A journal article analysis ("journal club") I completed during an internship/Advanced Pharmacy Practice Experience (APPE) in medication safety at a hospital.

1. Paul Pasco, PHCY 4522: Medication Safety APPE, 03/21/2022
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Journal Article Analysis
Background
and
overview
Title: Medication Errors in Overweight and Obese Pediatric Patients: A Narrative Review
Author(s): Procaccini D, Kim JM, Lobner K, Rowcliffe M, Mollenkopf N
Institution: Not applicable. Meta-analysis of all relevant, available literature.
Journal: The Joint Commission Journal on Quality and Patient Safety
Funding: No source of funding identified.
Journal citation: Procaccini D, Kim JM, Lobner K, Rowcliffe M, Mollenkopf N. Medication Errors in Overweight
and Obese Pediatric Patients: A Narrative Review. The Joint Commission Journal on Quality and Patient
Safety. 2022;48(3):154-164. doi:10.1016/j.jcjq.2021.12.005.
Rationale: The rationale of this meta-analysis is to evaluate all available literature on the incidence and types
of medication errors in overweight and obese children.
Clinical Question (PICO): Are overweight and obese children at increased risk for medication errors
compared to non-overweight, non-obese children?
Methods
Primary Objective: Identify the incidence and types of medication errors overweight and obese children
experience relative to healthy weight children.
Design: This meta-analysis included all prospective studies, retrospective studies, and oral abstracts that have
reported medication errors in obese or pediatric patients ≤ 18 years with any intervention and any outcome.
Sources used were limited to MEDLINE, Embase, and Scopus databases through December 12, 2020 and
from any date prior without restriction. Primary keywords for literature searches included “overweight,” “obese,”
“pediatric,” “error,” and “medication.” Two reviewers independently evaluated each study and its methodology
with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Two of the
studies included a comparison in medication errors between obese and non-obese children. The other three
lacked comparators. Drug classes with identified dosing errors in these studies included antimicrobials,
anesthetics, and acetaminophen.
Population:
o The initial pool of studies was 1,016, but after exclusion criteria, this was reduced to 5.
▪ 400 duplicates were removed.
▪ 470 were irrelevant (pertained to adults).
▪ 141 were removed due to exclusion criteria.
• Sample Size: Consisted of 5 studies with 13 to 10,498 patients each.
o Sample sizes of 13, 200, 839, and 10,498, respectively.
o One study does not have an identified sample size because it did not involve real patients.
• Randomization: None of the studies were randomized.
• Demographics:
o Children from 1 month to ≤ 18 years.
o Three of the studies included pediatric patients ≥ 12 years.
o The remaining two studies only addressed patients ≤ 12 years.
• Inclusion: Inclusion criteria consisted of age ≤ 18 years for all studies involving overweight or obesity in
the context of medication errors.
• Exclusion: There were 7 exclusion criteria:
o Age > 18 years.
o Wrong study design, outcomes, or population.
o Not in English.
o Full text unavailable.
o Inadequate description.
• Dropouts: Not identified.
Findings/Results:
• Miller, et al. identified the frequency of dosing errors of analgesics and antimicrobials (N = 839).
o In overweight patients vs. controls, the overall mean error rate per admission was significantly
higher (0.4 ± 0.6 vs. 0.3 ± 0.6, p = 0.03).
o In overweight patients vs. controls, underdosing errors occurred more frequently than
overdosing errors (0.3 ± 0.6 vs. 0.2 ± 0.5, p = 0.01).
o In overweight patients vs. controls, there was a significantly higher mean overdose error rate
(0.06 ± 0.2 vs. 0.01 ± 0.1, p = 0.008) and underdose error rate (0.13 ± 0.4 vs. 0.07 ± 0.3, p =
0.049) of antimicrobials.
o In overweight patients vs. controls, there was a significantly lower analgesic overdose error
rate (0.01 ± 0.3 vs. 0.06 ± 0.2, p = 0.0032).

2. Paul Pasco, PHCY 4522: Medication Safety APPE, 03/21/2022
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Results o Overweight children had significantly higher odds of receiving underdoses of succinylcholine
and neostigmine.
o Overweight children were 3.5 times more likely to have received an overdose of morphine.
o Overweight children are nearly 70% less likely to have received an underdose of morphine.
o Authors recommend morphine be dosed according to IBW.
o 29.4% of patients evaluated were overweight or obese.
• Gade, et al. identified dosing errors of gentamicin, acetaminophen, and morphine (N = 200).
o Six dosing errors identified (error rate of ~1%).
o Guidelines for dosing in overweight and obese pediatric patients not available at the time of
prescribing.
• Dosing strategies included weight-based vs. flat-fixed (e.g., dosing without correction for
BSA or another pharmacological dosing parameter, such as eGFR).
o Evaluated gentamicin dosing via TBW (vs. IBW), excessive weight-based dosing of
acetaminophen, and underdosing of flat-fixed morphine based on pediatric weight-based
recommendations.
• Kannan, et al. identified pervasive errors in the dosing of six medications with narrow therapeutic
indices and high risks for toxicity, which carry suggestions to use IBW or ABW: acyclovir,
aminophylline, gentamicin, morphine, acetaminophen, and phenytoin (N = 13).
o Two methods were used to evaluate dosing errors.
1) A six-question case scenario for the specified medications was administered to seven
pediatricians (ranging from first-year residents to consultants).
2) Analysis of prescriptions for the specified medications in 13 real patients in a general
medicine ward over four weeks.
o Out of the 42 questions posed (6 questions for seven participants), 0% were answered
correctly.
o Out of the 13 patients who were prescribed the specified medications, 0% were dosed correctly.
• The minimum and average daily drug overdoses during the four-week period were
111% and 128%.
• The maximum overdose reported was 149% for acetaminophen prescribed in an 11-
year-old girl.
• Eyers, et al. reviewed dosing for acetaminophen from the 2011–2012 age-based guidelines by the
British National Formulary for Children (BNFC).
o Evaluated single and cumulative weight-based dosing for acetaminophen.
o Reviewed children of 1 month to 12 years in the 9th, 50th, and 91st (i.e., overweight or obese)
percentiles for weight and gender per established UK population growth charts.
o For children of all ages at the 91st percentile for weight, doses of acetaminophen were 33% to
50% below recommended single and cumulative daily doses when given the lowest dose
specified in the age range.
Critique
Data Analysis:
• Strengths:
o With the paucity of research in this area to date, this meta-analysis illuminates important questions
for further analysis (e.g., evaluation of causality between overweight or obesity and medication
errors, outcome measures associated with medication errors, such as increased readmission rates
secondary to errors).
o All relevant research identified to date, though limited, was reviewed during the meta-analysis.
o This article highlights the “blind spots” of many providers with dosing many ubiquitous and/or
narrow therapeutic index drugs in these populations. Even a pervasive drug like acetaminophen
has shown significant opportunity for improvement. This represents a tremendous opportunity for
provider education and collaboration with qualified clinical pharmacists.
• Limitations:
o Four of the five studies analyzed were retrospective, which reduced their significance per GRADE
criteria. Retrospective studies have several inherent limitations, including disallowing identification
of causality and the promotion of selection and reporting biases.
o The fifth study was prospective but lacked a robust sample size (N = 13), a comparator group, and
was brief (only 4 weeks).
o Most studies lacked subgroup analyses. This disallows other conclusions based on different
demographic factors (e.g., race/ethnicity).

3. Paul Pasco, PHCY 4522: Medication Safety APPE, 03/21/2022
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o Most studies were performed outside of the USA, which may lend itself to different definitions of
overweight and obesity, different dosing recommendations (e.g., by foreign manufacturers and/or
tertiary references), etc.
o In the study that administered an objective assessment to evaluate providers’ competency, the
training background was only provided in general terms (i.e., pediatric first-year residents to
consultants) and a description of the questions used was not provided.
o None of these studies identified the clinical significance of the dosing errors on patient
outcomes.
• Internal Validity:
o This meta-analysis did not identify causal relationships between variables due to the design of
the included studies (80% retrospective, subject to selection and reporting biases).
• External Validity:
o The external validity of these results is very limited.
o The participants were almost exclusively obtained through retrospective chart review and therefore
may hold significant selection and reporting biases.
o The populations studied are not representative of the general populace (only a subset). Anyone
over the age of 18 is not represented by any of the included results.
• Opinion on Clinical Relevance:
o The article highlights an increased risk for medication errors in overweight or obese children.
These populations are not routinely seen by all practitioners (e.g., many seen by dedicated
pediatricians, pediatric EDs, pediatric hospitals). Clearer guidance on appropriate dosing in these
populations would add value to many institutions but not all.
o Due to a lack of outcome measures, despite a medication error occurring, the clinical
significance remains unknown. For example, if there is a consistent 5% overdose in
acetaminophen in the study populations, is there an increase in readmissions? The included
studies do not address this.
Authors’ Conclusions: There is severely limited evidence for how to prevent medication errors in overweight
and obese children. Based on these data, it appears that overweight and obese children are at increased risk
for medication errors. However, due to a lack of outcome measures, the clinical significance of such errors is
unknown.
Recommendations:
• Since obesity is a pervasive issue internationally, a detailed explanation of dosing strategies in these
populations is critical.
• Tertiary sources should be updated to include specific dosing strategies for these populations for all
drugs with available PK/PD data.
• Healthcare providers should endeavor to consult with qualified clinical pharmacists for dosing
recommendations in these populations due to the high propensity for errors.
• Healthcare organizations and technology vendors should brainstorm and implement harm reduction
strategies throughout the medication use process to prevent errors in these populations. Further,
studies on these strategies and their ability to reduce medication errors in these populations should be
conducted.