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.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

An assessment of the Acute Kidney Injury Network creatinine-based criteria in patients submitted to mechanical ventilation.

BACKGROUND AND OBJECTIVES: The aim of our study was to assess the new diagnostic criteria of acute kidney injury (AKI) proposed by the Acute Kidney Injury Network (AKIN) in a large cohort of mechanically ventilated patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a prospective observational cohort study enrolling 2783 adult intensive care unit patients under mechanical ventilation (MV) with data on serum creatinine concentration (SCr) in the first 48 hours. The absolute and the relative AKIN diagnostic criteria (changes in SCr ≥ 0.3 mg/dl or ≥ 50% over the first 48 hours of MV, respectively) were analyzed separately. In addition, patients were classified into three groups according to their change in SCr (ΔSCr) over the first day on MV (ΔSCr): group 1, ΔSCr ≤ -0.3 mg/dl; group 2, ΔSCr between -0.3 and +0.29 mg/dl; and group 3, ΔSCr ≥ +0.3 mg/dl). The primary end point was in-hospital mortality, and secondary end points were intensive care unit and hospital length of stay, and duration of MV. RESULTS: Of 2783 patients, 803 (28.8%) had AKI according to both criteria: 431 only absolute (AKI(A)), 362 both relative and absolute (AKI(R+A)), and 10 only relative. The relative criterion identified more patients when baseline SCr (SCr0) was <0.9 mg/dl and the absolute when SCr0 was >1.5 mg/dl. The diagnosis of AKI was associated with mortality. CONCLUSIONS: Our study confirms the validity of the AKIN criteria in a population of mechanically patients and the criteria's relationship with the baseline SCr.

Airway pressure release ventilation versus assist-control ventilation: a comparative propensity score and international cohort study.

PURPOSE: To compare characteristics and clinical outcomes of patients receiving airway pressure release ventilation (APRV) or biphasic positive airway pressure (BIPAP) to assist-control ventilation (A/C) as their primary mode of ventilatory support. The objective was to estimate if patients ventilated with APRV/BIPAP have a lower mortality. METHODS: Secondary analysis of an observational study in 349 intensive care units from 23 countries. A total of 234 patients were included who were ventilated only with APRV/BIPAP and 1,228 patients who were ventilated only with A/C. A case-matched analysis according to a propensity score was used to make comparisons between groups. RESULTS: In logistic regression analysis, the most important factor associated with the use of APRV/BIPAP was the country (196 of 234 patients were from German units). Patients with coma or congestive heart failure as the reason to start mechanical ventilation, pH <7.15 prior to mechanical ventilation, and patients who developed respiratory failure (SOFA score >2) after intubation with or without criteria of acute respiratory distress syndrome were less likely to be ventilated with APRV/BIPAP. In the case-matched analysis there were no differences in outcomes, including mortality in the intensive care unit, days of mechanical ventilation or weaning, rate of reintubation, length of stay in the intensive care unit or hospital, and mortality in the hospital. CONCLUSIONS: In this study, the APRV/BIPAP ventilation mode is being used widely across many causes of respiratory failure, but only in selected geographic areas. In our patient population we could not demonstrate any improvement in outcomes with APRV/BIPAP compared with assist-control ventilation.

Outcomes of patients ventilated with synchronized intermittent mandatory ventilation with pressure support: a comparative propensity score study.

BACKGROUND: Few data are available regarding the benefits of one mode over another for ventilatory support. We set out to compare clinical outcomes of patients receiving synchronized intermittent mandatory ventilation with pressure support (SIMV-PS) compared with assist-control (A/C) ventilation as their primary mode of ventilatory support. METHODS: This was a secondary analysis of an observational study conducted in 349 ICUs from 23 countries. A propensity score stratified analysis was used to compare 350 patients ventilated with SIMV-PS with 1,228 patients ventilated with A/C ventilation. The primary outcome was in-hospital mortality. RESULTS: In a logistic regression model, patients were more likely to receive SIMV-PS if they were from North America, had lower severity of illness, or were ventilated postoperatively or for trauma. SIMV-PS was less likely to be selected if patients were ventilated because of asthma or coma, or if they developed complications such as sepsis or cardiovascular failure during mechanical ventilation. In the stratified analysis according to propensity score, we did not find significant differences in the in-hospital mortality. After adjustment for propensity score, overall effect of SIMV-PS on in-hospital mortality was not significant (odds ratio, 1.04; 95% CI, 0.77-1.42; P = .78). CONCLUSIONS: In our cohort of ventilated patients, ventilation with SIMV-PS compared with A/C did not offer any advantage in terms of clinical outcomes, despite treatment-allocation bias that would have favored SIMV-PS.

Comparison of US and non-US central venous catheter infection rates: evaluation of processes and indicators in infection control study.

OBJECTIVE: We sought to identify the presence or absence of international variation in central venous catheter-associated bloodstream infection (BSI) rates and to examine associated infection control practices that might underlie the differences. DESIGN: The Evaluation of Processes and Indicators in Infection Control (EPIC) study was conducted as a prospective surveillance study. SETTINGS: The study took place in intensive care units (ICUs) from 14 countries, which were from the Asian Pacific (3), Europe (7), Middle East (2), and South America (2), in addition to 41 US hospitals. METHODS: We compared the National Nosocomial Infections Surveillance catheter-associated BSI rate between the non-US and US units. We also compared the following organization factors between the 2 groups: hospital factors (ownership, average daily census of patients); ICU type (medical vs surgical); number of beds; and infection control-related factors (number of staff, number of hours spent on study ICU surveillance, years of experience, number of inservice sessions on line infection, number of blood cultures drawn/1000 patients). RESULTS: We found no significant difference in catheter-associated BSI rates between non-US and US hospitals (5.02 +/- 0.75 vs 3.82 +/- 0.42/1000 days, respectively; P =.27). Non-US hospitals were more likely to be government-owned (10/14 vs 7/41;P <.001) and to have larger daily patient census (795 +/- 84 vs 276 +/- 47 patients; P <.001). There was no difference in ICU type or number of beds. Infection control committees were present in all US and non-US hospitals. No significant differences were found in the number of staff involved in surveillance in the study ICU, years of experience, hours spent on surveillance, or the provision of inservices on line care. The use of barriers during line insertion also did not differ. CONCLUSIONS: Catheter-associated BSIs in patients in the ICU were not significantly different between non-US and US hospitals. All hospitals had infection control committees, and there were no significant differences in time spent and numbers of persons involved in ICU surveillance activities. These findings suggest that many aspects of the standards of care do not differ between the 2 groups.