Acute liver failure.

PURPOSE OF REVIEW: Present an outline of acute liver failure, from its definition to its management in critical care, updated with findings of selected newer research. RECENT FINDINGS: Survival of patients with acute liver failure has progressively improved. Intracranial hypertension complicating hepatic encephalopathy is now much less frequent than in the past and invasive ICP monitoring is now rarely used. Early renal replacement therapy and possibly therapeutic plasma exchange have consolidated their role in the treatment. Further evidence confirms the low incidence of bleeding in these patients despite striking abnormalities in standard tests of coagulation and new findings of abnormalities on thromboelastographic testing. Specific coagulopathy profiles including an abnormal vWF/ADAMTS13 ratio may be associated with poor outcome and increased bleeding risk. Use of N-acetylcysteine in nonparacetamol-related cases remains unsupported by robust clinical evidence. New microRNA-based prognostic markers to select patients for transplantation are described but are still far from widespread clinical applicability; imaging-based prognostication tools are also promising. The use of extracorporeal artificial liver devices in clinical practice is yet to be supported by evidence. SUMMARY: Medical treatment of patients with acute liver failure is now associated with significantly improved survival. Better prognostication and selection for emergency liver transplant may further improve care for these patients.

Bedside noninvasive monitoring of mechanically ventilated patients.

PURPOSE OF REVIEW: Among noninvasive lung imaging techniques that can be employed at the bedside electrical impedance tomography (EIT) and lung ultrasound (LUS) can provide dynamic, repeatable data on the distribution regional lung ventilation and response to therapeutic manoeuvres.In this review, we will provide an overview on the rationale, basic functioning and most common applications of EIT and Point of Care Ultrasound (PoCUS, mainly but not limited to LUS) in the management of mechanically ventilated patients. RECENT FINDINGS: The use of EIT in clinical practice is supported by several studies demonstrating good correlation between impedance tomography data and other validated methods of assessing lung aeration during mechanical ventilation. Similarly, LUS also correlates with chest computed tomography in assessing lung aeration, its changes and several pathological conditions, with superiority over other techniques. Other PoCUS applications have shown to effectively complement the LUS ultrasound assessment of the mechanically ventilated patient. SUMMARY: Bedside techniques - such as EIT and PoCUS - are becoming standards of the care for mechanically ventilated patients to monitor the changes in lung aeration, ventilation and perfusion in response to treatment and to assess weaning from mechanical ventilation.

A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID-19).

Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O2 ) affinity. Calculated oxygen tension at half-saturation (p50 ) was on average (±SD) 3·3 (3·13) mmHg lower than the normal p50 value (23·4 vs. 26·7 mmHg; P < 0·0001). Compared to an unmatched historic control of patients with other causes of severe respiratory failure, patients with COVID-19 had a significantly higher Hb-O2 affinity (mean [SD] p50 23·4 [3·13] vs. 24·6 [5.4] mmHg; P < 0·0001). We hypothesise that, due to the long disease process, acclimatisation to hypoxaemia could play a role.

Extracorporeal Membrane Oxygenation for Respiratory Failure.

This review focuses on the use of veno-venous extracorporeal membrane oxygenation for respiratory failure across all blood flow ranges. Starting with a short overview of historical development, aspects of the physiology of gas exchange (i.e., oxygenation and decarboxylation) during extracorporeal circulation are discussed. The mechanisms of phenomena such as recirculation and shunt playing an important role in daily clinical practice are explained.Treatment of refractory and symptomatic hypoxemic respiratory failure (e.g., acute respiratory distress syndrome [ARDS]) currently represents the main indication for high-flow veno-venous-extracorporeal membrane oxygenation. On the other hand, lower-flow extracorporeal carbon dioxide removal might potentially help to avoid or attenuate ventilator-induced lung injury by allowing reduction of the energy load (i.e., driving pressure, mechanical power) transmitted to the lungs during mechanical ventilation or spontaneous ventilation. In the latter context, extracorporeal carbon dioxide removal plays an emerging role in the treatment of chronic obstructive pulmonary disease patients during acute exacerbations. Both applications of extracorporeal lung support raise important ethical considerations, such as likelihood of ultimate futility and end-of-life decision-making. The review concludes with a brief overview of potential technical developments and persistent challenges.

Does Iso-mechanical Power Lead to Iso-lung Damage?: An Experimental Study in a Porcine Model.

BACKGROUND: Excessive tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) are all potential causes of ventilator-induced lung injury, and all contribute to a single variable: the mechanical power. The authors aimed to determine whether high tidal volume or high respiratory rate or high PEEP at iso-mechanical power produce similar or different ventilator-induced lung injury. METHODS: Three ventilatory strategies-high tidal volume (twice baseline functional residual capacity), high respiratory rate (40 bpm), and high PEEP (25 cm H2O)-were each applied at two levels of mechanical power (15 and 30 J/min) for 48 h in six groups of seven healthy female piglets (weight: 24.2 ± 2.0 kg, mean ± SD). RESULTS: At iso-mechanical power, the high tidal volume groups immediately and sharply increased plateau, driving pressure, stress, and strain, which all further deteriorated with time. In high respiratory rate groups, they changed minimally at the beginning, but steadily increased during the 48 h. In contrast, after a sudden huge increase, they decreased with time in the high PEEP groups. End-experiment specific lung elastance was 6.5 ± 1.7 cm H2O in high tidal volume groups, 10.1 ± 3.9 cm H2O in high respiratory rate groups, and 4.5 ± 0.9 cm H2O in high PEEP groups. Functional residual capacity decreased and extravascular lung water increased similarly in these three categories. Lung weight, wet-to-dry ratio, and histologic scores were similar, regardless of ventilatory strategies and power levels. However, the alveolar edema score was higher in the low power groups. High PEEP had the greatest impact on hemodynamics, leading to increased need for fluids. Adverse events (early mortality and pneumothorax) also occurred more frequently in the high PEEP groups. CONCLUSIONS: Different ventilatory strategies, delivered at iso-power, led to similar anatomical lung injury. The different systemic consequences of high PEEP underline that ventilator-induced lung injury must be evaluated in the context of the whole body.

Nonantibiotic Pharmacological Treatment of Severe Chronic Obstructive Pulmonary Disease Exacerbations.

Severe, acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a rapid deterioration of the respiratory symptoms of patients with COPD, requiring hospital admission and escalation of pharmacological and nonpharmacological care including the more severe cases of respiratory failure and admission to an intensive care unit (ICU). These events severely impact patients' quality of life and prognosis. This review will describe the nonantibiotic, pharmacological treatment options available for critically ill patients with AECOPD. The aim of treatment is to alleviate symptoms, improve patient's functional and respiratory status, reduce mortality, reduce the risk or the duration of invasive mechanical ventilation, and prevent reexacerbations. Inhaled bronchodilators (i.e., short-acting ß2-agonists and anticholinergics) and systemic corticosteroids are the main drugs used in the treatment of AECOPD. These drugs are also used in the treatment of stable COPD and in the treatment of AECOPD patients in the non-ICU or community setting. Other drugs are essentially only used in the ICU setting such as inhaled anesthetic agents, ketamine, intravenous methylxanthines, and magnesium. Finally, recently developed drugs, such as the specific phosphodiesterase-4 inhibitors, may play a role in the prevention of relapsing AECOPD following a critical event than the treatment of the exacerbation itself. Although they significantly improve the survival of critically ill patients with AECOPD, none of available drugs, alone or combined, is able to significantly modify the prognosis of patients with COPD. This remains an open challenge for the current and future generations of researchers and clinicians.

Understanding Lactatemia in Human Sepsis. Potential Impact for Early Management.

Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy.Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactate, and base excess to better determine the origin of lactate.Methods: This was a post hoc analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of ScvO2. We defined the "alactic base excess," as the sum of lactate and standard base excess.Measurements and Main Results: Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. ScvO2 was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of ScvO2. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance.Conclusions: Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.

Prediction of readiness to decannulation from venovenous extracorporeal membrane oxygenation.

OBJECTIVE: The criteria and process for liberation from extracorporeal membrane oxygenation in patients with severe acute respiratory distress syndrome are not standardized. The predictive accuracy of the oxygen challenge test as a diagnostic test in determining weaning and decannulation from venovenous extracorporeal membrane oxygenation was tested. DESIGN: A single-centre, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure centre in a university hospital in the United Kingdom. PATIENTS: 253 adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients had median age: 43 years (interquartile range: 32-52) years, extracorporeal membrane oxygenation days: 9 (interquartile range: 6-14) and acute physiology and chronic health evaluation II score 17.5 (interquartile range: 15-20). Oxygen challenge test value (PaO2-OCT) with best prediction was 31 kPa (232 mmHg; sensitivity 0.74; specificity 0.70; area under curve 0.77 (confidence interval: 0.73-0.81)). PaO2-OCT did not perform well as a prospective test to identify readiness to decannulation. Only 24 patients (10%) were decannulated 48 hours after their first positive oxygen challenge test (true positive) and 73.4% patients were false positives (positive oxygen challenge test but not decannulated). True positives had higher tidal volume (541 ± 218 vs 368 mL ± 210; p < 0.05) and minute ventilation (9.34 ± 5.36 vs 6.33 L/min ± 4.43; p < 0.05). Blood flow (3.17 ± 0.23 vs 3.53 L/min ± 0.56; p < 0.05), sweep gas flow (1.42 ±1.83 vs 3.74 L/min ± 2.43; p < 0.05) and extracorporeal membrane oxygenation minute volume at time of first positive oxygen challenge test was lower in true positives (1.66 ± 2.26 vs 4.82 ± 3.43 L/min). This was a strong predictor for decannulation within 48 hours (area under curve: 0.88, confidence interval: 0.88-0.89). CONCLUSIONS: In severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation, the PaO2-OCT is a poor predictor of readiness to decannulate from extracorporeal membrane oxygenation. Additional factors involved in the control of respiratory drive and carbon dioxide clearance, particularly native lung dead space and total minute ventilation, should be assessed.

Extracorporeal CO2 Removal: The Minimally Invasive Approach, Theory, and Practice.

OBJECTIVES: Minimally invasive extracorporeal CO2 removal is an accepted supportive treatment in chronic obstructive pulmonary disease patients. Conversely, the potential of such technique in treating acute respiratory distress syndrome patients remains to be investigated. The aim of this study was: 1) to quantify membrane lung CO2 removal (VCO2ML) under different conditions and 2) to quantify the natural lung CO2 removal (VCO2NL) and to what extent mechanical ventilation can be reduced while maintaining total expired CO2 (VCO2tot = VCO2ML + VCO2NL) and arterial PCO2 constant. DESIGN: Experimental animal study. SETTING: Department of Experimental Animal Medicine, University of Göttingen, Germany. SUBJECTS: Eight healthy pigs (57.7 ± 5 kg). INTERVENTIONS: The animals were sedated, ventilated, and connected to the artificial lung system (surface 1.8 m, polymethylpentene membrane, filling volume 125 mL) through a 13F catheter. VCO2ML was measured under different combinations of inflow PCO2 (38.9 ± 3.3, 65 ± 5.7, and 89.9 ± 12.9 mm Hg), extracorporeal blood flow (100, 200, 300, and 400 mL/min), and gas flow (4, 6, and 12 L/min). At each setting, we measured VCO2ML, VCO2NL, lung mechanics, and blood gases. MEASUREMENTS AND MAIN RESULTS: VCO2ML increased linearly with extracorporeal blood flow and inflow PCO2 but was not affected by gas flow. The outflow PCO2 was similar regardless of inflow PCO2 and extracorporeal blood flow, suggesting that VCO2ML was maximally exploited in each experimental condition. Mechanical ventilation could be reduced by up to 80-90% while maintaining a constant PaCO2. CONCLUSIONS: Minimally invasive extracorporeal CO2 removal removes a relevant amount of CO2 thus allowing mechanical ventilation to be significantly reduced depending on extracorporeal blood flow and inflow PCO2. Extracorporeal CO2 removal may provide the physiologic prerequisites for controlling ventilator-induced lung injury.

Lung Recruitability in Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Quantification of potential for lung recruitment may guide the ventilatory strategy in acute respiratory distress syndrome. However, there are no quantitative data on recruitability in patients with severe acute respiratory distress syndrome who require extracorporeal membrane oxygenation. We sought to quantify potential for lung recruitment and its relationship with outcomes in this cohort of patients. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center in a university hospital in the United Kingdom. PATIENTS: Forty-seven adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe acute respiratory distress syndrome-mainly of pulmonary origin (86%)-the potential for lung recruitment and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue were assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were categorized as high or low potential for lung recruitment based on the median potential for lung recruitment value of the study population. The median potential for lung recruitment was 24.3% (interquartile range = 11.4-37%) ranging from -2% to 76.3% of the total lung weight. Patients with potential for lung recruitment above the median had significantly shorter extracorporeal membrane oxygenation duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), but mortality was not statistically different (24% vs 46%; p = 0.159). CONCLUSIONS: We observed significant variability in potential for lung recruitment in patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Patients with high potential for lung recruitment had a shorter ICU stay and shorter extracorporeal membrane oxygenation duration.

Positive End-expiratory Pressure and Mechanical Power.

BACKGROUND: Positive end-expiratory pressure is usually considered protective against ventilation-induced lung injury by reducing atelectrauma and improving lung homogeneity. However, positive end-expiratory pressure, together with tidal volume, gas flow, and respiratory rate, contributes to the mechanical power required to ventilate the lung. This study aimed at investigating the effects of increasing mechanical power by selectively modifying its positive end-expiratory pressure component. METHODS: Thirty-six healthy piglets (23.3 ± 2.3 kg) were ventilated prone for 50 h at 30 breaths/min and with a tidal volume equal to functional residual capacity. Positive end-expiratory pressure levels (0, 4, 7, 11, 14, and 18 cm H2O) were applied to six groups of six animals. Respiratory, gas exchange, and hemodynamic variables were recorded every 6 h. Lung weight and wet-to-dry ratio were measured, and histologic samples were collected. RESULTS: Lung mechanical power was similar at 0 (8.8 ± 3.8 J/min), 4 (8.9 ± 4.4 J/min), and 7 (9.6 ± 4.3 J/min) cm H2O positive end-expiratory pressure, and it linearly increased thereafter from 15.5 ± 3.6 J/min (positive end-expiratory pressure, 11 cm H2O) to 18.7 ± 6 J/min (positive end-expiratory pressure, 14 cm H2O) and 22 ± 6.1 J/min (positive end-expiratory pressure, 18 cm H2O). Lung elastances, vascular congestion, atelectasis, inflammation, and septal rupture decreased from zero end-expiratory pressure to 4 to 7 cm H2O (P < 0.0001) and increased progressively at higher positive end-expiratory pressure. At these higher positive end-expiratory pressure levels, striking hemodynamic impairment and death manifested (mortality 0% at positive end-expiratory pressure 0 to 11 cm H2O, 33% at 14 cm H2O, and 50% at 18 cm H2O positive end-expiratory pressure). From zero end-expiratory pressure to 18 cm H2O, mean pulmonary arterial pressure (from 19.7 ± 5.3 to 32.2 ± 9.2 mmHg), fluid administration (from 537 ± 403 to 2043 ± 930 ml), and noradrenaline infusion (0.04 ± 0.09 to 0.34 ± 0.31 µg · kg(-1) · min(-1)) progressively increased (P < 0.0001). Lung weight and lung wet-to-dry ratios were not significantly different across the groups. The lung mechanical power level that best discriminated between more versus less severe damage was 13 ± 1 J/min. CONCLUSIONS: Less than 7 cm H2O positive end-expiratory pressure reduced atelectrauma encountered at zero end-expiratory pressure. Above a defined power threshold, sustained positive end-expiratory pressure contributed to potentially lethal lung damage and hemodynamic impairment.

Reclassifying Acute Respiratory Distress Syndrome.

RATIONALE: The ratio of PaO2 to FiO2 (P/F) defines acute respiratory distress syndrome (ARDS) severity and suggests appropriate therapies. OBJECTIVES: We investigated 1) whether a 150-mm-Hg P/F threshold within the range of moderate ARDS (100-200 mm Hg) would define two subgroups that were more homogeneous; and 2) which criteria led the clinicians to apply extracorporeal membrane oxygenation (ECMO) in severe ARDS. METHODS: At the 150-mm-Hg P/F threshold, moderate patients were split into mild-moderate (n = 50) and moderate-severe (n = 55) groups. Patients with severe ARDS (FiO2 not available in three patients) were split into higher (n = 63) and lower (n = 18) FiO2 groups at an 80% FiO2 threshold. MEASUREMENTS AND MAIN RESULTS: Compared with mild-moderate ARDS, patients with moderate-severe ARDS had higher peak pressures, PaCO2, and pH. They also had heavier lungs, greater inhomogeneity, more noninflated tissue, and greater lung recruitability. Within 84 patients with severe ARDS (P/F < 100 mm Hg), 75% belonged to the higher FiO2 subgroup. They differed from the patients with severe ARDS with lower FiO2 only in PaCO2 and lung weight. Forty-one of 46 patients treated with ECMO belonged to the higher FiO2 group. Within this group, the patients receiving ECMO had higher PaCO2 than the 22 non-ECMO patients. The inhomogeneity ratio, total lung weight, and noninflated tissue were also significantly higher. CONCLUSIONS: Using the 150-mm-Hg P/F threshold gave a more homogeneous distribution of patients with ARDS across the severity subgroups and identified two populations that differed in their anatomical and physiological characteristics. The patients treated with ECMO belonged to the severe ARDS group, and almost 90% of them belonged to the higher FiO2 subgroup.

Septic shock-3 vs 2: an analysis of the ALBIOS study.

BACKGROUND: A reanalysis of the ALBIOS trial suggested that patients with septic shock - defined by vasopressor-dependent hypotension in the presence of severe sepsis (Shock-2) - had a survival benefit when treated with albumin. The new septic shock definition (Shock-3) added the criterion of a lactate threshold of 2 mmol/L. We investigated how the populations defined according to Shock-2 and Shock-3 differed and whether the albumin benefit would be confirmed. METHODS: This is a retrospective analysis of the ALBIOS study, a randomized controlled study conducted between 2008 and 2012 in 100 intensive care units in Italy comparing the administration of 20% albumin and crystalloids versus crystalloids alone in patients with severe sepsis or septic shock. We analyzed data from 1741 patients from ALBIOS with serum lactate measurement available at baseline. We compared group size, physiological variables and 90-day mortality between patients defined by Shock-2 and Shock-3 and between the albumin and crystalloid treatment groups. RESULTS: We compared the Shock-2 and the Shock-3 definitions and the albumin and crystalloid treatment groups in terms of group size and physiological, laboratory and outcome variables. The Shock-3 definition reduced the population with shock by 34%. The Shock-3 group had higher lactate (p < 0.001), greater resuscitation-fluid requirement (p = 0.014), higher Simplified Acute Physiology Score II (p < 0.001) and Sepsis-related Organ Failure Assessment scores (p = 0.022), lower platelet count (p = 0.002) and higher 90-day mortality (46.7% vs 51.9%; p = 0.031). Albumin decreased mortality in Shock-2 patients compared to crystalloids (43.5% vs 49.9%; 12.6% relative risk reduction; p = 0.04). In patients defined by Shock-3 a similar benefit was observed for albumin with a 11.3% relative risk reduction (48.7% vs 54.9%; 11.3% relative risk reduction; p = 0.22). CONCLUSIONS: The Sepsis-3 definition reduced the size of the population with shock and showed a similar effect size in the benefits of albumin. The Shock-3 criteria will markedly slow patients' recruitment rates, in view of testing albumin in septic shock. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00707122 . Registered on 30 June 2008.

Meta-analysis of the Sources of Bleeding after Adult Cardiac Surgery.

OBJECTIVE: The aim of this study was to pool data on the proportion and prognostic impact of sources of bleeding in patients requiring re-exploration after adult cardiac surgery. DESIGN: Systematic review of the literature and meta-analysis. SETTING: Multistitutional study. MEASUREMENTS AND MAIN RESULTS: A literature review was performed to identify studies published since 1990 evaluating the outcome after reoperation for bleeding or tamponade after adult cardiac surgery. Eighteen studies including 5,1497 patients fulfilled the selection criteria. Reoperation for bleeding/tamponade was performed in 2,455 patients (4.6%; 95% confidence interval [CI] 3.9%-5.2%, I2 92%). These had a significantly higher risk of in-hospital/30-day mortality compared with patients not reoperated for bleeding (pooled rates: 9.3% v 2.3%; risk ratio 3.30; 95% CI 2.52-4.32; I2 47%; 8 studies; 25,463 patients). Surgical sites of bleeding were identified in 65.7% of cases (95% CI 58.3%-73.2%; I2 94%), cardiac site bleeding in 40.9% of cases (95% CI 29.7%-52.0%; I2 94%), and mediastinal/sternum site bleeding in 27.0% of cases (95% CI 16.8%-37.3%; I2 94%). The main sites of bleeding were the body of the graft (20.2%), the sternum (17.0%), vascular sutures (12.5%), the internal mammary artery harvest site (13.0%), and anastomoses (9.9%). In metaregression, surgical site bleeding was associated with a lower risk of in-hospital/30-day mortality compared with diffuse bleeding (p = 0.003). CONCLUSIONS: Surgical site bleeding is identified in two-thirds of patients undergoing re-exploration after adult cardiac surgery. Meticulous surgical technique and systematic intraoperative checking of potential surgical sites of bleeding at the time of the original cardiac surgery may reduce the risk of such a severe complication.

The future of mechanical ventilation: lessons from the present and the past.

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.

Thromboelastometry guided fibrinogen replacement therapy in cardiac surgery: a retrospective observational study.

This retrospective, observational study compared the impact of a point-of-care rotational thromboelastometry (ROTEM®) method versus conventional bleeding management in terms of postoperative (24-h) blood loss, intraoperative and postoperative (24-h) transfusion requirement and length of stay in the postoperative intensive care unit (ICU) in patients undergoing cardiac surgery. Forty consecutive patients undergoing cardiac surgery under ROTEM®-guided hemostatic management were enrolled; the control population included 40 selected patients undergoing similar interventions without ROTEM® monitoring. Significantly more patients in the thromboelastometry group versus the control group received fibrinogen (45 vs 10 %; p < 0.0001), while fewer received a transfusion (40 vs 72.5 %; p < 0.0033). Compared with control group patients, those in the thromboelastometry group had less postoperative bleeding (285 vs 393 mL; p < 0.0001), a shorter time from cardiopulmonary bypass discontinuation to skin suture (79.3 vs 92.6 min; p = 0.0043) and a shorter stay in the ICU (43.7 vs 52.5 h; p = 0.0002). In our preliminary experience, ROTEM®-guided bleeding management was superior to conventional management of bleeding in patients undergoing complex cardiac surgery with cardiopulmonary bypass in terms of reduced postoperative blood loss, transfusion requirement, and length of ICU stay.

Outcome of Jehovah's Witnesses after adult cardiac surgery: systematic review and meta-analysis of comparative studies.

BACKGROUND: The objective was to evaluate the early outcome after adult cardiac surgery in Jehovah's Witnesses (JWs) compared with controls not refusing blood transfusions. STUDY DESIGN AND METHODS: A literature review was performed through PubMed, Scopus, and Google Scholar to identify any comparative study evaluating the outcome of JWs and patients not refusing blood transfusion after adult cardiac surgery. RESULTS: Six studies comparing the outcome of 564 JWs and 903 controls fulfilled the inclusion criteria of this study. All series included a matched control cohort. Baseline characteristics of these two cohorts were similar, but JWs had higher hemoglobin (Hb) levels as reported in three studies. Pooled analysis of postoperative outcomes showed that JWs had higher postoperative levels of Hb (data from four studies: mean, 11.5 g/L vs. 9.8 g/L; p < 0.001) and significantly less postoperative blood loss (mean, 402 mL vs. 826 mL; p < 0.001) compared to controls. JWs and controls had similar early outcome. However, JWs had a nonsignificant trend toward decreased early mortality (2.6% vs. 3.6%; p = 0.318), reoperation for bleeding (3.2% vs. 4.7%; p = 0.070), atrial fibrillation (9.9% vs. 14.3%; p = 0.056), stroke (2.2% vs. 3.1%; p = 0.439), myocardial infarction (0.4% vs. 1.4%; p = 0.203), and length of stay in the intensive care unit (1.5 days vs. 2.0 days; p = 0.081). CONCLUSION: JWs undergoing adult cardiac surgery have a nonsignificant trend toward better early outcome than controls receiving or not blood transfusions. The suboptimal quality of available studies prevents conclusive results on the possible benefits of a transfusion-free strategy in patients not refusing blood transfusion.

Basic data from 176 studies on the immediate outcome after aortic valve replacement with or without coronary artery bypass surgery.

OBJECTIVE: The aim of this study was to summarize the immediate outcome after aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG). DESIGN: Systematic review and meta-analysis. SETTING: University hospitals. PARTICIPANTS: Participants were 683,286 patients who underwent AVR with or without CABG. Patients undergoing other major cardiac procedures were excluded from this analysis. INTERVENTIONS: AVR with or without CABG. MEASUREMENTS AND MAIN RESULTS: Operative mortality after AVR with or without concomitant CABG was 4.3%, stroke 2.1%, pacemaker implantation 5.9%, and dialysis 2.2%. After isolated AVR, operative mortality was 3.3%, stroke 1.7%, pacemaker implantation 3.3%, and dialysis 1.6%. Mortality was increased among very elderly (< 60 years: 3.3%, 60-69 years: 2.7%, 70-79 years: 3.8%,≥ 80 years: 6.1%, p < 0.001). Prevalence of minimally invasive AVR (mini-AVR) was associated with significantly lower operative mortality (p = 0.039, 46 studies). Mini-AVR only tended toward lower mortality when included in meta-regression analysis as a dichotomous variable (mini-AVR 4,367 patients: 2.3%, 95% CI 1.8-2.9% v full sternotomy 11,076 patients: 3.5%, 95% CI 28-4.1%, p = 0.088). Operative mortality after AVR plus CABG was 5.5% (versus isolated AVR: p < 0.001), stroke 3.0%, pacemaker implantation 3.9%, and dialysis 5.6%. Mortality was high in all age strata, particularly among very elderly (mean age < 70 years: 4.8%, mean age 70-79 years: 4.7%; mean age ≥ 80 years: 8.4%, p = 0.002). CONCLUSIONS: Isolated AVR is associated with low mortality and morbidity. Coronary artery disease requiring concomitant CABG increases the operative mortality. Patients requiring AVR and CABG should be the main target of less-invasive treatment strategies.