Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock The ANDROMEDA-SHOCK Randomized Clinical Trial

Importance Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality. Design, Setting, and Participants Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock : The ANDROMEDA-SHOCK Randomized Clinical Trial

IMPORTANCE: Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. OBJECTIVE: To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. INTERVENTIONS: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. RESULTS: Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. CONCLUSIONS AND RELEVANCE: Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.Facultad de Ciencias Médica

Manejo del paciente en shock séptico

El shock séptico es la manifestación más grave de una infección. Esta se produce como consecuencia de una respuesta inflamatoria sistémica severa que lleva a un colapso cardiovascular y/o microcirculatorio, y a hipoperfusión tisular. La hipoperfusión constituye el elemento central que define la condición de shock y esta debe ser detectada y revertida en forma urgente desde la atención inicial. La evaluación de la perfusión periférica, la diuresis, y la medición del lactato y de la saturación venosa central, son las principales herramientas para evaluar la perfusión sistémica. La reanimación debe comenzar en forma inmediata con la administración agresiva de fluidos, la cual puede ser guiada por parámetros dinámicos de respuesta a fluidos, y continuada hasta normalizar u optimizar las metas de perfusión. En forma paralela se debe iniciar vasopresores en caso de hipotensión marcada, siendo el agente de elección noradrenalina, y conectar precozmente al paciente a ventilación mecánica frente a hipoperfusión severa que no responde a fluidos, o frente a un aumento del trabajo respiratorio. Adicionalmente, el foco infeccioso debe ser tratado agresivamente iniciando antibióticos lo antes posible

Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebocontrolled, double-blind, crossover study

Artículo de publicación ISIPurpose: The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation. Methods: We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixeddose) or placebo in 20 septic shock patients with cardiac index C2.5 l/ min/m2 and hyperlactatemia. Primary outcome was sublingual perfused microvascular density. Results: Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9–10.1) vs. 9.1 n/mm (7.9–9.9); p = 0.24] or microvascular flow index [2.1 (1.8–2.5) vs. 2.1 (1.9–2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venousarterial pCO2 gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO2 gradient. The indocyanine green plasma disappearance rate [14.4 (9.5–25.6) vs. 18.8 %/min (11.7–24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1–3.1) vs. 2.5 %/s (1.2–3.4); p = 0.01] were worse with dobutamine compared to placebo. Conclusions: Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.FONDECYT Chile, Project 110061

Hypoxia-related parameters during septic shock resuscitation: Pathophysiological determinants and potential clinical implications

Background: Assessment of tissue hypoxia at the bedside has yet to be translated into daily clinical practice in septic shock patients. Perfusion markers are surrogates of deeper physiological phenomena. Lactate-to-pyruvate ratio ( LPR) and the ratio between veno-arterial PCO2 difference and Ca-vO(2) (Delta PCO2/Ca-vO(2)) have been proposed as markers of tissue hypoxia, but they have not been compared in the clinical scenario. We studied acute septic shock patients under resuscitation. We wanted to evaluate the relationship of these hypoxia markers with clinical and biochemical markers of hypoperfusion during septic shock resuscitation. Methods: Secondary analysis of a randomized controlled trial. Septic shock patients were randomized to fluid resuscitation directed to normalization of capillary refill time (CRT) versus normalization or significant lowering of lactate. Multimodal assessment of perfusion was performed at 0, 2, 6 and 24 hours, and included macrohemodynamic and metabolic perfusion variables, CRT, regional flow and hypoxia markers. Patients who attained their pre-specified endpoint at 2-hours were compared to those who did not. Results: Forty-two patients were recruited, median APACHE-II score was 23 [15-31] and 28-day mortality 23%. LPR and Delta PCO2/Ca-vO(2) ratio did not correlate during early resuscitation (0-2 h) and the whole study period (24-hours). Delta PCO2/Ca-vO(2) ratio derangements were more prevalent than LPR ones, either in the whole cohort (52% vs. 23%), and in association with other perfusion abnormalities. In patients who reached their resuscitation endpoints, the proportion of patients with altered Delta PCO2/Ca-vO(2) ratio decreased significantly (66% to 33%, P=0.045), while LPR did not (14% vs. 25%, P=0.34). Conclusions: Hypoxia markers did not exhibit correlation during resuscitation in septic shock patients. They probably interrogate different pathophysiological processes and mechanisms of dysoxia during early septic shock. Future studies should better elucidate the interaction and clinical role of hypoxia markers during septic shock resuscitation.Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECYT 117004

Cardiac function in critically ill patients with severe COVID: A prospective cross-sectional study in mechanically ventilated patients

Purpose: To evaluate cardiac function in mechanically ventilated patients with COVID-19. Materials and methods: Prospective, cross-sectional multicenter study in four university-affiliated hospitals in Chile. All consecutive patients with COVID-19 ARDS requiring mechanical ventilation admitted between April and July 2020 were included. We performed systematic transthoracic echocardiography assessing right and left ventricular function within 24 h of intubation. Results: 140 patients aged 57 ± 11, 29% female were included. Cardiac output was 5.1 L/min [IQR 4.5–6.2] and 86% of the patients required norepinephrine. ICU mortality was 29% (40 patients). Fifty-four patients (39%) exhibited right ventricle dilation out of whom 20 patients (14%) exhibited acute cor pulmonale (ACP). Eight out of the twenty patients with ACP exhibited pulmonary embolism (40%). Thirteen patients (9%) exhibited left ventricular systolic dysfunction (ejection fraction <45%). In the multivariate analysis acute cor pulmonale and PaO2/FiO2 ratio were independent predictors of ICU mortality. Conclusions: Right ventricular dilation is highly prevalent in mechanically ventilated patients with COVID-19 ARDS. Acute cor pulmonale was associated with reduced pulmonary function and, in only 40% of patients, with co-existing pulmonary embolism. Acute cor pulmonale is an independent risk factor for ICU mortality

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p &lt; 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p &lt; 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p &lt; 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease