Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19: Joint guideline of Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia, Sociedade Brasileira de Reumatologia

Falavigna, Maicon; Stein, Cinara; Amaral, José Luiz Gomes do; Azevedo, Luciano Cesar Pontes de; Belli, Karlyse Claudino; Colpani, Verônica; Cunha, Clóvis Arns da; Dal-Pizzol, Felipe; Dias, Maria Beatriz Souza; Ferreira, Juliana Carvalho; Freitas, Ana Paula da Rocha; Gräf, Débora Dalmas; Guimarães, Hélio Penna; Lobo, Suzana Margareth Ajeje; Monteiro, José Tadeu; Nunes, Michelle Silva; Oliveira, Maura Salaroli de; Prado, Clementina Corah Lucas; Santos, Vania Cristina Canuto; Silva, Rosemeri Maurici da; Sobreira, Marcone Lima; Veiga, Viviane Cordeiro; Vidal, Ávila Teixeira; Xavier, Ricardo Machado; Zavascki, Alexandre Prehn; Machado, Flávia Ribeiro; Carvalho, Carlos Roberto Ribeiro de

doi:10.5935/0103-507X.20220001-en

Acessibilidade / Reportar erro

Brasil

Revista Brasileira de Terapia Intensiva

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

SPECIAL ARTICLE • Rev. bras. ter. intensiva 34 (1) • Jan-Mar 2022 • https://doi.org/10.5935/0103-507X.20220001-en copy

Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19: Joint guideline of Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia, Sociedade Brasileira de Reumatologia

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Keywords:
COVID-19; COVID-19/ drug therapy; Health planning guidelines; SARS-CoV-2; Brazil

Level	Definition	Implications
High	Strong confidence that the true effect lies close to that of the effect estimate	It is unlikely that additional trial will change the confidence in the estimation effect
Moderate	Moderate confidence in the effect estimated	Future trial may modify the confidence in the effect estimate, and also can change the estimate
Low	Limited confidence in the effect estimate.	Future trials are likely to important impact on our confidence in the estimated effect
Very low	Uncertain confidence in the effect estimate.	Any estimate of effect is uncertain

Target audience	Strong	Conditional (weak)
Policymakers	The recommendation should be adopted as a healthcare policy in most of the situations	Substantial debate required and the involvement of stakeholders
Clinicians	Most individuals would want the intervention to be indicated, and only a small number would reject this recommendation	A large portion of the individuals would want the intervention to be indicated; however, some individuals would reject this recommendation
Patients	Most of the patients should receive the recommended intervention	The clinician should acknowledge that different choices are appropriate for each patient and choose consistently with his/her values and preferences

Medication	Recommendation
Corticosteroids	Recommendation 1.1 - We recommend the use of 6 mg dexamethasone intravenously or orally once daily for 10 days in patients who are hospitalized with COVID-19 and using supplemental oxygen (strong recommendation, moderate certainty of evidence) Recommendation 1.2 - We suggest against the use corticosteroids in patients hospitalized with COVID-19 who are not using supplemental oxygen (conditional recommendation, low certainty of evidence)
Anticoagulants	Recommendation 2.1 - We recommend the use of anticoagulants at prophylactic doses for VTE in critically ill patients (those using vasoactive drugs and those undergoing renal replacement therapy, HFNC, NIV or IMV) with COVID-19 (nongraded recommendation) Recommendation 2.2 - We suggest against the use intermediate doses or therapeutic anticoagulation in critically ill COVID-19 patients (those using vasoactive drugs or undergoing renal replacement therapy, HFNC, NIV or IMV) without evidence of thromboembolism (conditional recommendation, very low certainty of evidence) Recommendation 2.3 - We suggest the use heparin or enoxaparin in therapeutic doses in noncritical patients (those with no need for vasoactive drugs, renal replacement therapy, HFNC, NIV or IMV) hospitalized with COVID-19 (conditional recommendation, very low certainty of evidence)
Antimicrobials	Recommendation 3.1 - We recommend against the use antimicrobials in patients with COVID-19 without suspected bacterial infection (nongraded recommendation)
Tocilizumab	Recommendation 4.1 - The use of tocilizumab is clinically indicated for hospitalized patients with COVID-19 using NIV or HFNC; however, it is not possible to recommend it at this time (May 2021), as this use is not indicated in the label and there are uncertainties regarding access to the drug that affect the ability to meet the potential demand (no recommendation, moderate certainty of evidence) Recommendation 4.2 - We suggest against the use tocilizumab in patients on mechanical ventilation (conditional recommendation, moderate certainty of evidence)
Chloroquine or hydroxychloroquine	Recommendation 5.1 - We recommend against the use chloroquine or hydroxychloroquine in patients hospitalized with COVID-19 (strong recommendation, moderate certainty of evidence)
Azithromycin	Recommendation 6.1 - We recommend against the use azithromycin, with or without chloroquine or hydroxychloroquine, in patients hospitalized with COVID-19 (strong recommendation, moderate certainty of evidence)
Casirivimab + imdevimab	Recommendation 7.1 - We suggest against the use casirivimab + imdevimab in patients hospitalized with COVID-19 (conditional recommendation, very low certainty of evidence)
Rendesivir	Recommendation 8.1 - We suggest against the use rendesivir in patients hospitalized with COVID-19 (conditional recommendation, low certainty of evidence)
Convalescent plasma	Recommendation 9.1 - We recommend against the use convalescent plasma in patients hospitalized with COVID-19 (strong recommendation, moderate certainty of evidence)
Ivermectin	Recommendation 10.1 - We suggest against the use ivermectin in patients hospitalized with COVID-19 (conditional recommendation, very low certainty of evidence)
Colchicine	Recommendation 11.1 - We recommend against the use colchicine in patients hospitalized with COVID-19 (strong recommendation, moderate certainty of evidence)
Lopinavir/ritonavir	Recommendation 12.1 - We recommend against the use lopinavir/ritonavir in patients hospitalized with COVID-19 (strong recommendation, moderate certainty of evidence)

Patient group/medication	Dose
Noncritical patients: therapeutic anticoagulation
Unfractionated heparin Standard dose	Start with a bolus of 80IU/kg IV + maintenance: 18IU/kg/hour Adjust according to the coagulogram, maintaining the RT between 1.5 and 2.5, according to Raschke et al.(²⁹29 Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med. 1993;119(9):874-81.)
Enoxaparin If ClCr > 30mL/minute If ClCr < 30mL/minute	1 mg/kg subcutaneously every 12 hours. Attention to weight extremes: If weight is < 40kg or > 150kg, it is suggested to monitor anti-Xa activity (0.3 - 0.7)(³⁰30 Sebaaly J, Covert K. Enoxaparin dosing at extremes of weight: literature review and dosing recommendations. Ann Pharmacother. 2018;52(9):898-909.,³¹31 Duplaga BA, Rivers CW, Nutescu E. Dosing and monitoring of low-molecularweight heparins in special populations. Pharmacotherapy. 2001;21(2):218-34.) or If BMI is > 40kg/m²: 0.7 - 0.8mg/kg. Consider a limit of 150mg/dose(³⁰30 Sebaaly J, Covert K. Enoxaparin dosing at extremes of weight: literature review and dosing recommendations. Ann Pharmacother. 2018;52(9):898-909.) Avoid. Instead, unfractionated heparin, controlled according to the coagulogram (RT of 1.5 - 2.3), is suggested(²⁹29 Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann Intern Med. 1993;119(9):874-81.)
Fondaparinux If ClCr > 20mL/minute If ClCr < 20mL/minute	< 50kg: 5mg subcutaneously, once daily 50 - 100kg: 7.5mg subcutaneously, once daily > 100kg:10mg subcutaneously, once daily ^* * Avoid fondaparinux in patients weighing less than 50kg due to the increased risk of bleeding. Between 20 - 30mL/minute, consider administering one dose every 48 hours Do not use
Critically ill patients: prophylaxis
Unfractionated heparin Standard dose Patients with BMI > 40kg Renal insufficiency (ClCr < 30mL/minute)	5,000IU subcutaneously every 8 hours 10,000IU every 12 hours 5,000IU every 12 hours
Enoxaparin Up to 80kg Between 80 and 120kg Over 120kg BMI > 50kg ClCr < 30mL/minute	40mg once a day 60mg once a day 40mg every 12 hours 60mg every 12 hours Do not use
Fondaparinux^* * Avoid fondaparinux in patients weighing less than 50kg due to the increased risk of bleeding. Standard dose Renal insufficiency (ClCr 20 to 30mL/minute) Renal insufficiency (ClCr < 20mL/minute)	2.5mg once a day 2.5mg every 48 hours Do not use

Associação de Medicina Intensiva Brasileira - AMIB Rua Arminda, 93 - Vila Olímpia, CEP 04545-100 - São Paulo - SP - Brasil, Tel.: (11) 5089-2642 - São Paulo - SP - Brazil
E-mail: rbti.artigos@amib.com.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Conflicts of interest: Presented in the Supplementary Material.