SPECIAL ARTICLE Archives - Critical Care Science (CCS)
, , , Abstract
Critical Care Science. 2023;35(4):345-354
DOI 10.5935/2965-2774.20230162-en
, , , , , , , , , , , , , , , , , , , 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.
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.
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.
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.
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?’
Abstract
Critical Care Science. 2023;35(4):345-354
DOI 10.5935/2965-2774.20230162-en
, , , , , , , , , , , , , , , , , , , 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.
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.
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.
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.
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?’
, , , , , Abstract
Critical Care Science. 2023;35(3):266-272
DOI 10.5935/2965-2774.20230223-en
, , , , , , , , , , , , , The objective of this study is to present the protocol of a cluster randomized clinical trial to be conducted through the TeleICU project - Qualification of Intensive Care by Telemedicine. The study will consist of a cluster randomized clinical trial, open label, in pediatric intensive care units, with an allocation ratio of 1:1, to compare the intervention group (support of Telemedicine for patients admitted to the pediatric intensive care unit) with a control group (pediatric intensive care unit usual care). The study proposed to select 16 pediatric intensive care units, including 100 participants per site, with a total of 1,600 participants. The intervention group will receive telerounds from Monday to Friday and will have specialists and continuing education activities available. The primary outcome measure will be the length of stay in the pediatric intensive care unit, defined as the difference between the date of discharge of the participant and the date of admission to the intensive care unit. The secondary outcomes will be mortality rate, invasive mechanical ventilation-free days, days using antibiotics, days using vasoactive drugs and days using sedoanalgesia. This study will be conducted in accordance with Resolution 466/12 of the National Health Council, with approval by the Research Ethics Committee of the institutions involved. The present study has the potential to reproduce studies on Telemedicine in intensive care and may make important contributions to care in intensive care units in Brazil and other settings. If Telemedicine shows positive clinical care results compared to conventional treatment, more pediatric patients may benefit.
ClinicalTrials.gov registry: NCT05260710
Abstract
Critical Care Science. 2023;35(3):266-272
DOI 10.5935/2965-2774.20230223-en
, , , , , , , , , , , , , The objective of this study is to present the protocol of a cluster randomized clinical trial to be conducted through the TeleICU project - Qualification of Intensive Care by Telemedicine. The study will consist of a cluster randomized clinical trial, open label, in pediatric intensive care units, with an allocation ratio of 1:1, to compare the intervention group (support of Telemedicine for patients admitted to the pediatric intensive care unit) with a control group (pediatric intensive care unit usual care). The study proposed to select 16 pediatric intensive care units, including 100 participants per site, with a total of 1,600 participants. The intervention group will receive telerounds from Monday to Friday and will have specialists and continuing education activities available. The primary outcome measure will be the length of stay in the pediatric intensive care unit, defined as the difference between the date of discharge of the participant and the date of admission to the intensive care unit. The secondary outcomes will be mortality rate, invasive mechanical ventilation-free days, days using antibiotics, days using vasoactive drugs and days using sedoanalgesia. This study will be conducted in accordance with Resolution 466/12 of the National Health Council, with approval by the Research Ethics Committee of the institutions involved. The present study has the potential to reproduce studies on Telemedicine in intensive care and may make important contributions to care in intensive care units in Brazil and other settings. If Telemedicine shows positive clinical care results compared to conventional treatment, more pediatric patients may benefit.
ClinicalTrials.gov registry: NCT05260710
, , , , Abstract
Critical Care Science. 2023;35(2):117-146
DOI 10.5935/2965-2774.20230310-en
, , , , , , , , , Echocardiography in critically ill patients has become essential in the evaluation of patients in different settings, such as the hospital. However, unlike for other matters related to the care of these patients, there are still no recommendations from national medical societies on the subject. The objective of this document was to organize and make available expert consensus opinions that may help to better incorporate echocardiography in the evaluation of critically ill patients. Thus, the Associação de Medicina Intensiva Brasileira, the Associação Brasileira de Medicina de Emergência, and the Sociedade Brasileira de Medicina Hospitalar formed a group of 17 physicians to formulate questions relevant to the topic and discuss the possibility of consensus for each of them. All questions were prepared using a five-point Likert scale. Consensus was defined a priori as at least 80% of the responses between one and two or between four and five. The consideration of the issues involved two rounds of voting and debate among all participants. The 27 questions prepared make up the present document and are divided into 4 major assessment areas: left ventricular function, right ventricular function, diagnosis of shock, and hemodynamics. At the end of the process, there were 17 positive (agreement) and 3 negative (disagreement) consensuses; another 7 questions remained without consensus. Although areas of uncertainty persist, this document brings together consensus opinions on several issues related to echocardiography in critically ill patients and may enhance its development in the national scenario.
Abstract
Critical Care Science. 2023;35(2):117-146
DOI 10.5935/2965-2774.20230310-en
, , , , , , , , , Echocardiography in critically ill patients has become essential in the evaluation of patients in different settings, such as the hospital. However, unlike for other matters related to the care of these patients, there are still no recommendations from national medical societies on the subject. The objective of this document was to organize and make available expert consensus opinions that may help to better incorporate echocardiography in the evaluation of critically ill patients. Thus, the Associação de Medicina Intensiva Brasileira, the Associação Brasileira de Medicina de Emergência, and the Sociedade Brasileira de Medicina Hospitalar formed a group of 17 physicians to formulate questions relevant to the topic and discuss the possibility of consensus for each of them. All questions were prepared using a five-point Likert scale. Consensus was defined a priori as at least 80% of the responses between one and two or between four and five. The consideration of the issues involved two rounds of voting and debate among all participants. The 27 questions prepared make up the present document and are divided into 4 major assessment areas: left ventricular function, right ventricular function, diagnosis of shock, and hemodynamics. At the end of the process, there were 17 positive (agreement) and 3 negative (disagreement) consensuses; another 7 questions remained without consensus. Although areas of uncertainty persist, this document brings together consensus opinions on several issues related to echocardiography in critically ill patients and may enhance its development in the national scenario.
, , , , Abstract
Critical Care Science. 2023;35(1):2-10
DOI 10.5935/2965-2774.20230307-en
, , , , , , , , , The use of echocardiography by physicians who are not echocardiographers has become common throughout the world across highly diverse settings where the care of acutely ill patients is provided. Echocardiographic evaluation performed in a point-of-care manner can provide relevant information regarding the mechanism of causes of shock, for example, increasing the rates of correct diagnosis and allowing for faster informed decision-making than through evaluation methods. Considering that the accurate diagnosis of life-threatening situations is essential for professionals working with acutely ill patients, several international associations recommend that physicians responsible for critically ill patients acquire and develop the ability to perform bedside ultrasound examinations, including echocardiographic examinations. However, there is no consensus in the literature regarding which specific applications should be included in the list of skills for nonechocardiographer physicians. Taking into account the multiplicity of applications of echocardiography in different scenarios related to acutely ill patients; the differences in the published protocols, with regard to both the teaching methodology and competence verification; and the heterogeneity of training among highly diverse specialties responsible for their care at different levels, this consensus document aimed to reflect the position of representatives of related Brazilian medical societies on the subject and may thus serve as a starting point both for standardization among different specialties and for the transmission of knowledge and verification of the corresponding competencies.
Abstract
Critical Care Science. 2023;35(1):2-10
DOI 10.5935/2965-2774.20230307-en
, , , , , , , , , The use of echocardiography by physicians who are not echocardiographers has become common throughout the world across highly diverse settings where the care of acutely ill patients is provided. Echocardiographic evaluation performed in a point-of-care manner can provide relevant information regarding the mechanism of causes of shock, for example, increasing the rates of correct diagnosis and allowing for faster informed decision-making than through evaluation methods. Considering that the accurate diagnosis of life-threatening situations is essential for professionals working with acutely ill patients, several international associations recommend that physicians responsible for critically ill patients acquire and develop the ability to perform bedside ultrasound examinations, including echocardiographic examinations. However, there is no consensus in the literature regarding which specific applications should be included in the list of skills for nonechocardiographer physicians. Taking into account the multiplicity of applications of echocardiography in different scenarios related to acutely ill patients; the differences in the published protocols, with regard to both the teaching methodology and competence verification; and the heterogeneity of training among highly diverse specialties responsible for their care at different levels, this consensus document aimed to reflect the position of representatives of related Brazilian medical societies on the subject and may thus serve as a starting point both for standardization among different specialties and for the transmission of knowledge and verification of the corresponding competencies.
, , , , , Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):96-106
DOI 10.5935/0103-507X.20220004-en
, , , , , , , , , Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock.
The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy.
If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.
Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):96-106
DOI 10.5935/0103-507X.20220004-en
, , , , , , , , , Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock.
The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy.
If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.
, , , , , Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):87-95
DOI 10.5935/0103-507x.20220003-en
, , , , , , , , , , , , , , , , The TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) trial aims to assess whether a complex telemedicine intervention in intensive care units, which focuses on daily multidisciplinary rounds performed by remote intensivists, will reduce intensive care unit length of stay compared to usual care.
The TELESCOPE trial is a national, multicenter, controlled, open label, cluster randomized trial. The study tests the effectiveness of daily multidisciplinary rounds conducted by an intensivist through telemedicine in Brazilian intensive care units. The protocol was approved by the local Research Ethics Committee of the coordinating study center and by the local Research Ethics Committee from each of the 30 intensive care units, following Brazilian legislation. The trial is registered with ClinicalTrials. gov (NCT03920501). The primary outcome is intensive care unit length of stay, which will be analyzed accounting for the baseline period and cluster structure of the data and adjusted by prespecified covariates. Secondary exploratory outcomes included intensive care unit performance classification, in-hospital mortality, incidence of nosocomial infections, ventilator-free days at 28 days, rate of patients receiving oral or enteral feeding, rate of patients under light sedation or alert and calm, and rate of patients under normoxemia.
According to the trial’s best practice, we report our statistical analysis prior to locking the database and beginning analyses. We anticipate that this reporting practice will prevent analysis bias and improve the interpretation of the reported results.
Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):87-95
DOI 10.5935/0103-507x.20220003-en
, , , , , , , , , , , , , , , , The TELE-critical Care verSus usual Care On ICU PErformance (TELESCOPE) trial aims to assess whether a complex telemedicine intervention in intensive care units, which focuses on daily multidisciplinary rounds performed by remote intensivists, will reduce intensive care unit length of stay compared to usual care.
The TELESCOPE trial is a national, multicenter, controlled, open label, cluster randomized trial. The study tests the effectiveness of daily multidisciplinary rounds conducted by an intensivist through telemedicine in Brazilian intensive care units. The protocol was approved by the local Research Ethics Committee of the coordinating study center and by the local Research Ethics Committee from each of the 30 intensive care units, following Brazilian legislation. The trial is registered with ClinicalTrials. gov (NCT03920501). The primary outcome is intensive care unit length of stay, which will be analyzed accounting for the baseline period and cluster structure of the data and adjusted by prespecified covariates. Secondary exploratory outcomes included intensive care unit performance classification, in-hospital mortality, incidence of nosocomial infections, ventilator-free days at 28 days, rate of patients receiving oral or enteral feeding, rate of patients under light sedation or alert and calm, and rate of patients under normoxemia.
According to the trial’s best practice, we report our statistical analysis prior to locking the database and beginning analyses. We anticipate that this reporting practice will prevent analysis bias and improve the interpretation of the reported results.
, , , , , Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):44-55
DOI 10.5935/0103-507X.20220002-en
, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial.
ClinicalTrials.gov identifier:
Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):44-55
DOI 10.5935/0103-507X.20220002-en
, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial.
ClinicalTrials.gov identifier:
, , , , , Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):1-12
DOI 10.5935/0103-507X.20220001-en
, , , , , , , , , , , , , , , , , , , , , , , Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil.
A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method.
Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made.
To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.
Abstract
Revista Brasileira de Terapia Intensiva. 2022;34(1):1-12
DOI 10.5935/0103-507X.20220001-en
, , , , , , , , , , , , , , , , , , , , , , , Several therapies are being used or proposed for COVID-19, and many lack appropriate evaluations of their effectiveness and safety. The purpose of this document is to develop recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil.
A group of 27 experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method.
Sixteen recommendations were generated. They include strong recommendations for the use of corticosteroids in patients using supplemental oxygen, the use of anticoagulants at prophylactic doses to prevent thromboembolism and the nonuse of antibiotics in patients without suspected bacterial infection. It was not possible to make a recommendation regarding the use of tocilizumab in patients hospitalized with COVID-19 using oxygen due to uncertainties regarding the availability of and access to the drug. Strong recommendations against the use of hydroxychloroquine, convalescent plasma, colchicine, lopinavir + ritonavir and antibiotics in patients without suspected bacterial infection and also conditional recommendations against the use of casirivimab + imdevimab, ivermectin and rendesivir were made.
To date, few therapies have proven effective in the treatment of hospitalized patients with COVID-19, and only corticosteroids and prophylaxis for thromboembolism are recommended. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and promote economical resource use.
