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      Hypothermic total liquid ventilation after experimental aspiration-associated acute respiratory distress syndrome

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          Ultrafast cooling by total liquid ventilation (TLV) provides potent cardio- and neuroprotection after experimental cardiac arrest. However, this was evaluated in animals with no initial lung injury, whereas out-of-hospital cardiac arrest is frequently associated with early-onset pneumonia, which may lead to acute respiratory distress syndrome (ARDS). Here, our objective was to determine whether hypothermic TLV could be safe or even beneficial in an aspiration-associated ARDS animal model.


          ARDS was induced in anesthetized rabbits through a two-hits model including the intra-tracheal administration of a pH = 1 solution mimicking gastric content and subsequent gaseous non-protective ventilation during 90 min (tidal volume [Vt] = 10 ml/kg with positive end-expiration pressure [PEEP] = 0 cmH 2O). After this initial period, animals either received lung protective gas ventilation (LPV; Vt = 8 ml/kg and PEEP = 5 cmH 2O) under normothermic conditions, or hypothermic TLV (TLV; Vt = 8 ml/kg and end-expiratory volume = 15 ml/kg). Both strategies were applied for 120 min with a continuous monitoring of respiratory and cardiovascular parameters. Animals were then euthanized for pulmonary histological analyses.


          Eight rabbits were included in each group. Before randomization, all animals elicited ARDS with arterial oxygen partial pressure over inhaled oxygen fraction ratios (PaO 2/FiO 2) below 100 mmHg, as well as decreased lung compliance. After randomization, body temperature rapidly decreased in TLV versus LPV group (32.6 ± 0.6 vs. 38.2 ± 0.4 °C after 15 min). Static lung compliance and gas exchanges were not significantly different in the TLV versus LPV group (PaO 2/FiO 2 = 62 ± 4 vs. 52 ± 8 mmHg at the end of the procedure, respectively). Mean arterial pressure and arterial bicarbonates levels were significantly higher in TLV versus LPV. Histological analysis also showed significantly lower inflammation in TLV versus LPV group (median histological score = 3 vs. 4.5/5, respectively; p = 0.03).


          Hypothermic TLV can be safely induced in rabbits during aspiration-associated ARDS. It modified neither gas exchanges nor respiratory mechanics but reduced lung inflammation and hemodynamic failure in comparison with LPV. Since hypothermic TLV was previously shown to provide neuro- and cardio protective effects after cardiac arrest, these findings suggest a possible use of TLV in the settings of cardiac arrest-associated ARDS.

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          Most cited references 28

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          Evolution of mortality over time in patients receiving mechanical ventilation.

          Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. To estimate whether mortality in mechanically ventilated patients has changed over time. Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).
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            Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis.

            Although frequent, little is known about early-onset pneumonia that occurs in the postresuscitation period. Although induced hypothermia is recommended as a method of improving neurological outcome, its influence on the occurrence of early-onset pneumonia is not well defined. To describe the incidence, risk factors, causative agents, and impact on outcome of early-onset pneumonia occurring within 3 days after out-of-hospital cardiac arrest (OHCA). Retrospective analysis of a large cohort study of all patients successfully resuscitated after OHCA and admitted from July 2002 to March 2008 in two medical intensive care units (ICUs). Patients who presented accidental hypothermia or a known pneumonia before OHCA, or patients who died within the first 24 hours, were excluded. During this 6-year period, 845 patients were admitted after OHCA, and 641 consecutive patients were included. A total of 500 patients (78%) were treated with therapeutic hypothermia. In the first 3 days, 419 (65%) presented early-onset pneumonia. Multivariate analysis disclosed therapeutic hypothermia as the single independent risk factor of early-onset pneumonia (odds ratio, 1.90; 95% confidence interval, 1.28-2.80; P = 0.001). Early-onset pneumonia increased length of mechanical ventilation (5.7 ± 5.9 vs. 4.7 ± 6.2 d; P = 0.001) and ICU stay (7.9 ± 7.2 versus 6.7 ± 7.6 d; P = 0.001), but did not influence incidence of ventilator-associated pneumonia (P = 0.25), favorable neurologic outcome (P = 0.35), or ICU mortality (P = 0.26). After OHCA, therapeutic hypothermia is associated with an increased risk of early-onset pneumonia. This complication was associated with prolonged respiratory support and ICU stay, but did not significantly influence ICU mortality.
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              Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era.

              Infectious complications are frequently reported in critically ill patients, especially after cardiac arrest. Recent and widespread use of therapeutic hypothermia has raised concerns about increased septic complications, but no specific reappraisal has been performed. We investigated the infectious complications in cardiac arrest survivors and assessed their impact on morbidity and long-term outcome. Retrospective review of a prospectively acquired intensive care unit database. A 24-bed medical intensive care unit in a French university hospital. Between March 2004 and March 2008, consecutive patients admitted for management of resuscitated out-of-hospital cardiac arrest were considered. Patients dying within 24 hrs were excluded. All patients' files were reviewed to assess the development of infection. None. Of the 537 patients admitted after cardiac arrest, 421 were included and 281 patients (67%) presented 373 infectious complications. Pneumonia was the most frequent (318 episodes), followed by bloodstream infections (35 episodes) and catheter-related infections (11 episodes). When grouped together, Gram-negative bacteria were the most frequently isolated infectious germs (64%), but the main pathogen detected was Staphylococcus aureus (57 occurrences). Both application itself (83 vs. 73%; p = .02) and duration (1244 vs. 1176 mins; p = .05) of therapeutic hypothermia were significantly more frequent in infected patients. Infection was associated with increased mechanical ventilation duration (6 [2-9] vs. 3 [2-5.5] days; p < .001) and intensive care unit length of stay (7 [4-10] vs. 3 [2-7] days; p < .001). Nonetheless, there was no impact on intensive care unit mortality (174 [62%] vs. 92 [66%] patients; p = .45) or on favorable neurologic outcome (cerebral performance category 1-2, 102 [36%] vs. 47 [34%] patients; p = .58). Infectious complications are frequent after cardiac arrest and may be even more frequent after therapeutic hypothermia. Despite increase in care costs, long-term and clinically relevant outcomes do not seem to be impaired. This should not discourage the use of therapeutic hypothermia in cardiac arrest survivors.

                Author and article information

                +33 1 43 96 73 02 , renaud.tissier@vet-alfort.fr
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2 May 2018
                2 May 2018
                : 8
                [1 ]ISNI 0000 0001 2149 7878, GRID grid.410511.0, U955 – IMRB, Inserm, , UPEC, Ecole Nationale Vétérinaire d’Alfort, ; 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France
                [2 ]ISNI 0000 0001 2175 4109, GRID grid.50550.35, Paediatric and Neonatal Intensive Care Unit, Armand-Trousseau Hospital, UPMC, , APHP, ; Paris, France
                [3 ]ISNI 0000 0000 9064 6198, GRID grid.86715.3d, Université de Sherbrooke, ; Sherbrooke, QC Canada
                [4 ]ISNI 0000 0001 2175 4109, GRID grid.50550.35, Service d’Anesthésie et des Réanimations Chirurgicales, DHU A-TVB, Hôpitaux Universitaires Henri Mondor, , Assistance Publique des Hôpitaux de Paris, ; Créteil, France
                [5 ]ISNI 0000 0001 2175 4109, GRID grid.50550.35, UMR 1137, Inserm, Université Paris Diderot, Hôpital Louis Mourier, Réanimation Médico-chirurgicale, , APHP, ; Colombes, France
                [6 ]GRID grid.414093.b, UMR 970, Inserm, Paris Cardiovascular Research Center, , Hôpital Européen Georges Pompidou, ; Paris, France
                © The Author(s) 2018

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