Title	Research Fails to Provide Recommended Limit of Epinephrine in Local Anesthetics Used in Cardiovascular-Compromised Patients for Dental Procedures
Clinical Question	In patients with cardiovascular disease, is there an increased risk of adverse reactions when greater than 0.04 mg of epinephrine is delivered with local anesthetic per appointment?
Clinical Bottom Line	The research available is unclear in terms of a proven specific amount of epinephrine in local anesthetics that can be used without any complications. Endogenous epinephrine can be released due to stress of the dental procedure itself, which is an extraneous factor that cannot be standardized between patients. Therefore, it is important to monitor pain and stress during a dental procedure for cardiovascular patients undergoing dental treatment in order to decrease the amount of endogenous epinephrine released. There is not sound research supporting the threshold of epinephrine use in cardiac patients, mostly because it would be unethical to subject patients of a toxic dose of epinephrine. Lastly, the ischemic changes seen are not life threatening, but the dentist should still be aware.
Best Evidence
PubMed ID Author / Year Patient Group Study type (level of evidence) 12142870 Bader/2002 325 patients total in 6 studies; 177 hypertensive patients, of which 14% were taking anti-hypertensive medications Systematic review of non-randomized trials Key results In this review, patients with hypertension (HTN) were compared to patients without hypertension (NTN). The review focused mainly on changes in blood pressure and heart rate as adverse events following delivery of anesthetic with or without epinephrine. Mean changes in systolic and diastolic blood pressure and heart rate were noticed among all groups (HTN + EPI, HTN – EPI, NTN + EPI, NTN – EPI); however these changes were not statistically significant when hypertensive patients were compared to normotensive patients. Three of the studies reported premature ventricular contractions (PVCs) associated with epinephrine, but only one of these studies was in hypertensive patients. Additionally, five studies reported adverse reactions in normotensive patients. Lastly, one study reported a single episode of atrial fibrillation in a controlled hypertensive patient on medication. 18485309 Elad/2008 50 cardiovascular patients Randomized Controlled Trial Key results This randomized control trial compared the use of 4% articaine with 1:200,000 adrenalin (epinephrine) to 2% lidocaine with 1:100,000 adrenaline. Each group was administered 1.8 mL local anesthetic to complete a simple dental filling. The study compared heart rate, systolic and diastolic blood pressure, and oxygen saturation amongst the two groups. No statistically significant differences were found between the groups in any of these factors. Amongst the 50 patients included in the trial, three developed asymptomatic ischemic changes noted by ECG, two in the articaine group and one in the lidocaine group—which the study reported was not related to the local anesthetic. Although a small sample size was used, the study concluded that there were no risks associated with the use of either anesthetic agent (.018 mg/ml epinephrine in lidocaine and .009mg/ml epinephrine in articaine) in patients with cardiovascular disease. 24608362 Godzieba/2014 560 patients total in 11 studies - 6 RCTs and 5 CCTs Systematic review of randomized trials Key results This systematic review included 11 studies that studied the effects of local anesthetic containing a vasoconstrictor on patients with cardiovascular disease. Patient cardiovascular issues included hypertension, vascular disease, coronary ischemia, and valvular heart disease. The representative sample of patients included males over 50. The study found that the most common complication of local anesthetics with vasoconstrictors elicited a disclosed ECG arrhythmia, a majority being clinically insignificant. The study recommended less than or equal to 4 ampules of lignocaine (lidocaine) with epinephrine 1:100,000 as safe for cardiovascular compromised patients, and recommended ECG monitoring if more anesthetic is to be used.
Evidence Search	("Anesthesia, Local"[Mesh]) AND "Vasoconstrictor Agents"[Mesh] ("Anesthetics, Local/adverse effects"[Mesh]) AND "Vasoconstrictor Agents/adverse effects"[Mesh]
Comments on The Evidence	None of the studies presented state a specific amount of epinephrine in local anesthetics that has been proven through research to be safe or unsafe for patients of compromised cardiovascular status. Additionally, the studies lacking a comparison (Elad and Godzieba) to normotensive patients may reduce the validity of these studies due to the absence of a comparison group. The effects of epinephrine in normal non-cardiac patients should be noted in order to determine a clear effect of the epinephrine. Extraneous factors such as dental anxiety, complexity of procedure, and pain threshold cannot be exactly standardized between patients. More precise studies are needed in order to recommend a safe threshold for epinephrine use in cardiovascular patients. Overall, the systematic review by Godzieba reports a low risk of bias in its included studies. However, Bader reports that "the quantity and quality of the pertinent literature is problematic" and the evidence available is not sufficient to draw a definite conclusion concerning the safe amount of epinephrine that can be delivered in patients with cardiovascular disease; he further states that more research is necessary to determine the specific amount deemed safe for use.
Applicability	The subject pools discussed in all three of the articles presented are representative of a patient that would be seen by a dentist of any specialty. Hypertensive patients are especially prevalent in the South Texas population. In general, there is not a specific limit of epinephrine that can be used without detrimental effects proved by research. However, the recommended amounts reported by Elad are 0.018 mg/ml epinephrine in lidocaine or 0.009 mg/ml epinephrine in articane; by Godzieba, 4 ampules of lignocaine (lidocaine) with 1:100,000 epinephrine. These amounts are applicable to safely treat patients, and these recommendations should be followed by all dental specialties. However, using more than the recommended amount of epinephrine in cardiovascular patients could cause harm, or even death. Precautions should be taken, and additional safety measures should be available in a situation where more than the recommended amount is required to establish profound anesthesia. There is value in researching this topic further in order to establish sound evidence; however, there may be ethical boundaries that inhibit this type of study from being conducted. It is not ethical to subject human patients to fatal amounts of epinephrine; therefore animal studies may be indicated.
Specialty	(Endodontics) (General Dentistry) (Oral Surgery) (Periodontics) (Prosthodontics) (Restorative Dentistry)
Keywords	epinephrine, cardiovascular disease, local anesthesia, hypertension
ID#	3263
Date of submission	08/07/2017
E-mail	parksw@livemail.uthscsa.edu
Author	Wendi Parks
Co-author(s)
Co-author(s) e-mail
Faculty mentor	Ernie Luce, DDS
Faculty mentor e-mail	luce@uthscsa.edu
Basic Science Rationale (Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?) None available
Comments and Evidence-Based Updates on the CAT (FOR PRACTICING DENTISTS', FACULTY, RESIDENTS and/or STUDENTS COMMENTS ON PUBLISHED CATs) None available