Silvia Coppola

Lung stress and strain during mechanical ventilation: any safe threshold?

RATIONALE Unphysiologic strain (the ratio between tidal volume and functional residual capacity) and stress (the transpulmonary pressure) can cause ventilator-induced lung damage. OBJECTIVES To identify a strain-stress threshold (if any) above which ventilator-induced lung damage can occur. METHODS Twenty-nine healthy pigs were mechanically ventilated for 54 hours with a tidal volume producing a strain between 0.45 and 3.30. Ventilator-induced lung damage was defined as net increase in lung weight. MEASUREMENTS AND MAIN RESULTS Initial lung weight and functional residual capacity were measured with computed tomography. Final lung weight was measured using a balance. After setting tidal volume, data collection included respiratory system mechanics, gas exchange and hemodynamics (every 6 h); cytokine levels in serum (every 12 h) and bronchoalveolar lavage fluid (end of the experiment); and blood laboratory examination (start and end of the experiment). Two clusters of animals could be clearly identified: animals that increased their lung weight (n = 14) and those that did not (n = 15). Tidal volume was 38 ± 9 ml/kg in the former and 22 ± 8 ml/kg in the latter group, corresponding to a strain of 2.16 ± 0.58 and 1.29 ± 0.57 and a stress of 13 ± 5 and 8 ± 3 cm H(2)O, respectively. Lung weight gain was associated with deterioration in respiratory system mechanics, gas exchange, and hemodynamics, pulmonary and systemic inflammation and multiple organ dysfunction. CONCLUSIONS In healthy pigs, ventilator-induced lung damage develops only when a strain greater than 1.5-2 is reached or overcome. Because of differences in intrinsic lung properties, caution is warranted in translating these findings to humans.

Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low‐flow, open atrium and low hematocrit technique. Thirty‐five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X‐ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

Prevalence of endotoxemia after surgery and its association with ICU length of stay

IntroductionThe aim of this observational study was to investigate the prevalence of endotoxemia after surgery and its association with ICU length of stay.Methods102 patients admitted to a university ICU after surgery were recruited. Within four hours of admission, functional data were collected and APACHE II severity score calculated. Arterial blood samples were taken and endotoxemia was measured by chemiluminescence (Endotoxin Activity (EA)). Patients were stratified according to their endotoxin levels (low, intermediate and high) and according to their surgical procedures. Differences between endotoxin levels were assessed by ANOVA, accepting P < 0.05 as significant. Data are expressed as mean ± SD.ResultsEA levels were low in 68 (66%) patients, intermediate in 17 (17%) and high in 17 (17%). Age (61 ± 17 years) and APACHE II score 8.3 ± 3.7 (P = 0.542) were not significantly different in the three EA groups. Functional parameters on admission were similar between EA groups: white blood cells 11093 ± 4605 cells/mm3 (P = 0.385), heart rate 76 ± 16 bpm (P = 0.898), mean arterial pressure 88.8 ± 13.6 mmHg (P = 0.576), lactate 1.18 ± 0.77 mmol/L (P = 0.370), PaO2/FiO2 383 ± 109 mmHg (P = 0.474). Patients with high levels of EA were characterized by longer length of stay in the ICU: 1.9 ± 3.0 days in the low EA group, 1.8 ± 1.4 days in intermediate and 5.2 ± 7.8 days in high group (P = 0.038).Conclusions17% of our patients were characterized by high levels of endotoxemia as assessed by EA assay, despite their low level of complexity on admission. High levels of endotoxin were associated with a longer ICU length of stay.

Extracorporeal Lung Perfusion and Ventilation to Improve Donor Lung Function and Increase the Number of Organs Available for Transplantation

INTRODUCTION Ex vivo lung perfusion (EVLP) has been validated as a valuable technique to increase the pool of organs available for lung transplantation. MATERIAL AND METHODS After a preclinical experience, we obtained permission from the Ethics Committee of our institution to transplant lungs after EVLP reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure (PaO(2))/fraction of inspired oxygen (FiO(2)) ≤ 300 mm Hg were considered to be inclusion criteria, whereas the presence of chest trauma and lung contusion, evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease were exclusion criteria. We only considered subjects on an extra corporeal membrane oxygenation (ECMO) bridge to transplantation with rapid functional deterioration. Using Steen solution with packed red blood cells oxygenated with 21% O(2), 5% to 7% CO(2) was delivered, targeted with a blood flow of approximately 40% predicted cardiac output. Once normothermic, the lungs were ventilated with a tidal volume of 7 mL/kg a PEEP of 5 cmH(2)O and a respiratory rate of 7 bpm. Lungs were considered to be suitable for transplantation if well oxygenated [P(v-a) O(2) > 350 mm Hg on FiO(2) 100%], in the absence of deterioration of pulmonary vascular resistance and lung mechanics over the perfusion time. RESULTS From March to September 2011, six lung transplantations were performed, including two with EVLP. The functional outcomes were similar between groups: at T72 posttransplantation, the median PaO(2)/FiO(2) were 306 mm Hg (range, 282 to 331 mm Hg) and 323 mm Hg (range, 270 to 396 mm Hg) (P = 1, EVLP versus conventional). Intensive care unit ICU and hospital length of stay were similar (P = .533 and P = .663, respectively) with no mortality at 60 days in both groups. EVLP donors were older (49 ± 6 y versus 21 ± 7 y, P < .05), less well oxygenated (184 ± 6 mm Hg versus 570 ± 30, P < .05), displaying higher Oto scores (9.5 ± 0.7 versus 1.7 ± 1.5, P < .05). CONCLUSIONS The first 6 months of the EVLP program allowed us to increase the number of organs available for transplantation with short-term outcomes comparable to conventional transplantations.

β-Adrenergic agonist infusion during extracorporeal lung perfusion: Effects on glucose concentration in the perfusion fluid and on lung function

BACKGROUND We recently showed in a pig model of ex vivo lung perfusion (EVLP) that lung edema correlates with glucose consumption. We investigated whether salbutamol, a β-adrenergic receptor agonist known to upregulate fluid transport in the lung, modulates glucose concentration in the perfusate during EVLP. METHODS Lungs from domestic pigs underwent normothermic EVLP. At the end of controlled reperfusion, lungs were ventilated and perfused for 60 minutes, then randomized to salbutamol (β-Agonist) infusion or placebo (Control) for 180 minutes. Functional parameters were assessed. RESULTS In the β-Agonist group, glucose concentration decreased over time more than corresponding Control values (analysis of variance [ANOVA], p = 0.05). Mean pulmonary artery pressure (mPAP) was 16 ± 1 mm Hg in the β-Agonist group vs 21 ± 1 mm Hg in the Controls (ANOVA p < 0.05). Baseline mPAP was correlated with the drop of mPAP after the β-agonist infusion (R(2) = 0.856, p < 0.05). Dynamic compliance dropped from 51 ± 10 to 31 ± 6 ml/cm H(2)O in the β-Agonist group and from 60 ± 4 to 21 ± 3 ml/cm H(2)O in the Control group (ANOVA, p < 0.05 β-agonist vs Control). The Δ partial pressure of oxygen/fraction of inspired oxygen was 418 ± 15 and 393 ± 12 mm Hg in the β-Agonist and Control groups, respectively (t-test p = 0.106). CONCLUSIONS Glucose concentration in the perfusate was affected by salbutamol. Salbutamol was associated with lower pulmonary pressures and better lung mechanics. These data suggest a possible role for salbutamol as a pharmacologic adjunct during EVLP before transplantation.

Protective lung ventilation during general anesthesia: is there any evidence?

In acute respiratory distress syndrome (ARDS) several studies have shown that mechanical ventilation with high tidal volume (VT) and low levels of positive end-expiratory pressure (PEEP) can promote ventilator-induced lung injury (VILI), thus increasing morbidity and mortality [1]. An open lung strategy, combining the use of low VT with adequate PEEP levels and recruitment maneuvers, has thus been recommended in ARDS patients [2–4]. In patients without ARDS admitted to intensive care units (ICUs), who required mechanical ventilation for at least 12 hours, the use of a high VT significantly increased the inflammatory response [5, 6]. In contrast to critically ill patients, during general anesthesia, mechanical ventilation is required only for a few hours, thus the beneficial effects of lung-protective ventilation remain questionable. Moreover, there are limited data from few randomized controlled trials with only small cohorts of enrolled patients.

What's Next After ARDS: Long-Term Outcomes

ARDS is a life-threatening organ failure due to several pulmonary and extrapulmonary injuries with an incidence between 5 and 60 cases/100,000 persons/y. Patients with ARDS have non-cardiogenic pulmonary edema and dyspnea often requiring invasive mechanical ventilation and intensive care admission. Although the short-term mortality rate has significantly decreased in the last decade, mainly due to the widespread application of lung-protective ventilation and better general support, long-term outcomes are still unsatisfactory. Besides simply evaluating the outcome at hospital discharge, several recent studies have assessed the health-related quality of life, neuropsychological disability, radiological findings, and pulmonary dysfunction up to 5 y. This paper reviews the literature regarding the long-term outcomes in patients with ARDS.

Sodium bicarbonate treatment during transient or sustained lactic acidemia in normoxic and normotensive rats.

Introduction Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of lactic acidemia per se without the confounding factor of an underlying organic cause of acidosis. Methodology Sprague Dawley rats underwent a primed endovenous infusion of L(+) lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n = 8 per group): S) sustained infusion of lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzymes activity were also measured. Principal Findings Following lactic acid infusion blood lactate rose (P<0.05), pH (P<0.05) and strong ion difference (P<0.05) drop. Some rats developed hemodynamic instability during the primed infusion of lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of lactic acid (from 7.22±0.02 to 7.36±0.04, P<0.05) while overshoot to alkalemic values when the infusion was transient (from 7.24±0.01 to 7.53±0.03, P<0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P<0.05) so that blood lactate was higher (2.9±1 mmol/l vs. 1.0±0.2, P<0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2 = 0.475, P<0.05). Conclusions pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load.

β-blockers in critically ill patients: from physiology to clinical evidence

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Fluid resuscitation in trauma patients: what should we know?

Purpose of reviewFluid resuscitation in trauma patients could reduce organ failure, until blood components are available and hemorrhage is controlled. However, the ideal fluid resuscitation strategy in trauma patients remains a debated topic. Different types of trauma can require different types of fluids and different volume of infusion. Recent findingsThere are few randomized controlled trials investigating the efficacy of fluids in trauma patients. There is no evidence that any type of fluids can improve short-term and long-term outcome in these patients. The main clinical evidence emphasizes that a restrictive fluid resuscitation before surgery improves outcome in patients with penetrating trauma. Fluid management of blunt trauma patients, in particular with coexisting brain injury, remains unclear. SummaryIn order to focus on the state of the art about this topic, we review the current literature and guidelines. Recent studies have underlined that the correct fluid resuscitation strategy can depend on the type of trauma condition: penetrating, blunt, brain injury or a combination of them. Of course, further studies are needed to investigate the impact of a specific fluid strategy on different type and severity of trauma.