCLUSIONS: Sighs superimposed on lung-protective mechanical ventilation with optimal PEEP improved oxygenation and static compliance in patients with early ALI/ARDS.

Circumstances of death in hospitalized patients and nurses' perceptions: French multicenter Mort-a-l'Hôpital survey.

BACKGROUND: In developed countries at present, death mostly occurs in hospitals, but the circumstances and factors associated with the quality of organization and care surrounding death are not well described. METHODS: We designed a large multicenter cross-sectional study to analyze the setting and clinical course of each patient on the day of death. We included 2750 clinical departments of 294 hospitals. Of these, 1033 departments (37.6%) of 200 hospitals (68.0%) contributed to the Mort-a-l'Hôpital survey. Data were collected prospectively by the bedside nurse of each patient within 10 days of the occurrence of death. Main outcome measures included circumstances of death in hospitalized patients; secondary outcomes, nurses' perceptions of quality of end-of-life care. RESULTS: Of the 1033 participating departments, 420 recorded no deaths during the study period and 613 declared at least 1 death. In the 3793 patients who died and were included for assessment, only 925 (24.4%) had loved ones present at the time of death; 70.1% had respiratory distress during the period before death; and only 12.0% were in pain. Written protocols for end-of-life care were available in 12.2% of participating departments. Only 35.1% of nurses judged the quality of dying and death acceptable for themselves. Principal factors significantly associated with this perception were availability of a written protocol for end-of-life care, anticipation of death, informing the family, surrogate designation, adequate control of pain, presence of family or friends at the time of death, and staff meeting with the family after the death. CONCLUSIONS: This large prospective study identifies nonoptimal circumstances of death for hospitalized patients and a number of suggestions for improvement. A combination of factors reflected in the nurses' satisfaction may improve the quality of end-of-life care.

Viscoelastic properties of lungs and thoracic wall of anesthetized mechanically ventilated piglets.

OBJECTIVE: To investigate the viscoelastic properties of lungs and thoracic wall in piglets. STUDY DESIGN: Prospective experimental study. ANIMALS: Six piglets weighting 30 kg. METHODS: Animals were tracheotomized, anesthetized and mechanically ventilated under controlled conditions. After control measurements of the mechanical properties of the lung of the pigs had been taken, acute lung injury (ALI) was induced by saline lavage. Lung and thoracic wall tissue resistance (DeltaR), which reflects viscoelastic properties and/or time constant inequalities, were determined by using a rapid airway occlusion technique during constant flow inflation (V), at constant tidal volume. was varied from 0.1-0.2 to 1.2 L second(-1) on a single breath. Multiple data sets of DeltaR of lung (DeltaR(L)) and thoracic wall (DeltaR(w)) to inspiratory time (T(I) = V(T)/V) were fitted to a model whose prediction equation was DeltaR = R(2)[1 -exp(-T(I)/tau(2))], where R(2) and tau(2) are the 'viscoelastic' resistance and time constant, respectively. Subscripts (L) and (W) are used to represent lung and thoracic wall, respectively (R(2L), R(2W), tau(2L), tau(2W)). Two more sets of physiological measurements were then taken--the first under zero end-expiratory pressure (ZEEP) and the second under a positive end-expiratory pressure (PEEP) of 10 cmH(2)O. RESULTS: Data of DeltaR adequately fitted to the prediction equation in all instances. In control, R(2,L) was 15.3 (10.7-22.6) cmH(2)O L(-1) second(-1) (median, interquartile range), tau(2,L) 3.3 (1.9-5.5) seconds, R(2,w) 6.5 (2.2-10.3) cmH(2)O L(-1) second(-1) and tau(2,w) 2.9 (1.1-4.3) seconds. In ALI, R(2,L) significantly increased to 129.6 (105.9-171.3) cmH(2)O L(-1) second(-1) on ZEEP but not significantly decreased to 48.9 (17.8-109.6) cmH(2)O L(-1) second(-1) with PEEP. The corresponding values of tau(2,L) were 7.1 (5.1-11.6) and 4.4 (3.1-5.5) seconds. The values pertaining to thoracic wall did not change significantly among conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Viscoelastic properties of the lung and thoracic wall in piglets can be described by a viscoelastic model. Values of parameters of this model were markedly increased in ALI and decreased with PEEP.

Assessment of airway closure from deflation lung volume-pressure curve: sigmoidal equation revisited.

OBJECTIVE: To assess a sigmoidal equation for describing airway closure. DESIGN: Experimental study. SETTING: University laboratory. PARTICIPANTS: Eight piglets mechanically ventilated on zero end-expiratory pressure (ZEEP). INTERVENTIONS: Control and lung saline lavage. MEASUREMENTS AND RESULTS: Lungs were inflated up to transpulmonary pressure of 30 cmH(2)O at constant flow (0.12l s(-1)) then deflated at the same flow rate up to the point at which oesophageal pressure was constant, which was assumed to represent complete airway closure. The deflation volume-transpulmonary pressure curve was fitted to: (1) a sigmoidal equation focusing on inflexion point and pressure at maximal compliance increase and (2) an exponential equation above an inflexion point determined by eyeballing. Data deviate from the exponential equation at the point of airway closure onset. The zero-volume intercept was determined. Complete airway closure was reached at -8.3+/-3.5cmH(2)O in control conditions and at -1.3+/-3.7 cmH(2)O after lavage (p < 0.05). Between control and lavage, onset of airway closure was 3.0+/-1.9 vs. 6.0+/-2.8 cmH(2)O (p <0.05), inflexion point 3.2+/-1.8 vs. 7.7+/-2.6 cmH(2)O (p <0.001), pressure at maximal compliance increase -1.9+/-0.7 vs. -0.03+/-2.1cmH(2)O (p <0.05) and zero-volume intercept -1.5+/-1.4 vs. 0.3+/-2.3cmH(2)O (p <0.05). CONCLUSIONS: During mechanical ventilation airways stay open and close around ZEEP in control but are closed above ZEEP after lavage. Inflexion point might reflect onset of airways closure in control. Pressure at maximal compliance increase was not a marker of complete airways closure. In control and lavage, pressure at maximal compliance increase and zero-volume intercept were reasonably equivalent.

Effects of inhaled fenoterol and positive end-expiratory pressure on the respiratory mechanics of patients with chronic obstructive pulmonary disease.

BACKGROUND: During acute ventilatory failure in patients with chronic obstructive pulmonary disease (COPD), applying external positive end-expiratory pressure (PEEPe) will reopen small airways and, thus, may enhance peripheral deposition as well as the physiological effects of inhaled beta-2 agonists. OBJECTIVE: To investigate the efficacy of inhaled fenoterol applied by zero end-expiratory pressure (ZEEPe) or PEEPe. METHODS: Ten patients with COPD who were intubated and mechanically ventilated received fenoterol (10 mg/4 mL) via the ventilator using a jet nebulizer for 30 min on ZEEPe and PEEPe set at 80% of the total PEEP in a random order. The total resistance of the respiratory system (rapid airway occlusion technique), change in end-expiratory lung volume and expiratory flow limitation were assessed before and 5 min, 15 min, 30 min, 60 min and 240 min after fenoterol inhalation. RESULTS: Before inhalation and 60 min after inhalation, the total PEEP, the change in end-expiratory lung volume and the total resistance of the respiratory system were 8+/-3 cmH2O and 6+/-3 cmH2O, 0.61+/-0.34 L and 0.43+/-0.32 L, and 26+/-7 cmH2O/L/s and 23+/-6 cmH2O/L/s, respectively, with ZEEPe, and 9+/-3 cmH2O and 8+/-3 cmH2O (P<0.05 versus ZEEPe), 0.62+/-0.34 L and 0.62+/-0.37 L (P<0.05 versus ZEEPe), and 26+/-9 H2O/L/s and 25+/-9 H2O/L/s, respectively, with PEEPe. Three patients became not flow-limited under the combination of PEEPe and fenoterol. CONCLUSIONS: In patients with COPD, fenoterol combined with PEEPe has opposing effects on respiratory mechanics. First, it does not significantly reduce lung hyperinflation or inspiratory resistances. Second, it allows expiratory flow limitation reversal in some patients. These findings result from the net effect on end-expiratory lung volume of each intervention. This implies that if fenoterol is used in combination with PEEPe, the level of PEEPe should be reassessed during the time course of the drug to prevent any further lung hyperinflation.

Sigmoidal equation for lung and chest wall volume-pressure curves in acute respiratory failure.

To assess incidence and magnitude of the "lower inflection point" of the chest wall, the sigmoidal equation was used in 36 consecutive patients intubated and mechanically ventilated with acute lung injury (ALI). They were 21 primary and 5 secondary ALI, 6 unilateral pneumonia, and 4 cardiogenic pulmonary edema. The lower inflection point was estimated as the point of maximal compliance increase. The low constant flow inflation method and esophageal pressure were used to partition the volume-pressure curves into their chest wall and lung components on zero end-expiratory pressure. The sigmoidal equation had an excellent fit with coefficients of determination >0.90 in all instances. The point of maximal compliance increase of the chest wall ranged from 0 to 8.3 cmH2O (median 1 cmH2O) with no difference between ALI groups. The chest wall significantly contributed to the lower inflection point of the respiratory system in eight patients only. The occurrence of a significant contribution of the chest wall to the lower inflection point of the respiratory system is lower than anticipated. The sigmoidal equation is able to determine precisely the point of the maximal compliance increase of lung and chest wall.

Discrepancies between perceptions by physicians and nursing staff of intensive care unit end-of-life decisions.

Several studies have pointed out ethical shortcomings in the decision-making process for withholding or withdrawing life-supporting treatments. We conducted a study to evaluate the perceptions of all caregivers involved in this process in the intensive care unit. A closed-ended questionnaire was completed by 3,156 nursing staff members and 521 physicians from 133 French intensive care units (participation rate, 42%). Decision-making processes were perceived as satisfactory by 73% of physicians and by only 33% of the nursing staff. More than 90% of caregivers believed that decision-making should be collaborative, but 50% of physicians and only 27% of nursing staff members believed that the nursing staff was actually involved (p < 0.001). Fear of litigation was a reason given by physicians for modifying information given to competent patients, families, and nursing staff. Perceptions by nursing staff may be a reliable indicator of the quality of medical decision-making processes and may serve as a simple and effective tool for evaluating everyday practice. Recommendations and legislation may help to build consensus and avoid conflicts among caregivers at each step of the decision-making process.

Time course of expiratory flow limitation in COPD patients during acute respiratory failure requiring mechanical ventilation.

STUDY OBJECTIVES: (1) To determine the incidence of expiratory flow limitation (FL) at ICU admission, at the time of extubation, and at ICU discharge in intubated patients with COPD receiving mechanical ventilation for acute respiratory failure (ARF); and (2) to assess the feasibility of inspiratory capacity (IC) as an indication of pulmonary dynamic hyperinflation in this setting. DESIGN: Prospective, observational pilot study with physiologic measurements performed at ICU admission and during the weaning process driven by the clinician. A 60-min T-tube trial was initiated once criteria for weaning were present. The decision to extubate or reventilate patients was made by the clinician at the end of this session. Assessment of failure or success of T-tube trials was performed independently. SETTING: A 25-bed ICU of a tertiary teaching university hospital. PATIENTS: Over a 13-month period, 25 intubated patients with COPD receiving mechanical ventilation for ARF were included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: At ICU admission, FL assessed by the negative expiratory pressure test was measured under passive ventilatory conditions at the baseline ventilatory settings, on zero end-expiratory pressure, and in a semirecumbent position. During weaning, FL, respiratory pattern, and IC were measured during T-tube trials, before extubation, 1 h after extubation, and at ICU discharge. At ICU admission, 24 of 25 patients presented FL with, on average, 73 +/- 22% of the tidal volume. Ten patients were unavailable for follow-up due to death (n = 6) unplanned extubation (n = 3), or refusal (n = 1), so that only 15 patients completed the whole protocol (all 15 patients were extubated). For these 15 patients, the incidence of FL was 93% at ICU admission, 47% before extubation, and 40% at ICU discharge. IC was significantly greater at ICU discharge than before extubation (36 +/- 11% predicted vs 44 +/- 12% predicted, p < 0.01) and in successful T-tube trials compared with unsuccessful T-tube trials (38 +/- 13% predicted vs 24 +/- 8% predicted, p < 0.01). CONCLUSIONS: The incidence of expiratory FL is high in patients with COPD receiving mechanical ventilation, and is reduced during aggressive therapy when the patient is placed on mechanical ventilatory support and the time that weaning begins during the ICU stay. IC was lower in patients in whom weaning was unsuccessful. Further large-scale studies are required to confirm these preliminary results.

Inhaled corticosteroids in chronic obstructive pulmonary disease and disseminated aspergillosis.

Inhaled corticosteroids are widely used in patients with chronic obstructive pulmonary disease (COPD), although their efficacy is still being debated. Due to local and systemic effects, such therapy can have an immunosuppressive action and opportunistic infections can occur. In the present case, a 74-year-old man treated with inhaled corticosteroids for 5 years developed disseminated aspergillosis. No other immunosuppressive factor was found. To our knowledge, only a few cases of lung aspergillosis in such patients have been described in the literature. However, the risk-to-benefit ratio of this treatment must be reassessed.