Metoprolol Massive Overdose – Evidence‑Based Management

Pharmacokinetics & Toxicokinetic Expectations

The volume of distribution of metoprolol is approximately 5.5 L/kg (≈ 385 L in a 70‑kg adult), indicating moderate tissue distribution and limiting the usefulness of extracorporeal removal methods. (Critical Care) 4
Metoprolol is low‑protein bound (≈ 12 %), leaving a large free fraction available for toxic effects. (Critical Care) 4
In therapeutic dosing the drug has a half‑life of 3–4 h with first‑order elimination, whereas massive overdose produces prolonged, saturable (zero‑order) elimination, extending the half‑life to > 20 h initially. (Critical Care) 4
The extended‑release (Betaloc ZOK) formulation absorbs over 12–24 h, so peak plasma concentrations may be delayed. (Critical Care) 4
Cardiovascular symptoms usually appear within 2 h but can be delayed up to 8 h with sustained‑release tablets; peak toxicity often occurs 6–12 h after ingestion. (Critical Care, Critical Care) [4][5]

Severe β‑blocker poisoning produces life‑threatening hypotension due to profound bradycardia and reduced myocardial contractility, frequently refractory to standard vasopressor therapy. (American Heart Association) [1][2]3
Bradycardia results from direct β1‑adrenergic blockade at the sinoatrial and atrioventricular nodes. (American Heart Association, Critical Care) [1][4]
Mechanisms of hypotension include:
- Cardiogenic shock from myocardial depression,
- Reduced cardiac output secondary to severe bradycardia,
- Loss of β1‑selectivity at toxic doses causing additional β2 blockade. (American Heart Association, Critical Care) [1][2]4
Central nervous system depression can occur because metoprolol is moderately lipophilic and crosses the blood‑brain barrier. (Critical Care) 4
Hypoglycemia is a recognized risk; glucose levels must be monitored and dextrose administered as needed. (American Heart Association) [1][3]

Vasopressor support (norepinephrine or epinephrine) should be initiated immediately for hypotension; high doses are often required due to partial resistance. (American Heart Association) [1][2]3
High‑dose insulin euglycemia therapy (HIET) is recommended for hypotension refractory to vasopressors; it improves myocardial inotropy and is associated with fewer vasoconstrictive complications. Typical regimen: 1 U/kg bolus followed by 1–10 U/kg/h infusion with dextrose to maintain euglycemia. (Class I, LOE B‑NR) (American Heart Association, Critical Care) [1][2][3][5]

Glucagon (5–10 mg IV bolus, then 2–10 mg/h infusion) increases cardiac contractility independent of β‑receptors; vomiting is a common adverse effect. (American Heart Association, Critical Care) [1][2][3][5]
Veno‑arterial ECMO is reasonable for refractory cardiogenic shock when maximal pharmacologic support fails; early consultation is advised. (American Heart Association) [1][2]3

Atropine (0.5–1 mg IV, repeat as needed) may be attempted for bradycardia but is often ineffective in severe β‑blocker toxicity. (American Heart Association) [1][2]3
Temporary cardiac pacing (initially transcutaneous, then transvenous if needed) may be considered, though capture can be difficult due to myocardial depression. (American Heart Association, Critical Care) [1][3]5

Intravenous lipid emulsion (ILE) is not recommended for life‑threatening β‑blocker poisoning; the 2023 AHA guidelines explicitly advise against its use. (Class III, LOE C‑LD) (American Heart Association) [1][2]3

Hemodialysis is ineffective for metoprolol overdose because of its high volume of distribution (5.5 L/kg) and moderate lipophilicity. (Critical Care) 4

Continuous ECG for bradyarrhythmias and conduction disturbances. (Critical Care) 4
Arterial line for beat‑to‑beat blood pressure monitoring; consider pulmonary artery catheter for cardiac index if needed. (Critical Care) 4
Hourly blood glucose during HIET, with prompt treatment of hypoglycemia. (American Heart Association) 1
Serum potassium monitoring to detect hyper‑ or hypokalemia. (Critical Care) 4
Observation period: at least 12 h for asymptomatic patients (due to extended‑release absorption) and 24–48 h ICU monitoring for symptomatic individuals. (Critical Care) 4

Favorable: single‑agent metoprolol exposure and early aggressive treatment with vasopressors + HIET; availability of ECMO support improves survival. (Critical Care, American Heart Association) [4][1]3
Unfavorable: co‑ingestion of calcium‑channel blockers or other cardioactive drugs, development of cardiac arrest, and prolonged hypotension leading to multi‑organ failure. (Critical Care) 4