Evidence of Air Trapping During Ex Vivo Lung Perfusion: A Swine Experimental Lung Imaging and Mechanics Study.

Ex vivo lung perfusion (EVLP) allows the ventilation and perfusion of lungs to evaluate their viability for transplantation. The aim of this study is to compare the mechanical, morphologic and functional properties of lungs during EVLP with values obtained in vivo to guide a safe mechanical ventilation strategy. Lungs from 5 healthy pigs were studied in vivo and during 4 hours of EVLP. Lung compliance, airway resistance, gas exchange, and hemodynamic parameters were collected at positive end-expiratory pressure (PEEP) of 5 cm H2O. Computed tomography was performed at PEEP 0, PEEP 5, and total lung capacity (TLC). Lung pressure-volume (PV) curves were performed from PEEP 0 to TLC. Lung compliance decreased during EVLP (53 ± 5 mL/cm H2O vs 29 ± 7 mL/cm H2O, P < .05), and the PV curve showed a lower inflection point. Gas content (528 ± 118 mL vs 892 ± 402 mL at PEEP 0) and airway resistance (25 ± 5 vs 44 ± 9 cmH2O/L∗s-1, P < .05) were higher during EVLP. Alveolar dead space (5% ± 2% vs 17% ± 6%, P < .05) and intrapulmonary shunt (9% ± 2% vs 28% ± 13%, P < .05) increased ex vivo compared to in vivo, while the partial pressure of oxygen to inspired oxygen fraction ratio (PO2/FiO2) did not differ (468 ± 52 mm Hg vs 536 ± 14 mm Hg). In conclusion, during EVLP lungs show signs of air trapping and bronchoconstriction, resulting in low compliance and increased alveolar dead space. Intrapulmonary shunt is high despite oxygenation levels acceptable for transplantation.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure. METHODS: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods. RESULTS: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use. CONCLUSION: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

Ventilation during extracorporeal support : Why and how.

The main target of extracorporeal support is to achieve viable gas exchange, while minimizing the risk of ventilator-induced lung injury, achieved through a decreased mechanical ventilation load on the natural lung. However, during veno-venous extracorporeal membrane oxygenation (ECMO), mechanical ventilation is still necessary in order to prevent lung collapse and/or if extracorporeal blood flow is not sufficient to guarantee adequate gas exchange. In this review, we will summarize the physiology of extracorporeal support and the rationale for continuing mechanical ventilation in this context. Furthermore, we will review the current clinical practice among ECMO centers and their suggestions regarding mechanical ventilator settings. While optimal ventilatory settings are still a matter of debate, the use of a strategy combining low tidal volume and limited inspiratory pressures is accepted worldwide. On the contrary, the choice of applied positive end-expiratory pressure (PEEP) varies between the total rest strategy and open lung strategy. Finally, the use of assisted or spontaneous ventilation will be discussed.

A novel risk score for severe ARDS patients undergoing ECMO after retrieval from peripheral hospitals.

BACKGROUND: Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to conventional protective ventilation is associated with elevated costs, resource and complications, and appropriate risk stratification of candidate patients could be useful to recognize those more likely to benefit from ECMO. We aimed to derive a new outcome prediction score for patients retrieved by our ECMO team from peripheral centers, including systematic echocardiographic evaluation before ECMO start. METHODS: Sixty-nine consecutive patients with refractory ARDS requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO referral center), from 1 October 2009 to 31 December 2015, were assessed. RESULTS: All patients were transported on ECMO (distance, median 77, range 4-456 km) The mortality rate was 41% (28/69). Our new risk score included age ≥ 42 years, BMI < 31 kg/m2 , RV dilatation, and pH < 7.35. The proposed cut off (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30% (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P < 0.001). When assessing the discriminatory ability of our risk score in the population of local patients, survivors had a mean value of 15.4 ± 8.6, whereas non-survivors showed a mean value of 20.1 ± 7.4 (P < 0.001). CONCLUSIONS: Our new risk score shows good discriminatory ability both in patients retrieved from peripheral centers and in those implanted at our center. This score includes variables easily available at bedside, and, for the first time, a pathophysiologic element, RV dilatation.

An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome

BACKGROUND: This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. RESULTS: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4-8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS. CONCLUSIONS: The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.

Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion.

We developed a protocol to procure lungs from uncontrolled donors after circulatory determination of death (NCT02061462). Subjects with cardiovascular collapse, treated on scene by a resuscitation team and transferred to the emergency room, are considered potential donors once declared dead. Exclusion criteria include unwitnessed collapse, no-flow period of >15 min and low flow >60 min. After death, lung preservation with recruitment maneuvers, continuous positive airway pressure, and protective mechanical ventilation is applied to the donor. After procurement, ex vivo lung perfusion (EVLP) is performed. From November 2014, 10 subjects were considered potential donors; one of these underwent the full process of procurement, EVLP, and transplantation. The donor was a 46-year-old male who died because of thoracic aortic dissection. Lungs were procured 4 h and 48 min after death, and deemed suitable for transplantation after EVLP. Lungs were then offered to a rapidly deteriorating recipient with cystic fibrosis (lung allocation score [LAS] 46) who consented to the transplant in this experimental setting. Six months after transplantation, the recipient is in good condition (forced expiratory volume in 1 s 85%) with no signs of rejection. This protocol allowed procurement of lungs from an uncontrolled donor after circulatory determination of death following an extended period of warm ischemia.

Multimodal neurological approach can lead the treatment in postcardiac arrest persistent refractory status epilepticus.

Refractory status epilepticus (RSE) is a common challenge in the setting of post resuscitation care. We describe how multimodal neurological approach can lead treatment and improve the prognosis. We report on three survivors of cardiac arrest (CA) who had good neurological outcomes after mild hypothermia (TH), despite exhibiting persisting RSE requiring treatment with several antiepileptic (AED) and anesthetic drugs, including barbiturate-induced coma. No evidence-based data exist to guide management of RSE in the setting of anoxic brain injury. Our cases emphasize the need for continuous active treatment led by a multimodal approach in order to improve neurological outcome.

Efficacy, safety and acceptability of the new pen needle 33G × 4 mm. AGO 01 study.

OBJECTIVES: Adherence to insulin therapy can be threatened by pain and needle fear. This cross-over randomized non-inferiority trial evaluated a new Pic Insupen 33G × 4 mm needle vs. a 32G × 4 mm needle in terms of metabolic control, safety and acceptability in patients with diabetes treated with insulin. RESEARCH DESIGN AND METHODS: We used a centralized, permuted block randomization, stratified by center and maximum insulin dose per single injection. Subjects used the two needles in two 3 week treatment periods. The primary endpoint was the absolute percentage variation of the blood fructosamine between the two treatments (% |ΔFru|). Additional endpoints were: glycemic variability, total insulin doses, body weight, severe hypoglycemic episodes, leakage at injection sites and pain measured by visual analogue scale. Equivalent glycemic control was defined a priori as % |ΔFru| (including 95% CI) within 20%. RESULTS: Of 87 subjects randomized, 77 completed the study (median age 53.1 [IR 42.3-61.2], median BMI 24.3 Kg/m(2) [IR 21.3-28.5], median duration of insulin therapy [in months] 141.4 (IR 56.3-256.9), median baseline HbA1c 7.9% [IR 7.2-8.8]). The % |ΔFru| was 7.93% (95% CI 6.23-9.63), meeting the non-inferiority criterion. The fasting blood glucose standard deviation was 46.2 (mean 154.6) with the 33G needle and 42.8 (mean 157.3) with the 32G needle (p=0.42). Insulin daily dose and patients' weight did not show any statistically significant variation. We observed 95 episodes of symptomatic hypoglycemia with the 33G needle and 96 with the 32G needle. One episode of severe hypoglycemia was documented in the latter group. As for insulin leakage we observed 37.55 episodes per 100 patient-days with the 33G needle and 32.21 episodes per 100 patient-days with the 32G needle (p=0.31). Patients reported less pain with the 33G × 4 mm needle (p=0.05). STUDY LIMITATIONS: Study sample was mainly composed of adults with type 1 diabetes and study was not blinded. CONCLUSIONS: The 33G needle is not inferior to the 32G needle in terms of efficacy and safety, with reduced pain and no difference in insulin leakage. CLINICAL TRIAL REGISTRATION: NCT01745549.

Outbreak of skin and soft tissue infections in a hospital newborn nursery in Italy due to community-acquired meticillin-resistant Staphylococcus aureus USA300 clone.

BACKGROUND: Community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) is responsible for severe infections in previously healthy people acquired in the community in different areas of the world. AIM: To report an outbreak of CA-MRSA in a hospital newborn nursery in northern Italy in September-October 2010, its investigation and control measures. METHODS: The epidemiology of the outbreak is reported. The investigation included screening neonates, parents and staff for MRSA carriage. Molecular strain typing was performed on MRSA isolates. FINDINGS: The outbreak affected nine neonates with three severe infections. In addition, four mothers had postpartum mastitis, and three mothers and one father had skin infection. The outbreak strain belonged to the USA300 CA-MRSA clone. Asymptomatic carriage of the outbreak strain was found among neonates, parents and hospital staff. The implementation of appropriate infection control measures in the hospital terminated the outbreak. CONCLUSIONS: To our knowledge, this is the first report of a hospital outbreak caused by the USA300 CA-MRSA clone in Europe. It is important to reinforce infection control measures, particularly in high-risk groups, such as neonates, to prevent USA300 from becoming endemic in European hospitals.

Performance of different PEEP valves and helmet outlets at increasing gas flow rates: a bench top study.

BACKGROUND: Aim of the paper was to assess the performance of different expiratory valves and the resistance of helmet outlet ports at increasing gas flow rates. METHODS: A gas flow-meter was connected to 10 different expiratory peep valves: 1 water-seal valve, 4 precalibrated fixed PEEP valves and 5 adjustable PEEP valves. Three new valves of each brand, set at different pressure levels (5-7.5-10-12.5-15 cmH(2)O, if available), were tested at increasing gas flow rates (from 30 to 150 L/min). We measured the pressure generated just before the valves. Three different helmets sealed on a mock head were connected at the inlet port with a gas flow-meter while the outlet was left clear. We measured the pressure generated inside the helmet (due to the flow-resistance of the outlet port) at increasing gas flow rates. RESULTS: Adjustable valves showed a variable degree flow-dependency (increasing difference between the measured and the expected pressure at increasing flow rates), while pre-calibrated valves revealed a flow-independent behavior. Water seal valve showed low degree flow-dependency. The pressures generated by the outlet port of the tested helmets ranged from 0.02 to 2.29 cmH(2)O at the highest gas flow rate. CONCLUSION: Adjustable PEEP valves are not suggested for continuous-flow CPAP systems as their flow-dependency can lead to pressures higher than expected. Precalibrated and water seal valves exhibit the best performance. Different helmet outlet ports do not significantly affect the pressure generated during helmet CPAP. In order to avoid iatrogenic complications gas flow and pressure delivered during helmet CPAP must always be monitored.

Long-term extracorporeal membrane oxygenation with minimal ventilatory support: a new paradigm for severe ARDS?

Pulmonary tuberculosis can lead to acute respiratory distress syndrome (ARDS) which is associated with high mortality. We report the case of a patient with pulmonary tuberculosis and severe ARDS (PaO2/FiO2<100 mmHg) who was initially managed with advanced up-to-date treatments (protective ventilation and extracorporeal membrane oxygenation, ECMO) but failed to improve. After a month of failure and the development of bilateral pneumothoraces, we drastically changed our therapeutic strategy: we maximized ECMO support to maintain oxygenation, we greatly reduced ventilation pressures and we left the pneumothoraces undrained. From then on, the patient improved and he eventually survived. This case suggests that ECMO permits large reductions in lung inflation and ventilation to rest the lungs, while maintaining acceptable oxygenation. The combination of ECMO and markedly attenuated ventilation strategy may be effective in cases of severe ARDS.

Management of acute respiratory complications from influenza A (H1N1) infection: experience of a tertiary-level Intensive Care Unit.

BACKGROUND: The novel influenza A (H1N1) pandemic was associated with an epidemic of critical illness. METHODS: We describe the clinical profiles of critically ill patients with severe complications due to microbiologically confirmed pandemic influenza A (H1N1) infection admitted to a medical ICU in Monza, Italy, over a 6-month period. RESULTS: From August 2009 to January 2010, 19 patients (13 adults and 6 children) required ICU admission. Nine subjects were referred to our hospital from other ICUs. In all patients, with the exception of a case of severe septic shock, the cause of ICU admission was acute respiratory failure. Other nonpulmonary organ failures were common. A trial of non-invasive ventilation was attempted in 13 cases and was successful in four of them. The majority of the patients required invasive mechanical ventilation. In the 7 most severely hypoxemic patients, we applied veno-venous ECLS, with a very high rate of success. The median ICU stay was 9 days (range 1-78 days). Sixteen out of 19 (84%) patients survived. CONCLUSION: In the majority of our patients, critical illness caused by pandemic influenza A (H1N1) was associated with severe hypoxemia, multiple organ failure, requirement for mechanical ventilation and frequent use of rescue therapies and ECLS support.

Positron emission tomography in ARDS: a new look at an old syndrome.

This is a review of some of the main findings obtained by positron emission tomography (PET) concerning the pathophysiology of acute respiratory distress syndrome (ARDS) and acute lung injury. PET (which is nowadays often combined with computed tomography) is a functional imaging technique based on the detection of a labeled molecule administered to a subject. Based on the molecule used, different lung functions can be imaged. Examples include inhaled, labeled nitrogen, which allows us to visualize regional aeration and ventilation, whereas lung perfusion has been studied by means of labeled water or by injected nitrogen dissolved in saline. With this latter technique, a global assessment of regional gas exchange is possible. Administration of [18F]FDG facilitates the imaging of cellular metabolic activity, reflecting an acute neutrophil-sustained inflammatory process. This technique has been used in experimental ARDS and, more recently, in patients. It showed, for example, that inflammatory activity of the lungs is markedly increased even in "normally aerated" regions at levels that are, in some cases, even higher than in the non-aerated regions.

Etiology of respiratory failure is related to mortality in critically ill patients affected by a hematological malignancy: a retrospective study.

AIM: The outcomes of patients affected by hematologic malignancies (HM) admitted to Intensive Care Units (ICUs) because of life-threatening complications are still considered to be poor. The aim of this study was to assess the incidence and impact of cardiac dysfunction on the outcome of these patients. METHODS: We retrospectively reviewed the records of the 48 patients (both adult and pediatric) with HM admitted in our ICU over the last four years, collecting data on admission diagnosis, type of HM, laboratory values and organ failure. RESULTS: All patients were admitted with respiratory failure. The overall mortality rate was 50% and the mortality rates were similar among patients with different types of HM. Septic shock and multiple organ failure were the leading causes of death. The overall incidence of cardiac dysfunction was high (31%). Interestingly, the ICU mortality of this subgroup was 27%, while the mortality of the rest of the population was 61% (p<0.05). CONCLUSIONS: ICU patients with HM have high mortality. Respiratory failure caused by cardiac dysfunction seems to be associated with a lower risk of death.

A case of ARDS associated with influenza A - H1N1 infection treated with extracorporeal respiratory support.

After the first outbreak identified in Mexico in late March 2009, influenza A sustained by a modified H1N1 virus ("swine flu") rapidly spread to all continents. This article describes the first Italian case of life-threatening ARDS associated with H1N1 infection, treated with extracorporeal respiratory assistance (venovenous extracorporeal membrane oxygenation [ECMO]). A 24-year-old, previously healthy man was admitted to the Intensive Care Unit (ICU) of the local hospital for rapidly progressive respiratory failure with refractory impairment of gas exchange unresponsive to rescue therapies (recruitment manoeuvres, pronation and nitric oxide inhalation). An extracorporeal respiratory assistance (venovenous ECMO) was performed. It allowed a correction of the respiratory acidosis and made possible the transportation of the patient to the ICU (approximately 150 km from the first hospital). A nasal swab tested positive for H1N1 infection and treatment with oseltamivir was started. The chest computed tomography scan showed bilateral massive, patchy consolidation of lung parenchyma; lab tests showed leukopenia, elevated CPK levels and renal failure. The patient required high dosages of norepinephrine for septic shock and continuous renal replacement therapy. The clinical course was complicated by Pseudomonas aeruginosa superinfection, treated with intravenous and aerosolised colistin. ECMO was withheld after 15 days, while recovery of renal and respiratory function was slower. The patient was discharged from the ICU 34 days after admission. In this case, ECMO was life-saving and made the inter-hospital transfer of the patient possible.