Selection of the safest local anesthetic for dental treatment in medically compromised patients: A comprehensive review

Abstract

Local anesthetics are essential in dental practice, but their systemic effects can pose significant risks for medically compromised patients. This review aims to identify and evaluate the safest local anesthetic agents for use in dental procedures in patients with systemic medical conditions to minimize adverse outcomes and improve clinical safety. To achieve this, a comprehensive literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar for studies published from January 2000 to April 2025. Thirty-five studies addressing local anesthetic use in patients with cardiovascular disease, hepatic or renal impairment, diabetes, thyroid disorders, bleeding tendencies, pregnancy, elderly populations, and amide allergies were included. Data were synthesized to develop clinical recommendations for anesthetic selection based on systemic conditions.

Lidocaine remains the standard amide anesthetic, with a strong safety profile in pregnancy and diabetes. Mepivacaine, due to minimal vasodilation, is preferred in cardiovascular and thyroid disorders. Articaine’s rapid plasma metabolism benefits patients with liver or kidney impairment. Prilocaine is effective for hepatic impairment but poses methemoglobinemia risks, especially in pregnancy. Chloroprocaine, an ester anesthetic, is recommended for patients with confirmed amide allergies. Emerging strategies, such as buffered formulations, low epinephrine anesthetics, and ultrasound guided techniques, may enhance safety in high risk groups. Local anesthetic selection must be tailored to each patient’s medical status. Mepivacaine, lidocaine, and articaine are among the safest agents for various systemic conditions. An evidence based, condition specific approach enhances safety and treatment outcomes in medically compromised dental patients.

Introduction

Local anesthetics (LAs) are indispensable in modern dental practice, providing safe and effective pain control that facilitates a wide range of dental interventions. These agents are broadly categorized into two main chemical classes: esters and amides. Among these, amide-type anesthetics—such as lidocaine, articaine, mepivacaine, prilocaine, and bupivacaine—are most commonly used in clinical dentistry due to their favorable pharmacokinetics and reduced incidence of hypersensitivity reactions compared to ester compounds.[1,2]

Each local anesthetic agent exhibits distinct onset, duration, metabolism, and toxicity profiles. Lidocaine, first introduced in the mid-twentieth century, remains the most widely used agent due to its rapid onset and intermediate duration, making it the standard reference in dental anesthesia.[3,4] Mepivacaine, characterized by minimal vasodilatory activity, is suitable for use without vasoconstrictors and is frequently selected for patients with cardiovascular contraindications.[5] Articaine, notable for its high lipid solubility and primary metabolism via plasma esterases, is increasingly favored in patients with hepatic impairment due to its reduced dependence on liver metabolism.[6,7]

The selection of local anesthetics becomes particularly critical in medically compromised patients. Systemic conditions—such as cardiovascular disease, diabetes mellitus, thyroid dysfunction, renal or hepatic impairment, coagulopathies, and pregnancy—can significantly alter both the pharmacodynamics and pharmacokinetics of local anesthetics, increasing the risk of adverse effects.[8,9,10,11,12] For example, the use of vasoconstrictors, like epinephrine in cardiovascular or hyperthyroid patients, may trigger arrhythmias or hypertensive crises,[13,14] while in patients with impaired hepatic or renal function, reduced clearance of anesthetics could elevate systemic toxicity.[6,15]

In patients with diabetes, the physiological stress of dental procedures and the use of vasoconstrictors can exacerbate hyperglycemia and cardiovascular instability.[16,17] In those with coagulopathies or undergoing anticoagulant therapy, deep nerve blocks, such as inferior alveolar or posterior superior alveolar injections, may lead to hematoma formation or, in rare cases, airway compromise.[18] Pregnant patients present additional challenges, as all local anesthetics cross the placental barrier, necessitating careful selection of agents with demonstrated fetal safety profiles.[19]

Despite the widespread use of local anesthetics in diverse clinical scenarios, the selection of the most appropriate agent for medically compromised patients often remains guided by empirical experience rather than evidence-based protocols.[20] There is a notable lack of comprehensive literature reviews addressing the selection and safety of local anesthetic agents in the dental treatment of patients with systemic diseases. Most available studies have focused on individual conditions, such as cardiovascular disease or diabetes, without providing an integrated clinical guide for broader medically compromised populations. This review aims to fill that critical gap by evaluating a wide range of systemic disorders and recommending the most appropriate local anesthetic strategies tailored to each medical scenario, based on current evidence. The ultimate goal is to provide clinicians with practical, evidence-based guidance to enhance patient safety and treatment efficacy.

Methods

This comprehensive review was conducted to evaluate the safest and most appropriate local anesthetic agents for use in dental procedures in medically compromised patients. A detailed search of the literature was carried out using multiple electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search covered studies published between January 2000 and April 2025. Search terms included combinations of keywords, such as “local anesthetics,” “dental treatment,” “systemic diseases,” “cardiovascular disease,” “renal impairment,” “liver disease,” “diabetes,” “thyroid disorders,” “pregnancy,” “bleeding disorders,” and “medically compromised patients.” Boolean operators (AND, OR) were used to refine the search strategy.

Articles were included if they addressed the use, safety, or selection of local anesthetic agents in the dental management of patients with one or more systemic diseases. Only studies published in English or with available translations and full-text access were considered. Nonhuman studies and conference abstracts were excluded.

A total of 753 records were initially retrieved. After removing 152 duplicates, 601 studies were screened by title and abstract. Of these, 534 were excluded due to irrelevance or focus on healthy populations. Sixty-seven full-text articles were assessed for eligibility. After applying the inclusion and exclusion criteria, 35 studies were included in the review. Among the 35 included articles, eight clinical observational studies (retrospective or prospective), one was a randomized controlled trial (RCT), 18 were reviews (three systematic and 15 narrative), and eight were classified as case reports, expert commentaries, or clinical guidelines. This classification helped in assessing the strength and depth of the available evidence. Data were synthesized to generate clinical recommendations for local anesthetic selection based on various systemic conditions. The process of study selection is outlined in Figure 1.

Figure 1.

Flowchart of study selection process

Results

A total of 35 studies were included in this comprehensive review. These covered a wide range of systemic conditions, including cardiovascular disease, renal and hepatic impairment, diabetes mellitus, thyroid dysfunction, pregnancy, coagulopathies, elderly patients, allergic individuals, and those with asthma or chronic pulmonary disease. The evidence revealed consistent patterns in selecting the safest local anesthetic agents, summarized in Table 1.

Table 1.

Recommended local anesthetics for medically compromised dental patients

Medical condition	Recommendation	Preferred local anesthetic	Supporting studies (Ref. No.)
Cardiovascular disease	Avoid vasoconstrictors or limit epinephrine to ≤0.04 mg; prefer vasoconstrictor-free options or alternatives like felypressin.	Plain mepivacaine, lidocaine (≤2 carpules), prilocaine with felypressin	[1,3,17,21]
Diabetes mellitus	Use lidocaine with adrenaline cautiously; monitor blood glucose and stress levels during procedures.	Lidocaine 2% with 1:100,000 epinephrine (max 2 carpules)	[2,22]
Thyroid disorders	Avoid epinephrine in uncontrolled hyperthyroidism; prefer anesthetics without vasoconstrictors.	Mepivacaine, prilocaine (plain)	[4,23]
Renal and hepatic impairment	Use agents with minimal hepatic/renal metabolism; avoid long-acting anesthetics like bupivacaine.	Articaine, reduced-dose lidocaine	[5,8,24]
Pregnancy	Use Category B anesthetics such as lidocaine; avoid prilocaine with felypressin due to fetal risks.	Lidocaine (Category B)	[10,13]
Bleeding disorders	Avoid deep nerve blocks; use infiltration with caution.	Plain lidocaine or articaine (infiltration only)	[18]
Elderly patients	Adjust dosage to account for reduced organ function; avoid long-acting agents.	Articaine, reduced-dose lidocaine	[5,9,25]
Local anesthetic allergy	If allergic to amide agents, use ester-based alternatives such as chloroprocaine; confirm with allergy testing.	Chloroprocaine	[26,27]
Asthma and pulmonary disease	Avoid metabisulfite-containing vasoconstrictors; prefer plain solutions. Monitor for methemoglobinemia with prilocaine in lung-compromised patients.	Plain lidocaine, plain mepivacaine	[1,3,28,29]

For cardiovascular disease, multiple studies (Budenz,[1] Gazal et al.,[3] Guimaraes et al.[17] and Seminario-Amez et al.[21]) emphasized limiting epinephrine to ≤0.04 mg or using vasoconstrictor-free options. Safer alternatives included plain mepivacaine, lidocaine with minimal epinephrine, and prilocaine with felypressin, which exert less adrenergic stress on the cardiovascular system. In diabetic patients, lidocaine with 1:100,000 epinephrine was considered safe when stress was minimized and glucose levels monitored (Gazal 2020[2]).

For individuals with thyroid dysfunction, especially uncontrolled hyperthyroidism, epinephrine-containing solutions were discouraged due to the risk of precipitating thyrotoxic crisis (Laszlo 2021[4]). In renal and hepatic impairment, agents, like articaine (metabolized mainly in plasma) and low-dose lidocaine, were preferred. These agents reduced systemic burden and risk of accumulation in patients with impaired organ clearance (Uppal et al.,[8] Ouanounou and Haas[5]). Pregnant patients were best managed with lidocaine (FDA Category B). Conversely, prilocaine with felypressin was contraindicated due to the risk of fetal methemoglobinemia and premature labor induction (Gunes et al.,[10] Zhou et al.[13]).

For those with bleeding disorders or under anticoagulation, infiltration techniques using articaine or lidocaine were favored over deeper nerve blocks to minimize hematoma formation (Ueda et al.[18]). In the elderly, studies emphasized a decline in hepatic and renal function with age. Articaine or low-dose lidocaine was preferred, and bupivacaine was avoided due to prolonged half-life and increased cardiotoxicity in geriatric patients (Knutsen et al. 2025,[6] Ghafoor et al.[9]). In cases of amide-type anesthetic allergy, ester-based alternatives, like chloroprocaine, were identified as safe options, especially for minor procedures in pediatric or medically fragile populations (Aslan et al.[26]).

Asthma and Pulmonary Disease: Patients with bronchial asthma or chronic obstructive pulmonary disease (COPD) require individualized anesthetic selection due to their heightened airway reactivity and sensitivity to preservatives. Epinephrine-containing local anesthetics often contain sodium metabisulfite, a preservative that may trigger bronchospasm in susceptible individuals, particularly those with sulfite sensitivity.[28,29] In such cases, the use of plain lidocaine or mepivacaine is considered safer.

Additionally, prilocaine undergoes partial pulmonary metabolism, which theoretically offers advantages in patients with hepatic insufficiency. However, its use should be approached cautiously in those with advanced pulmonary disease due to its association with methemoglobinemia, which may be exacerbated in hypoxic states.[28]

Both Budenz[1] and Gazal et al.[3] similarly emphasized the importance of preoperative evaluation in asthmatic patients and the avoidance of agents with vasoconstrictors or preservatives when necessary. Further support the use of sulfite-free formulations and stress the importance of minimizing systemic and pulmonary complications during dental procedures in patients with chronic respiratory disorders.[29]

Overall, the review supports individualized selection of mepivacaine, lidocaine, and articaine based on each patient’s systemic condition. The safest approach requires adapting drug type, dose, and vasoconstrictor content to minimize adverse outcomes in medically compromised populations.

Table 2 presents a structured clinical decision pathway that outlines the preferred selection of local anesthetic agents based on specific systemic conditions. Table 2 was developed as a concise clinical tool derived from the detailed evidence presented in Table 1. Its purpose is to provide dental practitioners—regardless of experience level—with a simplified, condition-based guideline for selecting local anesthetic agents in medically compromised patients. By summarizing key recommendations according to systemic disease categories, Table 2 serves as a practical reference that can support safe, evidence-based decision-making in routine and emergency dental procedures. The recommendations cover key categories, such as cardiovascular disease, renal and hepatic impairment, pregnancy, thyroid dysfunction, bleeding disorders, elderly patients, and individuals with known allergies to amide-based anesthetics.

Table 2.

Clinical decision table for local anesthesia selection in medically compromised patients

Medical condition	Recommended strategy (→)
Cardiovascular disease	→ Use mepivacaine or prilocaine + felypressin → Avoid high-dose vasoconstrictors
Renal or hepatic impairment	→ Use articaine → Preferred due to plasma metabolism
Pregnancy	→ Use lidocaine (Category B) → Avoid prilocaine/felypressin
Thyroid disease or diabetes	→ Use plain mepivacaine → Avoid epinephrine if disease is uncontrolled
Bleeding disorders	→ Use infiltration (Plain local anesthetic) → Avoid deep nerve blocks
Elderly patients	→ Reduce dose of lidocaine or articaine → Monitor liver/kidney function
Allergy to amide local anesthetic	→ Use ester-based local anesthetic (e.g., chloroprocaine)
Asthma/COPD (Chronic obstructive pulmonary disease)	→ Use plain mepivacaine (no vasoconstrictor) → Avoid local anesthetics with adrenaline (contain sulfite preservatives)

Discussion

This comprehensive review represents the first effort in the literature to systematically address the selection of the safest local anesthetic agents across a wide spectrum of systemic medical conditions encountered in dental practice. Unlike previous studies that focused on isolated diseases, this comprehensive review integrates evidence-based recommendations for multiple comorbidities, providing a unified reference for clinical decision-making. Most notably, it introduces the first structured protocol designed to assist dental practitioners worldwide in selecting appropriate anesthetics for medically compromised patients. The implementation of this guideline in daily clinical practice has the potential to reduce the risk of malpractice, improve patient safety, enhance treatment outcomes, and elevate the overall competency of dental professionals when managing complex medical cases in the operatory setting. The selection of the safest local anesthetic for medically compromised patients requires careful evaluation of pharmacokinetics, pharmacodynamics, and systemic impact.[30,31,32] This review aimed to synthesize current evidence regarding the use of local anesthetic agents in dental procedures involving patients with systemic diseases, aligning with the broader goal of minimizing adverse events and improving clinical outcomes. Lidocaine, the most widely used amide local anesthetic, remains the gold standard in dental practice. Its safety profile is well established, particularly in pregnant patients (FDA Category B) and diabetic patients, provided epinephrine is used cautiously and blood glucose levels are monitored.[1,4,7,10,33] Mepivacaine, known for its low vasodilatory effect, has been recommended in cardiovascular and hyperthyroid patients, where minimizing adrenergic stimulation is essential.[6,9,13,24,30] Articaine, with a rapid onset and metabolism primarily in the plasma (85–90%), has emerged as a preferred agent in patients with hepatic or renal dysfunction, where reduced organ metabolism lowers systemic toxicity.[3,5,12,15,19,34] Additionally, recent studies emphasize its suitability in the elderly, due to age-related hepatic decline. Prilocaine demonstrates a dual metabolic pathway (liver and lungs), offering an advantage in hepatic impairment but carries the risk of methemoglobinemia, especially at higher doses or in combination with felypressin. The use of prilocaine with felypressin should be avoided during pregnancy due to potential uterotonic effects.[11,16] Bupivacaine, owing to its long duration of action, is primarily reserved for postoperative pain management in extensive procedures. However, its known cardiotoxicity restricts its use in patients with cardiac comorbidities or elderly populations.[8,17] Chloroprocaine, an ester-type anesthetic, has gained renewed attention (2023–2024) as a safe alternative in patients with confirmed allergies to amide agents. Its rapid hydrolysis by plasma cholinesterase and ultra-short half-life make it an ideal choice in pediatric patients or those with hepatic/renal impairment.[18,20,32] Several innovations have improved the comfort and safety of local anesthesia delivery. Buffered local anesthetics such as buffered lidocaine and articaine have been shown to reduce injection pain and improve onset time—particularly important in diabetic and cardiovascular patients.[14,29,31] Moreover, articaine 4% with 1:400,000 epinephrine offers similar anesthetic efficacy with reduced vasoconstrictor concentration, lowering the risk of hypertension and tachycardia in sensitive individuals.[17,35] Liposomal bupivacaine (Exparel®) is under investigation for long-acting postoperative analgesia but remains limited in routine dental care due to cost and regulatory considerations. Finally, ultrasound-guided anesthetic techniques are emerging as a safer alternative for patients on anticoagulants or with bleeding disorders, reducing the likelihood of vascular injury and hematoma formation.[26]

In terms of clinical implications, the findings of this review reinforce the importance of tailoring anesthetic selection to the patient’s systemic status. A standardized clinical protocol—such as the proposed one in Table 2—can help clinicians make evidence-based decisions when managing dental procedures in high-risk populations, for instance: avoiding vasoconstrictors in cardiovascular and thyroid patients; preferring articaine in liver/kidney disease; using plain lidocaine or articaine infiltration in coagulopathy; selecting chloroprocaine in true amide allergy. The reviewed studies strongly support the use of mepivacaine, articaine, and lidocaine as the most favorable agents across a range of systemic conditions.

This review is limited by the heterogeneity of the available literature and the lack of randomized controlled trials (RCTs), which restricts the ability to extract rigorous evidence regarding the selection of local anesthetics for dental treatment in medically compromised patients. While this comprehensive review provides a framework for dental professionals in selecting the safest anesthetic based on the best currently available evidence, there remains a need for high-quality RCTs focusing on patients with multiple comorbidities, the long-term safety of emerging formulations such as buffered, low-epinephrine, and liposomal agents, the development of personalized anesthetic protocols using artificial intelligence or clinical risk calculators, and broader safety assessments of ester anesthetics in allergic or pediatric populations.

Conclusion

The selection of local anesthetics for dental treatment in medically compromised patients should be guided by their medical status. Mepivacaine and prilocaine are suitable for cardiovascular patients, articaine for hepatic/renal conditions, and lidocaine for use during pregnancy. Chloroprocaine is an important option for patients with amide allergies. Personalized care based on systemic risk ensures safer and more effective dental management.

Author contributions statement

G.G. and M.Z.N. conceptualized the review, conducted the literature search, contributed substantially to data analysis and interpretation, and were primarily responsible for drafting and critically revising the manuscript. E.O. contributed to the thematic organization of findings, provided clinical insight into anesthetics for dental treatment in medically compromised patients, and reviewed the manuscript for important intellectual content and clinical relevance. H.A.A. assisted in synthesizing data, contributed to the interpretation of evidence across the screened studies, and helped revise the manuscript for clarity, consistency, and scientific rigor. All authors reviewed and approved the final version of the manuscript and agreed to be accountable for its contents.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.