Luciano Gattinoni

• Doctor of Medicine
• Professor at Universitätsmedizin Göttingen

Measurement of CO during VV-ECMO

Assessing and quantifying recruitability are important for characterizing ARDS severity and for reducing or preventing the atelectrauma caused by the cyclic opening and closing of pulmonary units. Over the years, several methods for recruitment assessment have been developed, grouped into three main approaches: 1) Quantitative CT Scanning: This met...

The selection and intensity of respiratory support for ARDS are guided by PaO2/FiO2. However, ventilator-induced lung injury (VILI) is linked to respiratory mechanics and ventilator settings. We explored whether the VILI risk is related to ARDS severity based on oxygenation. We analysed data on 228 ARDS subjects with PaO2/FiO2 < 200 mmHg, categoriz...

Background Ventilator-induced lung injury (VILI) is one of the side effects of mechanical ventilation during ARDS; a prerequisite for averting it is the quantification of its risk factors associated with a given ventilatory setting. Many clinical variables have been proposed as predictors of VILI, of which driving pressure is the most widely used....

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a supportive therapy for acute respiratory failure with increased risk of packed red blood cells (PRBC) transfusion. Blood cell salvage (BCS) aims to reduce blood transfusion, but its efficacy is unclear. This study aimed to estimate the effect of BCS at the time of removal of...

Rationale: The pathophysiological relationship between fluid administration, fluid balance, and mechanical ventilation in the development of lung injury is unclear. Objectives: To quantify the relative contribution of mechanical power and fluid balance in the development of lung injury. Methods: Thirty-nine healthy female pigs, divided into four...

Objectives: The intensity of respiratory treatment in acute respiratory distress syndrome (ARDS) is traditionally adjusted based on oxygenation severity, as defined by the mild, moderate, and severe Berlin classifications. However, ventilator-induced lung injury (VILI) is primarily determined by ventilator settings, namely tidal volume, respiratory...

Kidney response to acute and mechanically induced variation in ventilation associated with different levels of PEEP has not been investigated. We aimed to quantify the effect of ventilatory settings on renal acid–base compensation. Forty‐one pigs undergoing hypo‐ (<0.2 Lkg⁻¹ min⁻¹, PEEP 25 cmH2O), intermediate (0.2–0.4 Lkg⁻¹ min⁻¹ with either PEEP...

Persistent shortcomings of invasive positive pressure ventilation make it less than an ideal intervention. Over the course of more than seven decades, clinical experience and scientific investigation have helped define its range of hazards and limitations. Apart from compromised airway clearance and lower airway contamination imposed by endotrachea...

Rationale Mechanical power (MP) is a summary variable incorporating all causes of ventilator-induced-lung-injury (VILI). We expressed MP as the ratio between observed and normal expected values (MP ratio ). Objective To define a threshold value of MP ratio leading to the development of VILI. Methods In a population of 82 healthy pigs, a threshold...

BACKGROUND: Lung edema and baby lung size are considered markers of ventilator-induced lung injury. We investigated at what extent mechanical power (MP) and fluid balance (FB) may contribute to it. MATERIALS AND METHODS: Forty pigs were divided in four groups. Group 1: treated (48hours) with high MP (14,5 J/min) and high FB (+4l), Group 2: high MP,...

Background: The ratio of SaO2/FiO2 has been recently proposed as a surrogate of PaO2/FiO2 in the finding of ARDS severity. In this study, we investigated the relationship between these two variables in theory and practice. Methods: Effect of pH: Theory: We compute, at a given SpO2/FiO2 ranging from 50 to 350, what was the FiO2 fraction which gene...

Background Mechanical power (MP) is a summary variable that includes all the factors associated with ventilator-induced lung injury (VILI). Being the MP an extensive property of the system, its normalization is needed. In analogy with ventilatory ratio, a MPratio may be used. Objective To determine whether there is a MPratio threshold associated wi...

Background: Mechanical ventilation may cause Ventilator-Induced-Lung-Injury (VILI) during ARDS. Therefore, it is important to identify possible indicators of VILI risk. In this experimental study, we compared the effectiveness of Driving Pressure (DP) and Mechanical Power Ratio (MPR) in predicting lung damage. Methods: The study population consist...

BACKGROUND: Septic shock is a paradigm of energy crisis due to increased oxygen extraction up to a critical oxygen delivery, beyond which the organism increases anaerobic energy production with consecutive lactate increase, serious acid-base imbalance and multi-organ failure. Current treatment consists of correcting "energy delivery" with cardiocir...

Background The individual components of mechanical ventilation may have distinct effects on kidney perfusion and on the risk of developing acute kidney injury; we aimed to explore ventilatory predictors of acute kidney failure and the hemodynamic changes consequent to experimental high-power mechanical ventilation. Methods Secondary analysis of tw...

It is commonly assumed that changes in plasma strong ion difference (SID) result in equal changes in whole-blood base excess (BE). However, at varying pH, albumin ionic-binding and transerythrocyte shifts alter the SID of plasma without affecting that of whole-blood (SID wb), i.e., the BE. We hypothesize that, during acidosis, 1) an expected plasma...

Introduction The use of the pulmonary artery catheter has decreased overtime; central venous blood gases are generally used in place of mixed venous samples. We want to evaluate the accuracy of oxygen and carbon dioxide related parameters from a central versus a mixed venous sample, and whether this difference is influenced by mechanical ventilatio...

Introduction Lung weight is an important study endpoint to assess lung edema in porcine experiments on acute respiratory distress syndrome and ventilatory induced lung injury. Evidence on the relationship between lung–body weight relationship is lacking in the literature. The aim of this work is to provide a reference equation between normal lung a...

Background: Despite the fervent scientific effort, a state-of-the art assessment of the different causes of hypoxemia (shunt, ventilation-perfusion mismatch and diffusion limitation) in COVID-19 ARDS is currently lacking. In this study we aimed to understand what is the relative contribution of the different mechanisms of hypoxemia in this disease...

Control of Breathing Using an Extracorporeal Membrane Lung. By T Kolobow, L Gattinoni, TA Tomlinson, JE Pierce. Anesthesiology 1977; 46:138–41. Reprinted with permission. Body Position Changes Redistribute Lung Computed-Tomographic Density in Patients with Acute Respiratory Failure. By L Gattinoni, P Pelosi, G Vitale, A Pesenti, L D’Andrea, D Masch...

The conditions of temperature, pressure and saturation in which respiratory gas volumes are expressed (STPD, ATPS or BTPS) are physiologically relevant, but often ignored or unknown in clinical practice. In this study we aimed to investigate whether and at which extent the gas volumes corrections, either in natural and artificial lung, may alter ke...

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to cor...

Background: Despite its diagnostic and prognostic importance, physiologic dead space fraction is not included in the current ARDS definition or severity classification. ARDS caused by COVID-19 (C-ARDS) is characterized by increased physiologic dead space fraction and hypoxemia. Our aim was to investigate the relationship between dead space indices...

At the bedside, assessing the risk of ventilator-induced lung injury (VILI) requires parameters readily measured by the clinician. For this purpose, driving pressure (DP) and end-inspiratory static ‘plateau’ pressure (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbs...

COVID-19 pandemic has seen an unprecedented number of patients presenting with acute respiratory distress syndrome to the intensive care units all over the world. Between August and November 2022, we performed research on PubMed screening all publications on COVID-19 disease and respiratory failure and its treatment. In this review we focused on CO...

Historical background The prone position was first proposed on theoretical background in 1974 (more advantageous distribution of mechanical ventilation). The first clinical report on 5 ARDS patients in 1976 showed remarkable improvement of oxygenation after pronation. Pathophysiology The findings in CT scans enhanced the use of prone position in...

Rationale: In the ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial, oxygenation was similar between intervention and conventional groups, while minute ventilation was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO2 removal (ECCO2R), provided that o...

On the 50th anniversary of the Society of Critical Care Medicine's journal Critical Care Medicine, critical care pioneers reflect on the importance of the journal to their careers and to the development of the field of adult and pediatric critical care.

Background Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with higher risk of respiratory failure, we assessed lung mechanics in non-intubated patients with COVID-19 pneumonia aimed at: 1) describe their characteristics; 2) compare lung mechanics between patients who received respiratory treatme...

Background Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing...

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as deadspace and shunt in 13 anesthetized swine undergoing centrally canulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of c...

Background Ventilatory ratio (VR) has been proposed as an alternative approach to estimate physiological dead space. However, the absolute value of VR, at constant dead space, might be affected by venous admixture and CO2 volume expired per minute (VCO2). Methods This was a retrospective, observational study of mechanically ventilated patients wit...

Purpose To explore the feasibility of long-term application of ultraprotective ventilation with low flow ECCO2R support in moderate-severe ARDS patients and the reduction of mechanical power (MP) compared to lung protective ventilation. Material and methods ARDS patients with PaO2/FiO2 < 200, PEEP of 10 cmH2O, tidal volume 6 ml/Kg of predicted bod...

The amount of energy delivered to the respiratory system is recognized as a cause of Ventilator Induced Lung Injury (VILI). How energy dissipation within the lung causes damage is still a matter of debate. Expiratory flow control has been proposed as a strategy to reduce the energy dissipated into the respiratory system during expiration and, possi...

Objectives: Head-elevated body positioning, a default clinical practice, predictably increases end-expiratory transpulmonary pressure and aerated lung volume. In acute respiratory distress syndrome (ARDS), however, the net effect of such vertical inclination on tidal mechanics depends upon whether lung recruitment or overdistension predominates. W...

Background: Chest wall loading has been shown to paradoxically improve respiratory system compliance (CRS) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The most likely, albeit unconfirmed, mechanism is relief of end-tidal overdistension in 'baby lungs' of low-capacity. The purpose of this study was to define how...

Treatment of respiratory failure has improved dramatically since the polio epidemic in the 1950s with the use of invasive techniques for respiratory support: mechanical ventilation and extracorporeal respiratory support. However, respiratory support is only a supportive therapy, designed to "buy time" while the disease causing respiratory failure a...

Background Repeated expenditure of energy and its generation of damaging strain are required to injure the lung by ventilation (VILI). Mathematical modeling of passively inflated, single-compartment lungs with uniform parameters for resistance and compliance indicates that standard clinical modes (flow patterns) differ impressively with respect to...

Rationale: Weaning from veno-venous extracorporeal membrane oxygenation (VV-ECMO) is based on oxygenation and not on carbon dioxide elimination. Objective: To predict readiness to wean from VV-ECMO Methods: In this multicenter study of mechanically ventilated adults with severe acute respiratory distress syndrome (ARDS) receiving VV-ECMO, we inv...

The extent of ventilator-induced lung injury may be related to the intensity of mechanical ventilation--expressed as mechanical power. In the present study, we investigated whether there is a safe threshold, below which lung damage is absent. Three groups of six healthy pigs (29.5 ± 2.5 kg) were ventilated prone for 48 h at mechanical power of 3, 7...

Objectives: Lung damage during mechanical ventilation involves lung volume and alveolar water content, and lung ultrasound (LUS) and electrical impedance tomography changes are related to these variables. We investigated whether these techniques may detect any signal modification during the development of ventilator-induced lung injury (VILI). De...

The prone position has been used to improve oxygenation in patients affected by acute respiratory distress syndrome, but its role in patients with COVID-19 is still unclear when these patients are breathing spontaneously. Mechanisms of ventilation and perfusion in the prone position are discussed, with new insights on how these changes relate to pa...

Coronavirus disease 2019 (COVID-19) pneumonia is an evolving disease. We will focus on the development of its pathophysiologic characteristics over time, and how these time-related changes determine modifications in treatment. In the emergency department: the peculiar characteristic is the coexistence, in a significant fraction of patients, of seve...

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with su...

Purpose of review: More than 230 million people have tested positive for severe acute respiratory syndrome-coronavirus-2 infection globally by September 2021. The infection affects primarily the function of the respiratory system, where ∼20% of infected individuals develop coronavirus-19 disease (COVID-19) pneumonia. This review provides an update...

Background Septic shock is characterized by breakdown of the endothelial glycocalyx and endothelial damage, contributing to fluid extravasation, organ failure and death. Albumin has shown benefit in septic shock patients. Our aims were: (1) to identify the relations between circulating levels of syndecan-1 (SYN-1), sphingosine-1-phosphate (S1P) (en...

Background The physiological dead space is a strong indicator of severity and outcome of acute respiratory distress syndrome (ARDS). The “ideal” alveolar PCO 2 , in equilibrium with pulmonary capillary PCO 2 , is a central concept in the physiological dead space measurement. As it cannot be measured, it is surrogated by arterial PCO 2 which, unfort...

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can...

As exemplified by prone positioning, regional variations of lung and chest wall properties provide possibilities for modifying transpulmonary pressures and suggest that clinical interventions related to the judicious application of external pressure may yield benefit. Recent observations made in late-phase patients with severe ARDS caused by COVID-...

Background High rates of inflation energy delivery coupled with transpulmonary tidal pressures of sufficient magnitude may augment the risk of damage to vulnerable, stress-focused units within a mechanically heterogeneous lung. Apart from flow amplitude, the clinician-selected flow waveform , a relatively neglected dimension of inflation power, may...

PurposeThis study aimed at investigating the mechanisms underlying the oxygenation response to proning and recruitment maneuvers in coronavirus disease 2019 (COVID-19) pneumonia.Methods Twenty-five patients with COVID-19 pneumonia, at variable times since admission (from 1 to 3 weeks), underwent computed tomography (CT) lung scans, gas-exchange and...

PurposeWe investigated if the stress applied to the lung during non-invasive respiratory support may contribute to the coronavirus disease 2019 (COVID-19) progression.Methods Single-center, prospective, cohort study of 140 consecutive COVID-19 pneumonia patients treated in high-dependency unit with continuous positive airway pressure (n = 131) or n...

Knowledge of gas volume, tissue mass and recruitability measured by the quantitative CT scan analysis (CT-qa) is important when setting the mechanical ventilation in acute respiratory distress syndrome (ARDS). Yet, the manual segmentation of the lung requires a considerable workload. Our goal was to provide an automatic, clinically applicable and r...

Background: Ventilator-induced lung injury (VILI) via respiratory mechanics is deeply interwoven with hemodynamic, kidney and fluid/electrolyte changes. We aimed to assess the role of positive fluid balance in the framework of ventilation-induced lung injury. Methods: Post-hoc analysis of seventy-eight pigs invasively ventilated for 48 h with mecha...

Inflammation and oxidative stress characterize sepsis and determine its severity. In this study, we investigated the relationship between albumin oxidation and sepsis severity in a selected cohort of patients from the Albumin Italian Outcome Study (ALBIOS). A retrospective analysis was conducted on the oxidation forms of human albumin [human mercap...

Acute respiratory distress syndrome (ARDS) is an acute respiratory illness characterised by bilateral chest radiographical opacities with severe hypoxaemia due to non-cardiogenic pulmonary oedema. The COVID-19 pandemic has caused an increase in ARDS and highlighted challenges associated with this syndrome, including its unacceptably high mortality...

Background: High rates of inflation energy delivery coupled with transpulmonary tidal pressures of sufficient magnitude may augment the risk of damage to vulnerable, stress-focused units within a mechanically heterogeneous lung. Apart from flow amplitude, the clinician-selected flow waveform, a relatively neglected dimension of inflation power, may...

Rationale: Septic patients have typically reduced concentrations of hemoglobin and albumin, the major components of non-carbonic buffer power(β). This could expose patients to high pH variations during acid-base disorders. Objectives: To compare, in-vitro, non-carbonic β of septic patients with that of healthy volunteers, and evaluate its distinct...

Background To determine the frequency of, and factors associated with, death in hospital following ICU discharge to the ward. Methods The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conduc...

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 2...

Background: In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission. Methods: In this retrospective observational cohort study we enrolled a study population...

Respiratory failure (RF) is defined as the acute or chronic impairment of respiratory system function to maintain normal oxygen and CO2 values when breathing room air. ‘Oxygenation failure’ occurs when O2 partial pressure (PaO2) value is lower than the normal predicted values for age and altitude and may be due to ventilation/perfusion mismatch or...

Cardiovascular diseases (CVDs) are a major cause of premature death worldwide and a cause of loss of disability-adjusted life years. For most types of CVD early diagnosis and intervention are independent drivers of patient outcome. Clinicians must be properly trained and centres appropriately equipped in order to deal with these critically ill card...

COVID-19 infection may lead to an Acute Respiratory Distress Syndrome where severe gas exchange derangements may be associated, at least in the early stages, only with minor pulmonary infiltrates. This suggests that the shunt associated to the gasless lung parenchyma is not sufficient to explain CARDS hypoxemia. We designed an algorithm (Vent ri Q...

Background The current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in intensive care unit are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). Methods An international, multicentre, prospective cohort study of patients presenting w...