CRITICAL LIMITS FOR THERAPEUTIC DRUG LEVELS
Critical Limits for Therapeutic Drug Levels Elina Kuang, Yasmeen Ibrahim, Kyle Cheng, and Gerald J. Kost, MD, PhD, MS, FADLM
A
critical limit is an upper or lower numerical threshold of a diagnostic test that, when exceeded or fallen below, indicates a potentially life-threatening condition and requires immediate clinician notification. For drugs, critical limits represent concentrations associated with serious toxicity or loss of therapeutic effect. A critical value is defined as a qualitative result that also warrants urgent clinician notification. Critical values for drugs are commonly reported using qualitative notification phrases, indicating detection of a substance. An analyte is defined as a substance measured in a laboratory test.1 The concept of critical values for drug levels was originally developed by the late Daniel M. Baer, MD, and first published in the April 1982 issue of MLO. Tables 1-4 represent the first large- scale national analysis of critical limits for drugs, demonstrating variability between hospitals and offering a reference point for hospitals
to compare their practices. It consolidates and compares current practices to consensus recommendations for critical decision thresholds. Critical limits were collected by Kuang et al from 417 hospitals from all 50 U.S. states and Washington D.C. 411 of those kept drug critical limits lists. The research was originally published in the journal Clinical Pharmacology & Therapeutics (CPT). The generally accepted definition for trough concentrations is defined as the measured drug concentration obtained immediately before the next scheduled dose. Peak is defined as the measured drug concentration obtained at a specified time after drug administration. Random is defined as a drug concentration measured at an unspecified time relative to dosing.1 REFERENCE 1. Kuang E, Ibrahim Y, Cheng K, Kost GJ. Drug critical limits for urgent physician notification. Clin Pharmacol Ther. Published online 2026. doi:10.1002/cpt.70277.
Table 1. Cardiopulmonary critical limits1
Measurand
Listing frequency % (n = 411)
Units
Median (range)
25th Percentile
75th Percentile
Percent differencea
Quartile coefficient of dispersionb
99.8
ng/mL
2.5 (2–4)
2.4
2.6
100
4
nmol/L
3.2 (2.6–5.1)
3.1
3.3 80
14
60
8
33
14
100
9
300
14
100
0
0
0
400
11
Antiarrhythmic Digoxin
Lidocaine
Procainamide
28.5
15.8
Procainamide + N-Acetyl Procainamide (NAPA)
14.1
Quinidine
13.9
N-Acetyl Procainamide (NAPA)
10.2
Amiodarone +
2.9
Desethylamiodarone Flecainide
2.9
μg/mL
6 (5–9)
6
8
μmol/L
25.6 (21.3–38.4)
25.6
34.1
μg/mL
12 (10–16)
12
16
μmol/L
51 (42.5–68)
51
68
μg/mL
40 (30–40)
30
40
μmol/L
–
–
–
μg/mL
6 (5–10)
5
6
μmol/L
18.5 (15.4–30.8)
15.4
18.5
μg/mL
40 (10–40)
30
40
μmol/L
144.2 (36.1–144.2)
108.2
144.2
μg/mL
2.5 (2.5–5)
2.5
2.5
μmol/L
–
–
–
mg/L
1 (1–1)
1
1
μmol/L
2.4 (2.4–2.4)
2.4
2.4
μg/mL
20.1 (15–75)
20
25
μmol/L
111.6 (83.3–416.25)
111
138.8
Bronchodilator Theophylline
72.3
SI conversion factors are provided in Supplementary Table S3 of the original Clinical Pharmacology and Therapeutics article. n = number of hospitals. Percent difference = [(maximum − minimum)/(minimum)] × 100. bQuartile coefficient of dispersion (QCD) = [(Q3 − Q1)/(Q3 + Q1)] × 100.
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