Open access Original research BMJ Open: first published as 10.1136/bmjopen-2020-044357 on 15 July 2021. Downloaded from Local anaesthetics combined with vasoconstrictors in patients with cardiovascular disease undergoing dental procedures: systematic review and meta- analysis Caio Chaves Guimaraes ,1 Luciane Cruz Lopes ,2 Cristiane de Cássia Bergamaschi ,2 Juliana Cama Ramacciato,3 Marcus Tolentino Silva ,2 Jimmy de Oliveira Araújo,1 Natalia Karol de Andrade,1 Rogério Heládio Lopes Motta 3 To cite: Guimaraes CC, ABSTRACT Strengths and limitations of this study Lopes LC, Bergamaschi CdC, Objectives There is a lack of evidence about the use of et al. Local anaesthetics local anaesthetics (LAs) in patients with cardiovascular ► This review was conducted with methodological combined with vasoconstrictors diseases (CVD) in dental procedures. Thus, this study in patients with cardiovascular rigour, including assessment of the risk of bias and evaluated the safety of using LA with vasoconstrictor to disease undergoing dental the quality of evidence; such information is not determine the risk of cardiovascular events in patients procedures: systematic review available in previous systematic reviews related to with CVD. and meta- analysis. BMJ Open the subject. 2021;11:e044357. doi:10.1136/ Design Systematic review and meta- analysis. ► This study has explicit eligibility criteria, priority Methods We have searched in Cochrane Central Register bmjopen-2020-044357 of primary and secondary outcomes, comprehen- of Controlled Trials (CENTRAL), MEDLINE (via Ovid), Prepublication history and sive and extensive search in the databases, with ► EMBASE (via Ovid), Healthstar (via Ovid), CINAHL, Web of additional supplemental material independent and peer reviews for each study and Science and ClinicalTrials. gov for randomised controlled for this paper are available use of Grading of Recommendations Assessment, trials (RCTs) up to January 2020. We have included RCTs online. To view these files, Development and Evaluation to assess the quality of http://bmjopen.bmj.com/ involving adults with CVD within two groups: intervention please visit the journal online. the evidence and the strength of recommendation group with LA with vasoconstrictor and control group To view these files, please visit for the outcomes included in the meta-analysis. the journal online (http:// dx. doi. with LA without vasoconstrictor. The primary outcomes ► The primary studies included were a limiting factor org/ 10. 1136/ bmjopen- 2020- assessed were death, mortality by a specific cause, for the findings of this review due to methodological 044357). stroke, acute myocardial infarction, hospitalisation, pain, bias observed in the included randomised controlled bleeding and arrhythmias. The secondary outcomes were Received 21 September 2020 trials, as well as the differences observed in the ST segment depression, anxiety, adverse effects and Accepted 15 June 2021 types of cardiovascular diseases, types and dosages changes in haemodynamic parameters. The data were of local anaesthetics and vasoconstrictors. pooled using random effects meta-analyses and the on September 26, 2021 by guest. Protected copyright. confidence in the estimates was verified using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). INTRODUCTION Results Ten RCTs (n=478 participants) were included. Cardiovascular diseases (CVD) are one of the Most of them had a high risk of bias. There were causes of most premature deaths worldwide, more cases of pain and bleeding in groups without representing 31% of all deaths. It is estimated vasoconstrictor. Meta- analysis demonstrated a decrease in the systolic blood pressure with the use of LA with that in 2012 CVD were the main cause of death vasoconstrictor (standard mean difference −0.95, 95% CI in the world with approximately 17.5 million © Author(s) (or their −1.35 to −0.55) after procedure. Overall, for the other deaths. In 2002, three- quarters of CVD deaths employer(s)) 2021. Re- use occurred in low-income or middle-income permitted under CC BY-NC. No outcomes assessed there was no statistical difference. The commercial re- use. See rights quality of evidence was considered low according to the countries. CVD comprises essential hyper- and permissions. Published by GRADE profile. tension, rheumatic heart diseases, ischaemic BMJ. Conclusions The results suggest that the use of LA with heart diseases, cerebrovascular diseases, heart For numbered affiliations see vasoconstrictors (epinephrine in low doses) is safe in inflammatory diseases and so forth.1 end of article. patients with some types of CVD. However, the low quality In the dental office, the presence of of evidence demonstrated that literature needs further patients with complex diseases such as CVD Correspondence to studies in order to confirm these results. is increasingly common. These patients have Caio Chaves Guimaraes; Protocol registration PROSPERO (CRD42016045421). drcaio_ cg@ hotmail. com access to better treatments and medications, Guimaraes CC, et al. BMJ Open 2021;11:e044357. doi:10.1136/bmjopen-2020-044357 1 Open access BMJ Open: first published as 10.1136/bmjopen-2020-044357 on 15 July 2021. Downloaded from http://bmjopen.bmj.com/ Figure 1 Flow chart for literature search and study selection. CVD, cardiovascular disease; RCT, randomised controlled trial. which makes it possible to perform treatment in private These systemic adverse effects are linked to inadequate dental clinics that previously was only executed by special- procedures such as intravascular injection, high-dose ised hospitals.2 3 However, careful evaluations should be injections, drug interactions or instant absorption of the on September 26, 2021 by guest. Protected copyright. conducted before beginning dental treatment in patients anaesthetic agent when it is injected into an extremely with CVD in order to control stress and mainly to block vascular area that could induce adverse cardiovascular nerve transmission of pain, thereby minimising tran- effects, especially in patients with CVD.3 8–10 sient episodes that may trigger negative cardiovascular Another factor for adverse effects is the concentration outcomes.3 used in LAs. Currently, a greater dilution of the vasocon- The use of local anaesthetics (LAs) and analgesics can strictor is recommended, mostly used at a concentration control pain, while sedatives control the anxiety during of 1:100 000 for surgical procedures and, for other proce- dental procedures.3 4 However, the use of LA has been the dures, with a dilution of up to 1:200 000.2 6 Nevertheless, baseline of pain control for dental procedures for several for long and/or surgical procedures, LAs without vasocon- decades.5 6 strictor do not offer a satisfactory anaesthetic duration, LAs are combined with vasoconstrictors to increase which can cause pain resulting in systemic endogenous duration of anaesthetic effect, reduce systemic toxicity release of catecholamines (particularly norepinephrine) and optimise soft tissue haemostasis.6 However, despite the and causing negative cardiovascular outcomes.11–13 beneficial properties of vasoconstrictors when combined A previous study reported that the stress- induced with LAs, dental professionals are concerned about the release of catecholamines could be >10 times greater than adverse effects associated with the vasoconstrictor, mainly the basal level.14 In stressful situations, such as pain and with epinephrine, which is the most used vasoconstrictor anxiety, the released endogenous catecholamines may also in dentistry.2 7 reach concentrations higher than the low epinephrine 2 Guimaraes CC, et al. BMJ Open 2021;11:e044357. doi:10.1136/bmjopen-2020-044357 Open access BMJ Open: first published as 10.1136/bmjopen-2020-044357 on 15 July 2021. Downloaded from METHODS AND ANALYSES The systematic review was performed according to the recommendations specified in the Cochrane Handbook for Interventional Reviews and reported according to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses statement.18 Protocol and registration The protocol of this systematic review was registered on the PROSPERO—International Prospective Register of System- atic Reviews (registration number CRD42016045421). Eligibility criteria Inclusion criteria Patients Adult patients with CVD (essential hypertension, rheu- matic heart diseases, ischaemic heart diseases, cerebrovas- cular diseases, and heart inflammatory diseases).1 Interventions One arm wherein patients received LA with vasocon- strictors compared with another arm wherein patients received LAs without vasoconstrictors. Procedures Patients who undergo tooth extraction, dental resto- rations, treatment and periodontal surgery, among others. Figure 2 Risk of bias summary: review authors’ judgements. Type of study Considering that observational studies increase the risk concentrations used in dental LA.14 15 Thus, the literature of bias to answer this question, the study design that can generate high quality evidence, according to the recommends using the lowest effective concentration of http://bmjopen.bmj.com/ epinephrine as possible for patients with CVD, both for evidence hierarchy, would be the randomised controlled dermatological and dental procedures.9 13 A few decades trials (RCTs). We include two types of RCT designs. In the ago, the maximum dose of epinephrine in patients with first type, patients are randomised to receive either LAs cardiovascular disease was set at up to