What are the potential side effects and considerations for using epinephrine (adrenaline) for anesthesia in patients with a history of cardiovascular disease, epilepsy, or liver disease?

Side Effects of Epinephrine for Anesthesia

Epinephrine-containing local anesthetics are safe for use in patients with controlled cardiovascular disease, epilepsy, and liver disease, with the primary concerns being cardiovascular effects (tachycardia, hypertension, arrhythmias) and rare injection site complications, rather than absolute contraindications based on these comorbidities. 1, 2, 3

Cardiovascular Side Effects

Common Hemodynamic Changes

• Tachycardia and hypertension are the most frequent cardiovascular effects, with systolic blood pressure increasing approximately 4% and heart rate increasing 5% after standard dental doses 4
• Rate-pressure product increases by approximately 10%, reflecting increased myocardial oxygen demand 4
• Cardiac index increases by 14% while total peripheral resistance decreases by 10%, representing the β-adrenergic vasodilatory effects 4

Serious Cardiovascular Complications

• Arrhythmias including ventricular fibrillation can occur, particularly in patients with underlying organic heart disease or those receiving drugs that sensitize the heart to arrhythmias 3
• Angina pectoris may be precipitated or aggravated in patients with coronary artery disease 3
• Cerebral hemorrhage from rapid blood pressure rises, particularly in elderly patients with cardiovascular disease 3
• Stress cardiomyopathy has been reported in observational studies 3

Neurological and Psychiatric Side Effects

Common Symptoms

• Anxiety, apprehensiveness, and restlessness occur frequently with therapeutic doses 3
• Tremor, weakness, and dizziness are common neurological manifestations 3
• Headache is frequently reported 3

Specific Neurological Concerns

• Patients with Parkinson's disease may experience psychomotor agitation or temporary worsening of symptoms 3
• Patients with epilepsy can safely receive epinephrine-containing anesthetics, as the primary anesthetic concern relates to the seizure-modulating properties of the anesthetic agents themselves rather than epinephrine 5

Injection Site Complications

Tissue Necrosis and Ischemia

• Accidental injection into digits, hands, or feet may result in loss of blood flow and tissue necrosis due to epinephrine's strong vasoconstrictive effects 3
• Repeated injections at the same site can cause vasoconstriction-induced tissue necrosis 3
• Injection into the buttock is contraindicated and associated with Clostridial infections (gas gangrene) 3

Infectious Complications

• Rare cases of necrotizing fasciitis and myonecrosis caused by Clostridia have been reported at injection sites 3
• Clostridium spores can be present on skin and introduced into deep tissue; alcohol cleansing does not kill these spores 3

Metabolic and Endocrine Effects

• Diabetic patients experience transient increases in blood sugar 3
• Patients with hyperthyroidism require cautious administration due to enhanced sensitivity to adrenergic effects 3
• Patients with pheochromocytoma require caution, though this is not an absolute contraindication in life-threatening situations 3

Special Population Considerations

Patients with Cardiovascular Disease

• Controlled hypertension or stable cardiovascular disease does not contraindicate epinephrine use when blood pressure is <180/110 mmHg 1, 2
• Small amounts of epinephrine (1:80,000 to 1:200,000 concentrations) in volumes of 1.8-3.6 mL have been demonstrated safe in dental settings 1
• No significant differences in hemodynamic responses were found related to cardiac functional capacity (NYHA class I-III) in research studies 4
• Myocardial ischemic changes were not recorded in patients with known ischemic heart disease receiving 10 mL of 2% lidocaine with 1:100,000 epinephrine 6

Patients with Liver Disease

• Liver disease is not specifically contraindicated in the FDA labeling or major guidelines for epinephrine use in anesthesia 3
• Standard precautions apply regarding drug metabolism and clearance, but epinephrine itself is primarily metabolized by catechol-O-methyltransferase and monoamine oxidase, which are widely distributed 3

Allergic Reactions

• Sodium bisulfite preservative in epinephrine formulations may cause mild to severe allergic reactions including anaphylaxis in sulfite-sensitive individuals 3
• The presence of bisulfite should not preclude use in life-threatening situations, as alternatives may not be satisfactory 3

Critical Safety Precautions

Dosing and Administration

• Maximum safe dose of lidocaine with epinephrine is 7.0 mg/kg (medical) or 4.4 mg/kg (dental) 1
• Always aspirate before injection and inject slowly in incremental doses while monitoring for early signs of toxicity 2, 7
• Epinephrine remains the most widely used intravascular marker, though reliability is impaired with β-blockade, anesthesia, advanced age, and active labor 7

Monitoring Requirements

• Monitor blood pressure and heart rate, especially in the first 5-10 minutes after injection 2
• Defer elective procedures if systolic BP ≥180 mmHg or diastolic BP ≥110 mmHg until hypertension is optimized 2
• Calculate maximum allowable dose based on patient weight before starting 2

Emergency Preparedness

• Have 20% intravenous lipid emulsion (Intralipid) immediately available as the primary antidote for local anesthetic systemic toxicity 2
• For severe hypertension from epinephrine, have alpha-blockers (phentolamine) available, NOT beta-blockers alone 2
• Avoid isolated beta-blockade for severe hypertension (>220/120 mmHg), which can precipitate pulmonary edema and cardiac arrest; use alpha-blockade first or combined alpha-beta blockade (labetalol) 2

Common Pitfalls to Avoid

• Do not withhold epinephrine based on outdated concerns about "end arteries" in digits, ears, nose, hands, and feet—extensive research has refuted these concerns 2
• Avoid using lidocaine with epinephrine within 4 hours of other local anesthetic interventions to prevent cumulative toxicity 2
• Do not exceed maximum dosing limits even in small procedures 2
• Some authors recommend avoiding epinephrine in local anesthesia for sickle cell disease patients, though this remains controversial 8
• Safe limits with halothane anesthesia are 10 mL of 1:100,000 epinephrine in 10 minutes and not more than 30 mL per hour, excluding patients with cardiac disease, hypertension, or those taking MAO inhibitors 9