Pierpaolo Terragni

Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.

Objectives:To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. Design:Matched cohort study with historical control. Setting:Two academic Italian ICUs. Patients:Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). Interventions:Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ⩽ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. Measurements and Main Results:Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07–0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5–31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6–57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. Conclusions:These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

Role and potentials of low-flow CO2 removal system in mechanical ventilation.

Purpose of reviewAn analysis of the technological implementation of extracorporeal CO2 removal (ECCO2R) techniques and of its clinical application. A new classification of ECCO2R, based on technological aspects, clinical properties and physiological performance, is proposed. Recent findingsThe use of a ventilation with lower tidal volumes has been proved successful in acute respiratory distress syndrome (ARDS) patients but can be extremely problematic, especially when dealing with respiratory acidosis. The implementation of ECCO2R devices can represent the missing link between the prevention of ventilator-induced lung injury and pH control. ECCO2R has attracted increasing interest because of new less-invasive approaches allowing an easier management of ARDS patients. Recent studies have also shown that ECCO2R can also be used in patients with exacerbation of chronic obstructive pulmonary disease (COPD) and as a bridge to lung transplantation. SummaryThe future ventilatory management of patients with acute respiratory failure may include a minimally invasive extracorporeal carbon dioxide removal circuit associated with the least amount of ventilatory support (noninvasive in COPD and/or invasive in ARDS) to minimize sedation, prevent ventilator-induced acute lung injury and nosocomial infections. Randomized clinical trials in the pipeline will confirm this fascinating hypothesis.

Physiological effects of an open lung ventilatory strategy titrated on elastance-derived end-inspiratory transpulmonary pressure: Study in a pig model*

Rationale:In the presence of increased chest wall elastance, the airway pressure does not reflect the lung-distending (transpulmonary) pressure. Objective:To compare the physiological effects of a conventional open lung approach titrated for an end-inspiratory airway opening plateau pressure (30 cm H2O) with a transpulmonary open lung approach titrated for a elastance-derived end-inspiratory plateau transpulmonary pressure (26 cm H2O), in a pig model of acute respiratory distress syndrome (HCl inhalation) and reversible chest wall mechanical impairment (chest wall and abdomen restriction). Methods:In eight pigs, physiological parameters and computed tomography were recorded under three conditions: 1) conventional open lung approach, normal chest wall; 2) conventional open lung approach, stiff chest wall; and 3) transpulmonary open lung approach, stiff chest wall. Measurements and Main Results:As compared with the normal chest wall condition, at end-expiration non aerated lung tissue weight was increased by 116 ± 68 % during the conventional open lung approach and by 28 ± 41 % during the transpulmonary open lung approach (p < .01), whereas cardiac output was decreased by 27 ± 19 % and 22 ± 14 %, respectively (p = not significant). Conclusion:In this model, the end-inspiratory transpulmonary open lung approach minimized the impact of chest wall stiffening on alveolar recruitment without causing hemodynamic impairment.

Extracorporeal membrane oxygenation in adult patients with acute respiratory distress syndrome.

Purpose of reviewTo examine the role of extracorporeal membrane oxygenation (ECMO) as potential therapeutic option for severe cases of acute respiratory distress syndrome (ARDS). Recent findingsThe use of ECMO to treat acute respiratory failure dramatically increased. Factors that may explain this increase in the use of ECMO are H1N1 pandemic influenza, results of recent clinical trials and not lastly the technological development and consequently the commercial pressure of the industry. Under these circumstances, clinicians urgently need clinical trials and formal indication, contraindication and rules for implementation to provide reproducible results. SummaryGuidelines from the Extracorporeal Life Support Organization still indicate ECMO for acute severe pulmonary failure potentially reversible and unresponsive to conventional management. The new definition of ARDS (Berlin definition) addresses clinicians to the best treatment options in respect of the severity of illness and allocates ECMO as a potential therapeutic option for patients with severe ARDS and a P/F ratio lower than 100 and proposed that the indication of ECMO may be shifted from the treatment of choice for refractory hypoxemia to the treatment of choice to minimize ventilator-induced lung injury.

Novel approaches to minimize ventilator-induced lung injury

Purpose of reviewTo discuss the mechanisms of ventilator-induced lung injury and the pro and cons of the different approaches proposed by literature to minimize its impact in patients with acute respiratory distress syndrome. Recent findingsMechanical ventilation is indispensable to manage respiratory failure. The evolution of knowledge of the physiological principles and of the clinical implementation of mechanical ventilation is characterized by the shift of interest from its capability to restore ‘normal gas exchange’ to its capability of causing further lung damage and multisystem organ failure. SummaryIf one of the essential teachings to young intensivists in the 1980s was to ensure mechanical ventilation restored being able to immediately drain a pneumothorax (barotrauma), nowadays priority we teach to young intensivists is to implement ‘protective’ ventilation to protect the lungs from the pulmonary and systemic effects of ventilator-induced lung injury (biotrauma). At the same time, priority of clinical research shifted from the search of optimal ventilator settings (best positive end-expiratory pressure) and to the evaluation of ‘super-protective’ ventilation that integrating partial or total extracorporeal support tries to minimize the use of mechanical ventilation.

Combination antifungal treatment of pseudomembranous tracheobronchial invasive aspergillosis: a case report.

Invasive aspergillosis (IA) is increasingly recognized in the intensive care unit (ICU), and new risk factors associated with respiratory colonization or infection by Aspergillus spp. include steroid treatment and chronic lung obstructive disease [1, 2]. In a review of 289 autopsies in the ICU, IA was the leading cause of Goldman class I discrepancy (a missed major diagnosis with major impact on patient management and survival) [3]. The epidemiology of IA indicates an increasing number of infections in immunosuppressed patients/individuals undergoing transplantation of bone marrow, hematopoietic stem cells, or organ transplantations, and those receiving intensive chemotherapy or other immunosuppressive treatments. A broad group of patients who are admitted to ICU also have some form of immunosupppression and may be susceptible to invasive mould infections. For various reasons, figures about the true incidence of IA in ICU are difficult to generate. The most important reason is the difficulty encountered in making a definite diagnosis of IA (lack of sensitivity and specificity with regard to culture and radiology) [4]. Recently, galactomannan (GM) in bronchoalveolar lavage (BAL) fluid appears to be a promising tool for early diagnosis in non-neutropenic critically ill patients and has been associated in proven cases with sensitivity and specificity of 88 and 87%, respectively [5]. Pseudomembranous and obstructive Aspergillus tracheobronchitis are still considered to have a fatal outcome and have been reported in a wide variety of patients [6]. There has been only one report in a patient with diabetes which was treated by deoxycholate amphotericin B (AmB) and subsequent addition of oral itraconazole [7]. In this paper, we report a pseudomembranous and obstructive tracheobronchitis in a diabetic patient successfully treated with caspofungin and AmB.

Independent high-frequency oscillatory ventilation in the management of asymmetric acute lung injury.

We present a case of independent lung ventilation in an adult with asymmetric acute lung injury. We applied a conventional protective ventilatory strategy to the more homogeneously infiltrated lung and high-frequency oscillatory ventilation to the almost totally collapsed lung, because a conventional protective strategy exposed this lung to plateau pressure more than 30 cm H2O, whereas high-frequency oscillatory ventilation provided sufficient gas exchange at safer pressure levels. Analysis of a lung computed tomography scan was used to evaluate the efficacy of the ventilatory strategy.

Accuracy of esophageal pressure to assess transpulmonary pressure during mechanical ventilation

The difference in pressure inside (airway pressure) minus outside (pleural pressure) the lungs represents transpulmonary pressure. Esophageal pressure (PES) is a surrogate for pleural pressure but controversies exist on how derive the values of PES to calculate transpulmonary pressure [1, 2]. Ex vivo lung perfusion (EVLP) followed by transplant may allow the comparison of transpulmonary pressure values obtained outside the thorax with the values obtained from the same lungs inside the thorax after transplantation [3]. We identified the method to derive PES values that provide the best agreement between “in vivo” and “ex vivo” assessment of transpulmonary. Institutional review board approved the study and written informed consent was obtained from transplanted patients. Lungs referred for EVLP and patients receiving bilateral transplant were included. Measurements were performed if the best PaO2/FiO2 during 4 h of EVLP was ≥350 [3] and if patients had a PaO2/FiO2 ≥ 350 with a level of PEEP ≤ 10 cmH2O. Patients were excluded and measurement not performed in the presence of pleural effusion at chest X-ray, if ECMO or a chest tube was needed, if PaO2/FiO2 < 350, or PEEP > 10 cmH2O. “Ex vivo” and “in vivo” measurements were performed with a respiratory rate of 7 breaths/min, a tidal volume of 10 ml/kg donor PBW, and an FiO2 of 1.0 [3]. “In vivo” measurements were obtained in the semi-recumbent position and 24 h after ICU admission. To match lung volume between “ex vivo” and “in vivo”, PEEP was set at 5 cmH2O in the former and 0 cmH2O in the latter [4]. Transpulmonary pressures at end-inspiration and endexpiration were calculated using values of PES referred to atmosphere (PES_ABSOLUTE), or assuming that pleural pressure is 5 cmH2O lower than PES_ABSOLUTE (PES_CORRECTED), or referring PES to the value at end-expiration ∆PES [1]. Elastance of the lung (EstL) was calculated [1, 2]. Inferential analysis was based on the computation of the two-tailed 95 % confidence intervals (CI) of the mean (one-sample t distribution) of the differences between alternative methods. Measurements were performed in 15 cases. PES_ABSOLUTE and PES_CORRECTED provided the best agreement between “in vitro” and “in vivo” measurements of EstL. The best agreement between “ex vivo” and “in vivo” values of end-inspiratory and end-expiratory transpulmonary pressure was observed using PES_CORRECTED. On the other hand, the way how values of transpulmonary pressure were derived from esophageal pressure had little impact on the result of EstL as this calculation is based on the difference between end-inspiratory and end-expiratory transpulmonary pressures (Table 1). Our study has the following limitations: (a) although “ex vivo” and “in vivo” PaO2/FiO2 values were similar (444 ± 70 vs. 432 ± 64, respectively) these conditions are very different and the time between the two measurements of transpulmonary pressure is relatively long; (b) we did not assess absolute lung volumes; (c) the correction factor to calculate was fixed at 5 cmH2O [1] but other studies showed it may vary among subjects [5]. *Correspondence: pterragni@uniss.it; pierpaolo.terragni@aousassari.it 1 Department of Surgical Sciences Anesthesia and General Intensive Care, Università di Sassari, Viale San Pietro 43, (07100) Sassari, Italy Full author information is available at the end of the article

Extracorporeal CO2 Removal May Improve Renal Function of Patients with ARDS and Acute Kidney Injury

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A fixed correction of absolute transpulmonary pressure may not be ideal for clinical use

Initial correspondence from Dr. Baedorf Kassis et al. Dear Editor, We read with interest the letter by Terragni [1] describing a marvelous experiment before and after lung transplantation which suggested that pleural pressure is 5 cmH2O lower than esophageal pressure (Pes). We have made similar estimates based on the 3–7 cmH2O increase in Pes moving from upright to supine, but there is considerable variation among individuals [2]. As explained by the authors, ideally transpulmonary pressure (PL) would have been related to lung size before and after transplantation, as elastance may not be a sensitive indicator of inflation. More importantly, the magnitude of the best correction (5 cmH2O) in this study may have been largely determined by the positive end expiratory pressure (PEEP) difference between ex vivo and in vivo measurements. For example, if PEEP applied ex vivo had been 10 instead of 5 cmH2O, the optimal correction would likely have been greater than 5 cmH2O. Overestimation of pleural pressure by ~5 cmH2O using Pes leads to a similar underestimation of PL, so an endexpiratory PL of zero gives a functional PL of 5 cmH2O. With this in mind, clinical trials using Pes to guide clinical decisions such as the forthcoming EPvent2 study [3] have avoided choosing a specific correction value, recognizing inter-individual variation and uncertainty in this relationship [2]. While we admire the elegance of Terragni’s study and are excited to see further work, the use of Pes in estimating transpulmonary pressure and parenchymal stress must be understood in the context of these uncertainties, and we are cautious about over-interpretation and clinical application.