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RATIONALE: Apart from hypoxic hepatitis (HH), the hepatic consequences of out-of-hospital cardiac arrest (OHCA) have been little studied. This cohort study aimed to investigate the characteristics of liver dysfunction resulting from OHCA and its association with outcomes. METHODS: Among the conventional static liver function tests used to define acute liver failure (ALF), we determined which one correlated more closely with the reference indocyanine green (ICG) clearance test in a series of OHCA patients from the CYRUS trial (NCT01595958). Subsequently, we assessed whether ALF, in addition to HH (i.e., acute liver injury), was an independent risk factor for death in a large cohort of OHCA patients admitted to two intensive care units between 2007 and 2017. RESULTS: ICG clearance, available for 22 patients, was impaired in 17 (77.3%) cases. Prothrombin time (PT) ratio was the only static liver function test that correlated significantly (r = -0.66, p < 0.01) with ICG clearance and was therefore used to define ALF, with the usual cutoff of < 50%. Of the 418 patients included in the analysis (sex ratio: 1.4; median age: 64 [53-75] years; non-shockable rhythm: 73%), 67 (16.0%) presented with ALF, and 61 (14.6%) had HH at admission. On day 28, 337 (80.6%) patients died. Following multivariate analysis, ALF at admission, OHCA occurring at home, absence of bystander, non-cardiac cause of OHCA, low-flow duration ≥ 20 min, and SOFA score excluding liver subscore at admission were independently associated with day 28 mortality. CONCLUSIONS: ALF occurred frequently after OHCA and, unlike HH, was independently associated with day 28 mortality.
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Reanimación Cardiopulmonar , Hepatitis , Fallo Hepático Agudo , Paro Cardíaco Extrahospitalario , Humanos , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/complicaciones , Estudios de Cohortes , Fallo Hepático Agudo/complicaciones , Hepatitis/complicacionesRESUMEN
BACKGROUND: Inhaled sedation during invasive mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) has received increasing attention. However, inhaled sedation devices increase dead-space ventilation and an undesirable effect is the increase in minute ventilation needed to maintain CO2 removal. A consequence of raising minute ventilation is an increase in mechanical power (MP) that can promote lung injury. However, the effect of inhaled sedation devices on MP remains unknown. METHODS: We conducted a bench study to assess and compare the effects of three devices delivering inhaled sevoflurane currently available in ICU (AnaConDa-50 mL (ANA-50), AnaConDa-100 mL (ANA-100), and MIRUS) on MP by using a test lung model set with three compliances (20, 40, and 60 mL/cmH2O). We simulated lung-protective ventilation using a low tidal volume and two levels of positive end-expiratory pressure (5 and 15 cmH2O) under ambient temperature and dry conditions. Following the insertion of the devices, either the respiratory rate or tidal volume was increased in 15%-steps until end-tidal CO2 (EtCO2) returned to the baseline value. MP was calculated at baseline and after EtCO2 correction using a simplified equation. RESULTS: Following device insertion, the EtCO2 increase was significantly greater with MIRUS (+ 78 ± 13%) and ANA-100 (+ 100 ± 11%) than with ANA-50 (+ 49 ± 7%). After normalizing EtCO2 by adjusting minute ventilation, MP significantly increased by more than 50% with all inhaled sedation devices compared to controls. The lowest increase in MP was observed with ANA-50 (p < 0.05 versus ANA-100 and MIRUS). The Costa index, another parameter assessing the mechanical energy delivered to the lungs, calculated as driving pressure × 4 + respiratory rate, significantly increased by more than 20% in all experimental conditions. Additional experiments performed under body temperature, ambient pressure, and gas saturated with water vapor conditions, confirmed the main results with an increase in MP > 50% with all devices after normalizing EtCO2 by adjusting minute ventilation. CONCLUSION: Inhaled sedation devices substantially increased MP in this bench model of protective ventilation, which might limit their benefits in ARDS.
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Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD-/-), we investigated the effects of loss of CypD on short-term and medium-term outcomes after CA. CypD-/- mice or their wild-type (WT) littermates underwent either 5 minute CA followed by resuscitation with and/or without hypothermia at 33°C-34°C (targeted temperature reached within minutes after resuscitation), or a sham procedure. Brain and cardiac injury were assessed using echocardiography, neurological scores, MRI and biomarkers. Seven day survival was compared using Kaplan-Meier estimates. The rate of restoration of spontaneous circulation was significantly higher in CypD-/- mice (with shorter cardiac massage duration) than in WT mice (P < 0.05). Loss of CypD significantly attenuated CA-induced release of troponin and S100ß protein, and limited myocardial dysfunction at 150 minutes after CA. Loss of CypD combined with hypothermia led to the best neurological and MRI scores at 24 hours and highest survival rates at 7 days compared to other groups (P < 0.05). In animals successfully resuscitated, loss of CypD had no benefits on day 7 survival while hypothermia was highly protective. Pharmacological inhibition of CypD with cyclosporine A combined with hypothermia provided similar day 7 survival than loss of CypD combined with hypothermia. CypD is a viable target to improve success of cardiopulmonary resuscitation but its inhibition is unlikely to improve long-term outcomes, unless therapeutic hypothermia is associated.
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Paro Cardíaco , Hipotermia Inducida , Hipotermia , Animales , Biomarcadores , Peptidil-Prolil Isomerasa F , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Paro Cardíaco/terapia , Hipotermia/terapia , Hipotermia Inducida/métodos , Ratones , Ratones Noqueados , TroponinaRESUMEN
Hypothermia provides an effective neuro and cardio-protection in clinical settings implying ischemia/reperfusion injury (I/R). At the onset of reperfusion, succinate-induced reactive oxygen species (ROS) production, impaired oxidative phosphorylation (OXPHOS), and decreased Ca2+ retention capacity (CRC) concur to mitochondrial damages. We explored the effects of temperature from 6 to 37 °C on OXPHOS, ROS production, and CRC, using isolated mitochondria from mouse brain and heart. Oxygen consumption and ROS production was gradually inhibited when cooling from 37 to 6 °C in brain mitochondria (BM) and heart mitochondria (HM). The decrease in ROS production was gradual in BM but steeper between 31 and 20 °C in HM. In respiring mitochondria, the gradual activation of complex II, in addition of complex I, dramatically enhanced ROS production at all temperatures without modifying respiration, likely because of ubiquinone over-reduction. Finally, CRC values were linearly increased by cooling in both BM and HM. In BM, the Ca2+ uptake rate by the mitochondrial calcium uniporter (MCU) decreased by 2.7-fold between 25 and 37 °C, but decreased by 5.7-fold between 25 and 37 °C in HM. In conclusion, mild cold (25-37 °C) exerts differential inhibitory effects by preventing ROS production, by reverse electron transfer (RET) in BM, and by reducing MCU-mediated Ca2+ uptake rate in BM and HM.
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Encéfalo , Mitocondrias Cardíacas , Animales , Homeostasis , Ratones , Especies Reactivas de Oxígeno , RespiraciónRESUMEN
OBJECTIVES: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure. DESIGN: Randomized blinded study (animal model). SETTING: University animal research facility. SUBJECTS: Twenty-four adult male "New Zealand White" rabbits. INTERVENTIONS: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period. MEASUREMENTS AND MAIN RESULTS: Pupillary reactivity (primary outcome), levels of S100ß protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100ß protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis. CONCLUSIONS: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.
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Hemodinámica/efectos de los fármacos , Síndrome de Paro Post-Cardíaco/fisiopatología , Lactato de Sodio/farmacología , Animales , Encéfalo/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Conejos , Distribución AleatoriaAsunto(s)
COVID-19/complicaciones , Pulmón/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/diagnóstico , Ultrasonografía/métodos , Anciano , COVID-19/diagnóstico , COVID-19/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Síndrome de Dificultad Respiratoria/etiología , SARS-CoV-2RESUMEN
COVID-19 pandemic sets the healthcare system to a shortage of ventilators. We aimed at assessing tidal volume (VT) delivery and air recirculation during expiration when one ventilator is divided into 2 test-lungs. The study was performed in a research laboratory in a medical ICU of a University hospital. An ICU (V500) and a lower-level ventilator (Elisée 350) were attached to two test-lungs (QuickLung) through a dedicated flow-splitter. A 50 mL/cmH2O Compliance (C) and 5 cmH2O/L/s Resistance (R) were set in both A and B test-lungs (A C50R5 / B C50R5, step1), A C50-R20 / B C20-R20 (step 2), A C20-R20 / B C10-R20 (step 3), and A C50-R20 / B C20-R5 (step 4). Each ventilator was set in volume and pressure control mode to deliver 800mL VT. We assessed VT from a pneumotachograph placed immediately before each lung, pendelluft air, and expiratory resistance (circuit and valve). Values are median (1st-3rd quartiles) and compared between ventilators by non-parametric tests. Between Elisée 350 and V500 in volume control VT in A/B test- lungs were 381/387 vs. 412/433 mL in step 1, 501/270 vs. 492/370 mL in step 2, 509/237 vs. 496/332 mL in step 3, and 496/281 vs. 480/329 mL in step 4. In pressure control the corresponding values were 373/336 vs. 430/414 mL, 416/185 vs. 322/234 mL, 193/108 vs. 176/ 92 mL and 422/201 vs. 481/329mL, respectively (P<0.001 between ventilators at each step for each volume). Pendelluft air volume ranged between 0.7 to 37.8 ml and negatively correlated with expiratory resistance in steps 2 and 3. The lower-level ventilator performed closely to the ICU ventilator. In the clinical setting, these findings suggest that, due to dependence of VT to C, pressure control should be preferred to maintain adequate VT at least in one patient when C and/or R changes abruptly and monitoring of VT should be done carefully. Increasing expiratory resistance should reduce pendelluft volume.
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COVID-19/terapia , Respiración Artificial/métodos , Ventiladores Mecánicos/efectos adversos , Femenino , Humanos , Rendimiento Pulmonar , Mediciones del Volumen Pulmonar , Masculino , Presiones Respiratorias Máximas , Respiración Artificial/efectos adversos , Respiración Artificial/instrumentación , Ventiladores Mecánicos/normasRESUMEN
BACKGROUND: Norepinephrine is the first-line vasoactive drug in septic shock. As underdosages or overdosages can be harmful for patients, it seems useful to maintain the mean arterial pressure (MAP) within preset bounds. OBJECTIVES: We sought to assess whether adjusted MAP alarms could improve MAP control in patients with septic shock. METHODS: We conducted a quasi-experimental before-and-after study. During two consecutive periods, data on MAP control were obtained from patients with septic shock (n = 50/period) treated with norepinephrine over more than 24 h. The norepinephrine administration protocol, including prescription of the MAP target range (e.g., 65-75 mmHg), was identical during the two periods. During the first period (control group), the preset alarms of the monitor were used (i.e., low and high systolic blood pressure alarms set at 90 and 160 mmHg, respectively). During the second period, adjusted MAP alarms were implemented, with upper and lower bounds corresponding to the prescribed MAP target range (MAP-Alarm group). The primary end point was the percentage of time outside the desired MAP target range during the first 24 h of norepinephrine infusion. RESULTS: Baseline characteristics were not significantly different. The primary end point was significantly lower in the MAP-Alarm group than in the control group (25 ± 13% versus 51 ± 18%, respectively; p < 0.01). MAP was higher than the target 14 ± 11% of the time in the MAP-Alarm group versus 37 ± 17% in the control group (p < 0.01) and lower than the target 11 ± 9% of the time in the MAP-Alarm versus 21 ± 22% in the control group (p < 0.05). There was no significant difference between the two groups with regard to the dose of norepinephrine, duration of norepinephrine administration, and survival. CONCLUSIONS: These results suggest that adjusting MAP alarms to the desired MAP target range could dramatically improve the percentage of time spent within MAP targets in patients with septic shock but does not reduce exposure to norepinephrine.
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Choque Séptico , Presión Arterial , Presión Sanguínea , Humanos , Norepinefrina , Estudios Prospectivos , Choque Séptico/tratamiento farmacológicoRESUMEN
INTRODUCTION: The relationship between regurgitated and aspirated volume of clear fluids remains undetermined and may depend on anatomical factors and patient position. We aimed to assess whether head position (sniffing vs. extension position) affected this relationship in fresh human cadavers. We also determined the critical volume of water regurgitated that led to pulmonary aspiration of volume ≥ 0.8 mL kg-1 and ≥ 1.5 mL kg-1 for each head position. MATERIAL AND METHODS: Six volumes of water (40, 80, 100, 120, 150, and 200 mL) were injected each twice, in a randomised order, at a flow rate of 20 mL per second, into the oesophagus of seven fresh human cadavers lying in the supine position on a non-tilted table, with the head in the sniffing position and in the extension position. Aspirated volume was measured in the trachea, blindly to the volume injected. RESULTS: Overall, more than 85% of the regurgitated volume was aspirated into the trachea. The volume of aspirated water was significantly greater in the sniffing position than in the extension position. The cut-off volumes of water injected into the oesophagus leading to aspirated volume ≥ 0.8 mL kg-1 and ≥ 1.5 mL kg-1 were, respectively, 0.8 mL kg-1 and 1.5 mL kg-1 in the sniffing position, and 1.2 mL kg-1 and 1.8 mL kg-1 in the extension position. CONCLUSIONS: These results confirm that most of the regurgitated clear fluid enters the trachea in humans lying in the supine position on a non-tilted table, especially when the head is in the sniffing position.