Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study.

INTRODUCTION: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. METHODS: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. RESULTS: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (p = .819 and p = .265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. CONCLUSION: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

[Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study]. / Eficacia de la tromboprofilaxis con heparina de bajo peso molecular en pacientes críticos con COVID-19: estudio observacional, prospectivo y multicéntrico.

Introduction: COVID-19 induces coagulopathy associated with an increase of thromboembolic events. Due to the lack of agreement on recommendations for thromboprophylactic management, the aim of this study was to study the dosages of LMWH used in critically ill COVID-19 patients assessing the effect on their outcome. Metohds: We evaluated data of the Reg-COVID19. According to LMWH dose two groups were analyzed: prophylaxis and treatment. Primary outcome was the relationship of LMWH dosage with mortality. Secondary outcomes included the incidence of thrombotic and bleeding events, length of ICU stay, invasive mechanical ventilation, and thrombotic and inflammatory parameters. Results: Data of 720 patients were analyzed, 258 in the prophylaxis group and 462 in the treatment group. C Reactive Protein, invasive mechanical ventilation, tocilizumab and corticosteroid treatments were related with the choice of LMWH dose. Hemorrhagic events (66/720, 9.2%) and thrombotic complications (69/720, 9.6%) were similar in both groups (P=.819 and P=.265), as was the time course of the thrombotic events, earlier than hemorrhagic ones (9 [3-18] and 12 [6-19] days respectively). Mortality was lower in prophylaxis group (25.2% versus 35.1%), but once an inverse probability weighting model was applied, we found no effect of LMWH dose. Conclusion: We found no benefit or harm with the administration of therapeutic or prophylactic LMWH dose in COVID19 critically ill patients. With a similar rate of hemorrhagic or thrombotic events, the LMWH dose had no influence on mortality. More studies are needed to determine the optimal thromboprophylaxis protocol for critically ill patients.

Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico / Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: a prospective, cohort, multicentre study

ANTECEDENTES: No se ha reportado plenamente la evolución clínica de los pacientes críticos de COVID-19 durante su ingreso en la unidad de cuidados intensivos (UCI), incluyendo las complicaciones médicas e infecciosas y terapias de soporte, así como su asociación con la mortalidad en ICU. OBJETIVO: El objetivo de este estudio es describir las características clínicas y la evolución de los pacientes ingresados en UCI por COVID-19, y determinar los factores de riesgo de la mortalidad en UCI de dichos pacientes. MÉTODOS: Estudio prospectivo, multi-céntrico y de cohorte, que incluyó a los pacientes críticos de COVID-19 ingresados en 30 UCIs de España y Andorra. Se incluyó a los pacientes consecutivos de 12 de Marzo a 26 de Mayo de 2020 si habían fallecido o habían recibido el alta de la UCI durante el periodo de estudio. Se reportaron los datos demográficos, síntomas, signos vitales, marcadores de laboratorio, terapias de soporte, terapias farmacológicas, y complicaciones médicas e infecciosas, realizándose una comparación entre los pacientes fallecidos y los pacientes dados de alta. RESULTADOS: Se incluyó a un total de 663 pacientes. La mortalidad general en UCI fue del 31% (203 pacientes). Al ingreso en UCI los no supervivientes eran más hipoxémicos [SpO2 sin mascarilla de no reinhalación, de 90 (RIC 83-93) vs 91 (RIC 87-94); p < 0,001] y con mayor puntuación en la escala SOFA - Evaluación de daño orgánico secuencial - [SOFA, 7 (RIC 5-9) vs 4 (RIC 3-7); p < 0,001]. Las complicaciones fueron más frecuentes en los no supervivientes: síndrome de distrés respiratorio agudo (SDRA) (95% vs 89%; p = 0,009), insuficiencia renal aguda (IRA) (58% vs 24%; p < 10−16), shock (42% vs 14%; p < 10−13), y arritmias (24% vs 11%; p < 10−4). Las súper-infecciones respiratorias, infecciones del torrente sanguíneo y los shock sépticos fueron más frecuentes en los no supervivientes (33% vs 25%; p = 0,03, 33% vs 23%; p = 0,01 y 15% vs 3%, p = 10−7), respectivamente. El modelo de regresión multivariable reflejó que la edad estaba asociada a la mortalidad, y que cada año incrementaba el riesgo de muerte en un 1% (95%IC: 1-10, p = 0,014). Cada incremento de 5 puntos en la escala APACHE II predijo de manera independiente la mortalidad [OR: 1,508 (1,081, 2,104), p = 0,015]. Los pacientes con IRA [OR: 2,468 (1,628, 3,741), p < 10−4)], paro cardiaco [OR: 11,099 (3,389, 36,353), p = 0,0001], y shock séptico [OR: 3,224 (1,486, 6,994), p = 0,002] tuvieron un riesgo de muerte incrementado. CONCLUSIONES: Los pacientes mayores de COVID-19 con puntuaciones APACHE II más altas al ingreso, que desarrollaron IRA en grados II o III y/o shock séptico durante la estancia en UCI tuvieron un riesgo de muerte incrementado. La mortalidad en UCI fue del 31%

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83-93) vs 91 (IQR 87-94); p < 0.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5-9) vs 4 (IQR 3-7); p < 0.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs 89%; p = 0.009), acute kidney injury (AKI) (58% vs 24%; p < 10−16), shock (42% vs 14%; p < 10−13), and arrhythmias (24% vs 11%; p < 10−4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs 25%; p = 0.03, 33% vs 23%; p = 0.01 and 15% vs 3%, p = 10−7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1-10, p = 0.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), p = 0.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), p < 10−4)], cardiac arrest [OR: 11.099 (3.389, 36.353), p = 0.0001], and septic shock [OR: 3.224 (1.486, 6.994), p = 0.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades II or III and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%

Patient characteristics, clinical course and factors associated to ICU mortality in critically ill patients infected with SARS-CoV-2 in Spain: A prospective, cohort, multicentre study. / Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multicéntrico.

BACKGROUND: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. OBJECTIVE: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. METHODS: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. RESULTS: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001]. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10-16), shock (42% vs. 14%; P<10-13), and arrhythmias (24% vs. 11%; P<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), P=.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), P<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), P=.0001], and septic shock [OR: 3.224 (1.486, 6.994), P=.002] had an increased risk-of-death. CONCLUSIONS: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.