Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis.

OBJECTIVE: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. DATA SOURCES: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. METHODS: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. PRIMARY ENDPOINT: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. DISCUSSION: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?'Protocol version 0.4 - 06/26/2023PROSPERO registration:CRD42021278869.

Lactato sérico en urgencias como factor pronóstico en pacientes con sepsis sin hipotensión / Serum lactate in the emergency department as a prognostic factor in patients with sepsis without hypotension

Fundamento y objetivo: La relación del lactato y la mortalidad en sepsis no ha sido explorada adecuadamente en el paciente normotenso. Nuestro objetivo fue determinar la utilidad del lactato como factor pronóstico de mortalidad a los 28 días en pacientes admitidos en el Servicio de Urgencias con diagnóstico clínico de sepsis y sin shock séptico. Pacientes y método: Análisis secundario del estudio La epidemiología de la sepsis en Colombia, una cohorte prospectiva de pacientes en 10 hospitales generales de 4 ciudades de Colombia. Se incluyeron en este análisis los pacientes sin hipotensión, con disponibilidad de lactato y admitidos con infecciones adquiridas en la comunidad confirmadas con los criterios de los Centers for Disease Control and Prevention. Se realizó una regresión logística controlando para la edad, el sexo, las comorbilidades y la puntuación de gravedad. Resultados: Se incluyeron 961 pacientes, con edad media (DE) de 57,2 (21,0) años, el 54,2% eran mujeres, la puntuación SOFA (Sequential Organ Failure Assessment) promedio fue de 3,0 (2,3) y el APACHE (Acute Physiologic and Chronic Health Evaluation) de 11,1 (6,4). Se observó un buen ajuste al modelo lineal entre el lactato y el riesgo de muerte, y al ajustar por los factores de confusión el lactato se asoció de manera significativa con la mortalidad (odds ratio 1,16, intervalo de confianza del 95% 1,02-1,33). Conclusión: El valor de lactato se asocia de forma independiente y significativa con la mortalidad a los 28 días entre los pacientes con infección que se presentan en el Departamento de Urgencias sin hipotensión. Además, la mortalidad se incrementa de manera lineal con los valores de lactato sérico a partir de cualquier valor detectable (AU)

Background and objective: The relationship between lactate and mortality in patients without hypotension has not been appropriately explored. Our aim was to determine the usefulness of serum lactate as a prognostic factor of 28-day mortality in patients admitted to the Emergency Department with clinical diagnosis of sepsis without septic shock. Patients and methods: We performed a secondary analysis of the study The epidemiology of sepsis in Colombia, a prospective cohort of patients from 10 general hospitals in 4 Colombian cities. We analyzed patients without hypotension with serum lactate available and admitted with community-acquired infections, which were confirmed according to the Centers for Disease Control and Prevention CDC criteria. A logistical regression was performed adjusting for age, sex, comorbidities and severity scores. Results: We included 961 patients aged 57.2 ± 21.0 years, 54.2% were females, mean SOFA score was 3.0 ± 2.3 and APACHE score was 11.1 ± 6.4. We observed a linear relationship between serum lactate and the odds of death, and after adjustment there was a significant and independent association between lactate and mortality (odds ratio 1,16, 95% confidence interval 1.02-1.33). Conclusion: Serum lactate is independently and significantly associated with 28-day mortality among patients with infection who present to the Emergency Department without hypotension. Besides, mortality increases in a linear way with serum lactate from any detectable value (AU)