High-alert medication errors reported in a critical care unit in Spain: an observational study
Maria-Consuelo Pintado-Delgado1
, Isabel-Maria Sánchez-Navarro2, Miguel Serrano-Garcia2, Gemma Baldominos-Utrilla2
Contributions: (I) Conception and design: MC Pintado-Delgado, M Serrano-Garcia, G Baldominos-Utrilla; (II) Administrative support: IM Sánchez-Navarro, MC Pintado-Delgado, G Baldominos-Utrilla; (III) Provision of study materials or patients: MC Pintado-Delgado, M Serrano-Garcia, G Baldominos-Utrilla; (IV) Collection and assembly of data: MC Pintado-Delgado, IM Sánchez-Navarro, MC Pintado-Delgado; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Background: High-alert medications (HAMs) are drugs that have an increased risk of causing significant patient harm when they are used erroneously. HAM use in intensive care unit (ICU) is high, where the incidence of medication errors is estimated at 1.2 to 96.7 medication errors (ME) per 1,000 patient-day. The purpose of this study is to describe the voluntarily reported ME related to HAMs in an adult ICU.
Methods: In this retrospective observational study conducted in Spain, we reviewed all the ICU ME related to HAMs reported to intranet-accessible, anonymous adverse event-reporting program by healthcare professionals over 36 months.
Results: Of the 268 medication errors reported, 102 (38.0%) were related to HAMs. Insulin (19.6%), followed by adrenergic agonist (15.7%), were the most frequent drug classes associated with medication errors. Prescription errors (54.0%) were the most frequent type of error, mainly related to the use of verbal orders that were not prescribed. Most of the reported medication errors (63.7%) did not result in harm to the patient. Alterations in plasma glucose levels were the most frequent type of harm. All reported damages were transient and resolved with treatment, but all of them prolonged the stay in ICU.
Conclusions: ME related to HAMs in ICU are frequent, up to 38% of all the ME notified. In our study, most of them were due to prescription errors and related to insulin and adrenergic agonist. Although in most cases they are not related to permanent damage or death, their occurrence is associated with an increase in the length of stay in the ICU.
Keywords: Intensive care; medication errors (ME); high-risk medications; patient safety; medication safety
Received: 19 July 2024; Accepted: 09 October 2025; Published online: 02 December 2025.
doi: 10.21037/jeccm-24-104
Highlight box
Key findings
• Up to 38% of all the medication errors notified in intensive care unit (ICU) are related to high-alert medications (HAMs).
• Only 36.3% of them results in harm to the patient. However, when this occurred, it prolonged the stay in the ICU.
What is known and what is new?
• Little is known about the harm caused by medication errors related to HAMs in the ICU.
• We describe the incidence of reported medication errors related to high-risk drugs in ICU, their type and the resulting harm to patients.
What is the implication, and what should change now?
• Measures should be taken to improve or assist in the prescription, administration and identification of HAMs in the ICU.
Introduction
Medication errors comprise any avoidable adverse event that occurs during the medication management cycle (1).
In the intensive care unit (ICU), patients are prescribed twice as many medications as those admitted to the general wards. This, combined with the complexity of patient pathology and the dynamic nature of the ICU environment, significantly increases the risk of medication errors (ME) (2-5). Also, critical patients in the ICU are more vulnerable to ME due to the highly frequent occurrence of organ dysfunction (primarily renal and hepatic impairment) which, along with the underlying disease, alters the pharmacodynamics and pharmacokinetics of many drugs (2-5). So, it is estimated an incidence of 1.2 to 96.7 ME per 1,000 patient-days in ICU (2-5). This wide range of reported incidence is due to the different ways of collecting medical errors: direct observation, internal or external reviews by physicians or pharmacists, interviews, or verbal self-reporting.
According to the Institute for Safe Medication Practices (ISMP), a nonprofit organization dedicated to the prevention of medication errors, high-alert medications (HAMs) are drugs that have an increased risk of causing significant patient harm when they are used erroneously (6). ISMP creates and periodically updates a list of HAMs (7), many of which are commonly used in ICU settings. However, data on medication errors specifically related to HAMs in the ICU remain limited. The aim of this retrospective observational study is to describe the ME involving HAMs that were voluntarily reported in an adult ICU in Spain. We present this article in accordance with the STROBE reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-104/rc).
Methods
Study design and participants
In this retrospective observational study, we reviewed all ICU ME related to HAMs according to ISMP (6), reported by healthcare professionals to the incident communication system of patient safety without harm and medication errors of the Community of Madrid (CISEMadrid) over 36 months (from February 1, 2020, to January 31, 2023).
CISEMadrid is an anonymous, intranet-based adverse event reporting program used in our hospital to voluntarily notify patient safety incidents and ME, with the aim of improving clinical safety practices.
This study was conducted in an adult 18-bed medical-surgical ICU at a level 2 university hospital in Spain, with an average annual admission rate of approximately 600 patients. The unit operates with an electronic health record system (HCIS), which includes integrated medication prescribing functionalities. However, a paper-based nursing chart is still in use, resulting in duplicate documentation of medication administration (electronic and paper-based). Medication prescriptions in the ICU utilize the hospital-wide system and database, without a dedicated ICU-specific program. The nurse-patient ratio is 1:2.
Data collection
Data collected included: the drug involved, the medication use process node (prescribing, transcribing, documenting, dispensing, preparing, administering, monitoring, systems management and control), the type of error, contributing factors, patient outcomes, and what time of day it took place (morning, evening, night shift, or on-call). Types of medication errors were classified according to the Spanish adaptation of the taxonomy of the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) (8). Classification was performed independently by a pharmacist and an ICU clinician. All variables were collected from the CISEMadrid program. All collected data are nominal and qualitative in nature; therefore, they are described using absolute frequencies (n, number) and relative frequencies (%, percentage). No further statistical analysis was performed beyond descriptive statistics. Data are located in controlled access data storage at Consejeria de Sanidad Comunidad de Madrid (https://cisemadrid.salud.madrid.org).
Ethical considerations
This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by Institutional Ethics and Clinical Trials Committee of Principe de Asturias University Hospital on May 30, 2023 (internal number: OE 41/2023) in accordance with the European and Spanish law. This study does not require informed consent from the patient, since the CISEMadrid system is an anonymous system for reporting medication errors.
Results
During the study period, 268 ME were voluntarily reported into CISEM system. Of them, 102 (38.0%) were related to HAMs.
A single medication error was involved in 97 (95.1%) cases, and two or more in 6 (5.9%). The most frequently implicated drug in medication errors was insulin (19.6%), followed by adrenergic agonist (15.7%). Errors involving insulin were primarily due to the administration of insufficient doses, which led to the development of hyperglycemia, and even reappearance of diabetic ketoacidosis in the transition from intravenous insulin treatment to subcutaneous in 4 patients; insulin dosage was increased only in 2 patients, both of whom resulted in symptomatic hypoglycemia. Table 1 shows the medication groups involved in the reported medication errors.
Table 1
| Drug class | N (%) | Drug (n) |
|---|---|---|
| Adrenergic agonists IV | 16 (15.7) | Norepinephrine: 16 |
| Anesthetic agents, general, inhaled and IV | 11 (10.8) | Propofol: 9, ketamine: 2 |
| Antiarrhythmics IV | 6 (5.9) | Amiodarone: 5, digoxin: 1 |
| Antithrombotic agents | 8 (7.8) | Enoxaparin: 5, urokinase: 2, tenecteplase: 1 |
| Epidural medications | 1 (1.0) | Levobupivacaine: 1 |
| Insulin, SC and IV | 20 (19.6) | |
| Liposomal forms of drugs | 1 (1.0) | Amphotericin: 1 |
| Magnesium sulfate injection | 1 (1.0) | |
| Moderate sedation agents | 10 (9.8) | Midazolam: 7, dexmedetomidine: 2, dipotassium clorazepate: 1 |
| Opioids, IV, oral, transdermal | 11 (10.8) | Fentanyl: 5, morphine: 3, remifentanil: 3, methadone: 2 |
| Neuromuscular blocking agents | 4 (3.9) | Cisatracurium: 3, rocuronium: 1 |
| Parenteral nutrition preparations | 2 (1.9) | |
| Potassium chloride for injection concentrate | 8 (7.8) | |
| Potassium, phosphates injection | 1 (1.0) | |
| Sterile water for injection, inhalation and irrigation in containers of 100 mL or more | 1 (1.0) |
IV, intravenous; SC, subcutaneous.
In 11 of the 102 notifications, 2 types of errors were reported, resulting in a total of 113 errors included in the final analysis. The most frequent type of medication error was related to prescription (54.0%), particularly involving verbal orders that were not formally documented. This was followed by administration errors (36.3%), mainly associated with the delivery of incorrect doses. Table 2 summarizes the main characteristics of ME involving HAMs.
Table 2
| Medication use process (n, %) | Type of error (n) |
|---|---|
| Prescribing (61, 54.0%) | Drug ordered verbally but not prescribed on chart and omitted on subsequent days’ charts: 32 |
| Incorrect dose: 10 | |
| Incorrect drug: 6 | |
| Wrong administration route: 5 | |
| Wrong patient: 3 | |
| Drug prescribed after prior verbal stop order: 2 | |
| Other: 3 | |
| Administering (41, 36.3%) | Incorrect dose: 22 |
| Prescribed drug not administered: 8 | |
| Incorrect drug: 4 | |
| Drug administered after stop order on chart: 2 | |
| Incorrect dosing interval: 1 | |
| Other: 4 | |
| Dispensing (4, 3.5%) | Incorrect drug: 2 |
| Expired medicine: 1 | |
| Not dispensed: 1 | |
| Preparing (1, 0.9%) | Labeling with erroneous medication: 1 |
| Documentation (3, 2.6%) | Duplicate record (paper and electronic) that do not match: 3 |
| Monitoring (1, 0.9%) | Lack of glycemic controls: 1 |
| Other (2, 1.8%) | Infusion pump failure: 1 |
| Drug administered without medical order (verbal or written): 1 |
HAM, high-alert medication.
Fortunately, the majority of the reported errors (63.7%) did not result in harm to the patient. As expected, alterations in plasma glucose levels were the most common adverse effect, given that insulin was the drug most frequently implicated in the reported errors (Table 3). All reported damages were transient and resolved with appropriate treatment; however, all of them prolonged the ICU stay, since they all required at least one day of observation to verify that the damage had been corrected.
Table 3
| Presence of harm | N (%) | Clinical manifestation (n) |
|---|---|---|
| Patient harm | 35 (34.3) | Symptomatic poisoning from ketamine overdose: 1 |
| Desaturation and maladaptation of mechanical ventilation: 3 | ||
| Hyperglycaemia, glycaemic decompensation: 10 | ||
| Hypoglycaemia: 4 | ||
| Pain: 4 | ||
| Asymptomatic hypokalaemia: 4 | ||
| Hypotension: 2 | ||
| Hypertension: 1 | ||
| Heart failure: 1 | ||
| Persistence of empyema: 1 | ||
| Persistent hematuria: 2 | ||
| Oversedation, delay in wake up: 1 | ||
| Non-lysis of pulmonary thrombus: 1 | ||
| No patient harm | 65 (63.7) | |
| Unknown | 2 (2.0) |
Most of the errors occurred during the day, with the morning shift (33%) followed by the afternoon shift (30%) (Figure 1).
Discussion
Despite the widespread use of HAMs in adult ICUs, there is limited literature specifically addressing medication errors associated with these drugs. To date, only one study has focused exclusively on errors related to HAMs in adult ICUs (9), although several others provide partial data on this topic (6,9).
As in previous studies of ME in ICU, we found that prescribing errors were the predominant type of error (54.0%), particularly omissions following verbal orders (52.5%). This aligns with findings from other ICU studies, where prescribing errors account for 38.7% to 70.0% of all reported medication errors, mainly due to incorrect dosages and omissions (2-4,10). We found that 38% of ME voluntarily reported cases were associated with HAMs, with insulin (19.6%) and adrenergic agonist (15.7%) being the most frequently implicated drug classes.
Benkirane et al. (5) prospectively evaluated adverse drug events across 7 adult and pediatric ICUs over 3 months, reporting an incidence rate of 11.5%, mainly due to prescribing errors. The most frequently implicated drugs included antidiabetics (insulin), anesthetics (lidocaine and bupivacaine), cardiovascular (diuretics), anti-infectives, and analgesics. In their study, Garrouste-Orgeas et al. (11) focused on insulin and anticoagulant-related errors in ICU, reporting an incidence of 567.5 medication errors/1,000 patient-days. Kane-Gill et al. (2) retrospectively analyzed 3252 medication errors voluntarily reported medication errors over 4.5 years in their hospital, of which 541 occurred in the ICU. Among these, 183 (33.8%) were related to HAMs according to the ISMP, including opioid analgesics (13.2%), coagulation modifiers (6.4%), insulin (5.9%), and electrolytes (4.6%). Prescribing errors were the most frequent. Bosma et al. (12) analyzed 354 voluntarily reported medication errors from 11 Dutch adult ICUs, finding that 123 (34%) involved HAMs. The most commonly implicated drugs were antithrombotic agents (especially low-molecular-weight heparins), opioids, insulin and tacrolimus.
In our study, none of the reported medication errors resulted in significant permanent harm or death. However, 34.3% of cases involving patient harm led to prolonged ICU stays. This may reflect a reporting bias, as incidents with clinical consequences are more likely to be notified. Previous studies have reported harm rates ranging from 0% to 12% (3,4,6) for ICU-related medication errors, although specific data on HAMs in the ICU remain scarce. Garrouste-Orgeas et al. (11) found that 95% of anticoagulant-related errors and 83% of insulin-related errors had no clinical consequence to the patient. Benkirane et al. (5) reported serious outcomes (seriousness was defined as a ME that results in death or is life threatening, or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity) in 4% of insulin-related errors, 6% of anesthetics-related errors (lidocaine and bupivacaine), and less than 1% for cardiovascular (diuretics), anticoagulant, and sedation/analgesic drugs.
A recent study by Aradhya et al. (10) in India identified 204 HAM-related errors over 6 months, with an incidence of 160.12 errors/1,000 patient-days. Prescribing errors (45.1%) and documentation errors (33.8%) were most frequent, primarily involving drugs from the alimentary tract and metabolism group, such as potassium chloride (12.94%), insulin (9.45%), and sodium chloride (5.47%).
As in previous studies (13,14) and contrary to what one might think, most errors did not occur during the night or the 24-hour shift, where fatigue and sleepiness might influence their occurrence, but rather during the day. This is probably due to the higher activity during the day, with a greater workload, the visit of doctors from other specialities and the presence of nurses and doctors in training.
The strength of this study is that it focuses on medication errors related to high-risk drugs in the ICU; it is also the only study conducted in Spain on this specific topic.
This study has several limitations. First, it was conducted in a single-center ICU, and may not be generalizable to other centers. Second, it relied on voluntarily reported errors, so the real incidence of this kind of error is not known because medication errors are always underreported (8,15) and suffer from “self-report bias” (16). Third, we did not use a standardized tool to assess clinical outcomes related to medication errors.
Conclusions
In conclusion, we found that ME involving HAMs are frequent in the ICU, accounting for up to 38% of all the ME notified. Most were related to prescribing, particularly undocumented verbal orders, and primarily involved insulin and adrenergic agonists. Although no permanent harm or fatalities were observed, errors associated with patient harm contributed to prolonged ICU stays. These findings highlight the need for targeted interventions to improve prescribing practices and reduce the incidence of HAM-related errors in critical care settings.
Acknowledgments
We wanted to thank all staff of Principe de Asturias University Hospital interested in patient safety, who report medication errors.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-104/rc
Data Sharing Statement: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-104/dss
Peer Review File: Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-104/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-24-104/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by Institutional Ethics and Clinical Trials Committee of Principe de Asturias University Hospital on May 30, 2023 (internal number: OE 41/2023) in accordance with the European and Spanish law. This study does not require informed consent from the patient, since the CISEMadrid system is an anonymous system for reporting medication errors.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- NCCMERP. About Medication Errors [updated 16 Nov 2022]. Available online: https://www.nccmerp.org/about-medication-errors
- Kane-Gill SL, Kowiatek JG, Weber RJ. A comparison of voluntarily reported medication errors in intensive care and general care units. Qual Saf Health Care 2010;19:55-9. [Crossref] [PubMed]
- Kumar M, Sahni N, Shafiq N, et al. Medication Prescription Errors in the Intensive Care Unit: Prospective Observational Study. Indian J Crit Care Med 2022;26:555-9. [Crossref] [PubMed]
- Yoon J, Yug JS, Ki DY, et al. Characterization of Medication Errors in a Medical Intensive Care Unit of a University Teaching Hospital in South Korea. J Patient Saf 2022;18:1-8. [Crossref] [PubMed]
- Benkirane RR, Abouqal R, Haimeur CC, et al. Incidence of adverse drug events and medication errors in intensive care units: a prospective multicenter study. J Patient Saf 2009;5:16-22. [Crossref] [PubMed]
- Zirpe KG, Seta B, Gholap S, et al. Incidence of Medication Error in Critical Care Unit of a Tertiary Care Hospital: Where Do We Stand? Indian J Crit Care Med 2020;24:799-803. [Crossref] [PubMed]
- ISMP-España. Lista de Medicamentos de Alto Riesgo para Hospitales [Accessed Sep 19th, 2025]. Available online: https://www.ismp-espana.org/ficheros/Medicamentos%20alto%20riesgo%20-ISMP.pdf
- Arabi YM, Al Owais SM, Al-Attas K, et al. Learning from defects using a comprehensive management system for incident reports in critical care. Anaesth Intensive Care 2016;44:210-20. [Crossref] [PubMed]
- Obuseh M, Yu D, DeLaurentis P. Detecting Unusual Intravenous Infusion Alerting Patterns with Machine Learning Algorithms. Biomed Instrum Technol 2022;56:58-70. [Crossref] [PubMed]
- Aradhya PJ, Ravi R, Chandra BJS, et al. Assessment of Medication Safety Incidents Associated with High-alert Medication Use in Intensive Care Setting: A Clinical Pharmacist Approach. Indian J Crit Care Med 2023;27:917-22. [Crossref] [PubMed]
- Garrouste-Orgeas M, Soufir L, Tabah A, et al. A multifaceted program for improving quality of care in intensive care units: IATROREF study. Crit Care Med 2012;40:468-76. [Crossref] [PubMed]
- Bosma BE, Hunfeld NGM, Roobol-Meuwese E, et al. Voluntarily reported prescribing, monitoring and medication transfer errors in intensive care units in The Netherlands. Int J Clin Pharm 2021;43:66-76. [Crossref] [PubMed]
- Macías Maroto M, Solís Carpintero L. Medication administration errors at an emergency service: knowing to decrease risk. Rev Esp Salud Publica 2018;92:e201806038.
- Summa-Sorgini C, Fernandes V, Lubchansky S, et al. Errors Associated with IV Infusions in Critical Care. Can J Hosp Pharm 2012;65:19-26. [Crossref] [PubMed]
- Thomas AN, Taylor RJ. An analysis of patient safety incidents associated with medications reported from critical care units in the North West of England between 2009 and 2012. Anaesthesia 2014;69:735-45. [Crossref] [PubMed]
- Kiekkas P, Aretha D, Karga M, et al. Self report may lead to underestimation of 'wrong dose' medication errors. Br J Clin Pharmacol 2009;68:963-4. [Crossref] [PubMed]
Cite this article as: Pintado-Delgado MC, Sánchez-Navarro IM, Serrano-Garcia M, Baldominos-Utrilla G. High-alert medication errors reported in a critical care unit in Spain: an observational study. J Emerg Crit Care Med 2025;9:29.
