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Concept: Mechanical ventilation


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 number, NCT00527813 .).

Concepts: Supine position, Oxygen, Medical statistics, Intensive care medicine, Prone position, Mechanical ventilation, Pulmonology, Acute respiratory distress syndrome


Background Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes. Methods In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause. Results On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P<0.001), and more patients in the HFOV group than in the control group received neuromuscular blockers (83% vs. 68%, P<0.001). In addition, more patients in the HFOV group received vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period than did patients in the control group (5 days vs. 3 days, P=0.01). Conclusions In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality. (Funded by the Canadian Institutes of Health Research; Current Controlled Trials numbers, ISRCTN42992782 and ISRCTN87124254 , and numbers, NCT00474656 and NCT01506401 .).

Concepts: Pulmonary contusion, Clinical trial, Medical statistics, Sample size, Mechanical ventilation, Pulmonology, Intensive care medicine, Acute respiratory distress syndrome


The presence of acute or chronic respiratory failure is often seen as a terminal phase of chronic obstructive pulmonary disease. A great variability in end-of-life practice is observed in these patients mainly because physicians are not always able to correctly predict survival. There is a need for a clear discussion about decision making earlier than when acute respiratory failure ensues. Indeed, a perceived poor quality of life does not necessarily correlate with a clear willingness to refuse invasive or noninvasive mechanical ventilation. It has been suggested to start palliative care earlier, together with curative and restorative care, when there is an increased intensity of symptoms. The patients eligible for palliative care are those complaining of breathlessness, pain, fatigue and depression, which in some studies accounted for a prevalence much higher than 50%. Among comfort measures for palliation, oxygen is frequently prescribed even when the criteria for long-term home oxygen therapy are not met; however, when compared with air, no benefits on dyspnoea have been found. The only drug with a proven effect on dyspnoea is morphine, but not when it is delivered with a nebuliser. Finally, noninvasive ventilation may be used only as a comfort measure for palliation to maximise comfort by minimising adverse effects.

Concepts: Terminal sedation, End-of-life care, Mechanical ventilation, Palliative medicine, Pulmonology, Pneumonia, Palliative care, Chronic obstructive pulmonary disease


The rise in super bugs causing Ventilator-Associated Pneumonia (VAP) is a major cause of mortality and morbidity despite recent advances in management owing to the looming ‘antibiotic apocalypse’. The aetiology and susceptibility pattern of the VAP isolates varies with patient population, type of intensive care unit (ICU) and is an urgent diagnostic challenge. The present study carried out for a period of one year in a tertiary care hospital, enrolled patients on mechanical ventilation (MV) for ≥48 hrs. Endotracheal aspirates (ETA) from suspected VAP patients were processed by semi quantitative method. Staphylococus aureus, members of Enterobacteriaceae were more common in early onset VAP (EOVAP), while Nonfermenting Gram negative bacilli (NFGNB) were significantly associated with late onset VAP (LOVAP). Most of the isolates were multi drug resistant (MDR) super bugs. With limited treatment options left for this crisis situation like the pre-antibiotic era; it is an alarm for rational antibiotic therapy usage and intensive education programs.

Concepts: Tertiary referral hospital, Mechanical ventilation, Gram-negative bacteria, Medicine, Acute respiratory distress syndrome, Ventilator-associated pneumonia, Pneumonia, Antibiotic resistance


General anesthesia is a safe, frequent procedure in clinical practice. Although it is very unusual in procedures not related to head and or neck surgery, vocal cord paralysis is a serious and important complication. Incidence has been associated with patient age and comorbidities, as well as the position of the endotracheal tube and cuff. It can become a dangerous scenario because it predisposes aspiration.

Concepts: General anaesthesia, Phonation, Mechanical ventilation, Pulmonary aspiration, Anesthesia, The Canon of Medicine, Intubation, Endotracheal tube


The adverse effects of mechanical ventilation in acute respiratory distress syndrome (ARDS) arise from two main causes: unphysiological increases of transpulmonary pressure and unphysiological increases/decreases of pleural pressure during positive or negative pressure ventilation. The transpulmonary pressure-related side effects primarily account for ventilator-induced lung injury (VILI) while the pleural pressure-related side effects primarily account for hemodynamic alterations. The changes of transpulmonary pressure and pleural pressure resulting from a given applied driving pressure depend on the relative elastances of the lung and chest wall. The term ‘volutrauma’ should refer to excessive strain, while ‘barotrauma’ should refer to excessive stress. Strains exceeding 1.5, corresponding to a stress above ~20 cmH2O in humans, are severely damaging in experimental animals. Apart from high tidal volumes and high transpulmonary pressures, the respiratory rate and inspiratory flow may also play roles in the genesis of VILI. We do not know which fraction of mortality is attributable to VILI with ventilation comparable to that reported in recent clinical practice surveys (tidal volume ~7.5 ml/kg, positive end-expiratory pressure (PEEP) ~8 cmH2O, rate ~20 bpm, associated mortality ~35%). Therefore, a more complete and individually personalized understanding of ARDS lung mechanics and its interaction with the ventilator is needed to improve future care. Knowledge of functional lung size would allow the quantitative estimation of strain. The determination of lung inhomogeneity/stress raisers would help assess local stresses; the measurement of lung recruitability would guide PEEP selection to optimize lung size and homogeneity. Finding a safety threshold for mechanical power, normalized to functional lung volume and tissue heterogeneity, may help precisely define the safety limits of ventilating the individual in question. When a mechanical ventilation set cannot be found to avoid an excessive risk of VILI, alternative methods (such as the artificial lung) should be considered.

Concepts: Pulmonary contusion, Respiratory physiology, Pneumonia, Intensive care medicine, Thermodynamics, Pulmonology, Mechanical ventilation, Acute respiratory distress syndrome


Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R).

Concepts: Pulmonary contusion, Respiratory physiology, Pneumonia, Carbon dioxide, Oxygen, Mechanical ventilation, Acute respiratory distress syndrome, Pulmonology


A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1β were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced “cytokine storm” at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.

Concepts: Mechanical ventilation, Virus, Cytokine storm, Pneumonia, Influenza, Pulmonology, Cytokine, Acute respiratory distress syndrome


BACKGROUND: Transport of critically ill patients for diagnostic or therapeutic procedures is at risk of complications. Adverse events during transport are common and may have significant consequences for the patient. The objective of the study was to collect prospectively adverse events that occurred during intrahospital transports of critically ill patients and to determine their risk factors. METHODS: This prospective, observational study of intrahospital transport of consecutively admitted patients with mechanical ventilation was conducted in a 38-bed intensive care unit in a university hospital from May 2009 to March 2010. RESULTS: Of 262 transports observed (184 patients), 120 (45.8%) were associated with adverse events. Risk factors were ventilation with positive end-expiratory pressure >6 cmH2O, sedation before transport, and fluid loading for intrahospital transports. Within these intrahospital transports with adverse events, 68 (26% of all intrahospital transports) were associated with an adverse event affecting the patient. Identified risk factors were: positive end-expiratory pressure >6 cmH2O, and treatment modification before transport. In 44 cases (16.8% of all intrahospital transports), adverse event was considered serious for the patient. In our study, adverse events did not statistically increase ventilator-associated pneumonia, time spent on mechanical ventilation, or length of stay in the intensive care unit. CONCLUSIONS: This study confirms that the intrahospital transports of critically ill patients leads to a significant number of adverse events. Although in our study adverse events have not had major consequences on the patient stay, efforts should be made to decrease their incidence.

Concepts: Epidemiology, Hospital, Pneumonia, Mechanical ventilation, Illness, Scientific method, Intensive care medicine, Patient


High-flow nasal cannula oxygen (HFNC) is a relatively new therapy used in adults with respiratory failure. Whether it is superior to conventional oxygen therapy (COT) or to noninvasive mechanical ventilation (NIV) remains unclear. The aim of the present study was to investigate whether HFNC was superior to either COT or NIV in adult acute respiratory failure patients.

Concepts: Emergency medical services, Respiration, Pulmonology, Oxygen therapy, Time, Mechanical ventilation, Nasal cannula, Oxygen