β-Blocker Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management

Figures & data

TABLE 1. Properties of β-adrenergic receptor blockers.

	Cardioselectivity	Lipophilicity	Protein binding	ISA	Membrane stabilizing effect	Time to peak plasma concentration (hr)	Elimination t½ (hr)
Acebutolol	β1	Low	25%	Yes	Yes	2–4	2–4
Atenolol	β1	Low	< 5%	No	No	2–4	5–8
Carvedolol	β1/β2, α1	High	95–98%	No	Yes	1–2	6–10
Labetalol	β1/β2, α1	Low-moderate	50%	No	No	1–2	8
Metoprolol	β1	Moderate	10%	No	No	1.5–2	3–4
Nadolol	β1/β2	Low	30%	No	No	3–4	10–20
Propranolol	β1/β2	High	90%	No	Yes	1–2	3–5
Sotalol	β1/β2	Low	0%	No	No	2–4	10–20
Timolol	β1/β2	Low-moderate	< 10%	No	No	1–2	2–4

^*Intrinsic sympathomimetic activity.

TABLE 2. Summary of pediatric β-blockers guidelines obtained from 17 US poison control centers.

Drug	Hospital referral threshold for children	# of Poison Centers
Atenolol	Any amount	2
	> 1 mg/kg	1
	> 1.4 mg/kg	1
	> 2 mg/kg	5
	> 3 mg/kg	1
	> 4 mg/kg	1
	> 5 mg/kg	1
	1 tablet	1
	> lowest single therapeutic dose	1
	≥ daily dose	2
	> 2 × prescribed dose or maximum therapeutic dose, (whichever is larger)	1
Metoprolol	Any amount	2
	> 2 mg/kg (doesn't specify form)	2
	> 2 mg/kg IR or > 5 mg/kg SR	1
	> 3 mg/kg (doesn't specify form)	1
	> 4 mg/kg (doesn't specify form)	1
	> 5 mg/kg IR or > 10 mg/kg SR	1
	> 8 mg/kg (doesn't specify form)	1
	> lowest single therapeutic dose	1
	> maximum recommended dose	1
	≥ daily dose	3
	> 2 × prescribed dose or maximum therapeutic dose (whichever is larger)	1
Propranolol	Any amount	2
	> 2 mg/kg (doesn't specify form)	2
	> 2 mg/kg IR or > 5 mg/.kg SR	1
	> 4 mg/kg IR or > 12.5 mg/kg SR	1
	> 3 mg/kg (doesn't specify form)	1
	> 4 mg/kg (doesn't specify form)	1
	> 6 mg/kg (doesn't specify form)	1
	> 8 mg/kg (doesn't specify form)	1
	1 tablet	1
	> lowest single therapeutic dose	1
	> daily dose	1
	> maximum recommended dose	2
	> 2 × prescribed dose or maximum therapeutic dose, (whichever is larger)	1

IR—immediate release; SR—sustained release.

TABLE 3. Therapeutic doses of β-blockers in adults and children over 6 years of age.

	Usual lowest single therapeutic dose	Usual maximum single therapeutic dose	Usual maximum daily dose	Dosing frequency	Oral dosage forms
Acebutolol	Adult: 100–200 mg	600 mg	1200 mg	qd-tid	IR: 200, 400 mg caps
	Ped: 10 mg.kg	12 mg/kg	12 mg/kg
Atenolol	Adult: 25–50 mg	200 mg	200 mg	qd	IR: 25, 50 100 mg tabs
	Ped: 1–2 mg/kg	2 mg/kg	2 mg/kg
Carvedolol	Adult: 3.125–6.25 mg	50 mg	100 mg	bid	IR: 3.125, 6.25, 12.5, 25 mg tabs
	Ped: 0.08 mg/kg	0.5 mg/kg	1.0 mg/kg
Labetalol	Adult: 100–400 mg	400 mg	800 mg	bid	IR: 100, 200, 300 mg tabs
	Ped: 2 mg/kg	20 mg/kg	40 mg/kg
Metoprolol	Adult: 100 mg SR; 100–200 mg	450 mg	IR: 450 mg SR: 400 mg	tid-qid	IR:50, 100 mg tabs SR: 50, 100, 200 mg tabs
	Ped: 0.5–2.5 mg/kg	2.5 mg/kg SR: 5 mg/kg	5 mg/kg
Nadolol	Adult: 40–80 mg	320 mg	320 mg	qd	IR: 20, 40, 80, 120, 160 tabs
	Ped: 0.5–1 mg/kg	2.5 mg/kg	2.5 mg/kg
Propranolol	Adult: 10–240 mg LA, SR: 80–160 mg	240 mg	640 mg	bid-qid	IR: 10, 20, 40, 60, 80, 90, mg tabs SR: 60, 80, 120, 160 mg caps Oral solution: 4, 8, 80 mg/mL
	Ped: 0.25–1 mg/kg	4mg/kg SR 5 mg/kg	16 mg/kg
Sotalol	Adult: 80 mg	160 mg	480 mg	bid-qid	IR: 80, 120, 160, 240 mg tabs
	Ped: 1–2 mg/kg	4 mg/kg	8 mg/kg
Timolol	Adult: 1 gtt 0.5% 10 mg	30 mg	60 mg	bid	Solution 0.25%, 0.5% IR: 5, 10, 20 mg tabs
	Ped: No safe dose	No safe dose	No safe dose

IR—immediate release; SR—sustained release.

From Refs. 10-17.

TABLE 4. Maximum recommended single therapeutic dose, lowest reported toxic dose, and longest reported delay in onset of toxicity for β-blockers.

Drug	Usual maximum recommended single therapeutic dose	Lowest reported toxic oral dose	Longest reported delay in onset of toxicity
Acebutolol	Adult: 600 mg	Adult: 4000 mg [19]	N/A
	Child: 12 mg/kg	Child: N/A
Atenolol	Adult: 200 mg	Adult: 500 mg [20]	2.5 hr [21]
	Child: 2 mg/kg	Child: 5.3 mg/kg [4]
Carvedolol	Adult: 50 mg	Adult: 1050 mg [33]
	Child: 0.5 mg/kg	Child: no case reports
Labetalol	Adult: 400 mg	Adult: 6000 mg [22]	< 3 hr [22]
	Child: 20 mg/kg	Child: no case reports
Metoprolol	Adult: 450 mg (IR), 400 mg (SR)	Adult: 7500 mg [23]	3 hr [43]
	Child: 2.5 mg/kg (IR),5 mg/kg (SR)	Child: no case reports
Nadolol	Adult: 320 mg	Adult: no case reports	N/A
	Child: 2.5 mg/kg	Child: no case reports
Propranolol	Adult: 240 mg	Adult: 800 mg [27]	< 6 hr (IR) [26] 7 hr (SR) [23]
	Child: 4 mg/kg (IR), 5 mg/kg (SR)	Child: 5 mg/kg (IR), 12 mg/kg (SR) [4]
Sotalol	Adult: 160 mg	Adult: 560 mg [24]	N/A
	Child: 4 mg/kg	Child: no case reports
Timolol	Adult: 30 mg tabs	Adult: no case reports	N/A
	Child: no safe dose	Child: no dosing data

IR—immediate release; SR—sustained release.

TABLE 5. Recommended referral to an emergency department based on dose.

Drug	Adults	Children
Acebutolol	> 600 mg	> 12 mg/kg
Atenolol	> 200 mg	> 2 mg/kg
Carvedolol	> 50 mg	> 0.5 mg/kg
Labetalol	> 400 mg	> 20 mg/kg
Metoprolol	> 450 mg (IR)	> 2.5 mg/kg (IR)
	> 400 mg (SR)	> 5 mg/kg (SR)
Nadolol	> 320 mg	> 2.5 mg/kg
Propranolol	> 240 mg	> 4 mg/kg (IR)
		> 5 mg/kg (SR)
Sotalol	> 160 mg	> 4 mg/kg
Timolol	> 30 mg tabs	No safe dose

IR—immediate release; SR—sustained release.

^*Assumes unintentional ingestion in an asymptomatic patient without underlying severe medical condition or concomitant calcium channel blocker ingestion.

Table

Grade of recommendation	Level of evidence	Description of study design
A	1a	Systematic review (with homogeneity) of randomized clinical trials
	1b	Individual randomized clinical trials (with narrow confidence interval)
	1c	All or none (all patients died before the drug became available, but some now survive on it; or when some patients died before the drug became available, but none now die on it.)
B	2a	Systematic review (with homogeneity) of cohort studies
	2b	Individual cohort study (including low quality randomized clinical trial)
	2c	“Outcomes” research
	3a	Systemic review (with homogeneity) of case-control studies
	3b	Individual case-control study
C	4	Case series, single case reports (and poor quality cohort and case control studies)
D	5	Expert opinion without explicit critical appraisal or based on physiology or bench research
Z	6	Abstracts

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