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High-Alert Medication Survey Results Lead to Several Changes for 2018

Between June and July 2018, ISMP conducted a survey on high-alert medications in acute care settings to learn about possible additions or deletions before updating our longstanding list. High-alert medications are an essential component of drug therapy, but they carry a significant risk of causing serious injuries or death to patients if they are misused. Errors with these products are not necessarily more common, but the consequences of an error are often quite harmful and can even be fatal.

ISMP published its first list of “high-alert” medications in 1989 (Davis NM, Cohen MR. Today’s poisons: how to keep them from killing your patients. Nursing. 1989;19[1]:49-51). That initial list included 6 medications that are still on ISMP’s list today—intravenous (IV) lidocaine, vinCRIStine, sodium chloride for injection greater than 0.9%, morphine injection, insulin, and potassium chloride for injection concentrate. Today, our list is based upon an extensive review of errors submitted to the ISMP National Medication Errors Reporting Program (ISMP MERP), review of clinical and safety literature, input from our clinical advisory board and US safety experts, and periodic newsletter surveys. In this newsletter, we report the results of our most recent survey, compare these results to a previous survey conducted in 2014, and discuss the changes that we have made to the list. We have also included a copy of the updated ISMP List of High-Alert Medications in Acute Care Settings on page 5, of the PDF version.

2018 Survey Results

Respondent profile. ISMP extends our thanks to the 296 practitioners who completed our survey on high-alert medications in acute care settings. Most (82%) respondents were pharmacists, although nurses (10%), physicians (3%), pharmacy technicians (3%), and others (2%) also participated. Respondents were evenly split between staff-level and management-level, and nearly all (98%) worked in inpatient settings.     

Organizational lists of high-alert medications. Almost all (95%) respondents reported that their organization maintains a list of high-alert medications. However, only 64% reported that special precautions are in place to minimize and prevent errors for all of the high-alert medications on their list. Another 21% of respondents said that special precautions are in place for most of the medications on their list. However, 15% of respondents reported that there are few or no special precautions in place to minimize and prevent errors with the high-alert medications on their list.

Among respondents who reported having special precautions in place to prevent errors, most felt that they are very (20%) or mostly (55%) effective in minimizing and preventing errors with high-alert medications. One in 4 respondents thought the precautions in their organization were only somewhat (23%) or weakly (2%) effective, citing examples of how practitioners often bypass these safety precautions. A few respondents commented that they could not assess the effectiveness of precautions because they only have a voluntary medication error-reporting system in place for measurement.

When respondents were asked which 3 medications or classes of medication on their list caused the most concern with regards to medication errors, the most frequent responses were (in descending order): anticoagulants, insulin, neuromuscular blocking agents, chemotherapy, opioids, hypertonic sodium chloride injection (concentrations greater than 0.9%), adrenergic agonists, and other concentrated electrolytes. 

Medications considered high-alert. Table 1 shows the drugs on the ISMP List of High-Alert Medications in Acute Care Settings at the time of the survey, and the percent of respondents who considered these to be high-alert medications. Half or more of the 2018 respondents thought that all of the drugs on our list were high-alert except:

  • IV radiocontrast agents (34%)
  • oral hypoglycemics (29%)
Table 1. Comparison of respondents who believe these are high-alert medications, 2018 and 2014 surveys
Classes/Categories of Medications High-Alert (%)
2018 2014
chemotherapeutic agents, parenteral and oral 99 97
insulin, subcutaneous and IV 98 93
neuromuscular blocking agents 97 96
antithrombotic agents 96 92
epidural and intrathecal medications 93 94
sodium chloride for injection, greater than 0.9% 88 87
opioids, IV, oral, transdermal 83 74
moderate sedation agents, oral for children 73 70
cardioplegic solutions 73 60
dextrose, hypertonic, 20% or greater 72 64
anesthetic agents, general, inhaled and IV 71 85
moderate sedation agents, IV 69 74
adrenergic agonists, IV 69 75
parenteral nutrition 68 61
inotropic medications, IV 65 53
antiarrhythmics, IV 58 58
adrenergic antagonists, IV 57 75
sterile water for injection (inhalation/irrigation) in containers (excluding pour bottles) of 100 mL or more 52 35
liposomal forms of drugs 50 49
dialysis solutions, peritoneal/hemodialysis 50 39
radiocontrast agents, IV 34 42
hypoglycemics, oral 29 29
Specific Medications High-Alert (%)
2018 2014
insulin U-500 (special emphasis) 96 98
potassium chloride for injection concentrate 95 92
methotrexate, oral, nononcologic use 74 67
potassium phosphates injection 72 79
epoprostenol (e.g., Flolan), IV 70 64
magnesium sulfate injection 64 70
oxytocin, IV 60 61
opium tincture 60 56
nitroprusside sodium for injection 59 65
vasopressin, IV and intraosseous 57 63
promethazine, IV 56 59
EPINEPHrine, subcutaneous 51 66*

*2014 survey included subcutaneous and IV EPINEPHrine together

More than 80% of respondents thought these medication classes or specific medications were high-alert:

  • chemotherapeutic agents, parenteral and oral (99%)
  • insulin, subcutaneous and IV (98%)
  • neuromuscular blocking agents (97%)
  • antithrombotic agents (96%)
  • U-500 insulin (96%)
  • potassium chloride for injection concentrate (95%)
  • epidural and intrathecal medications (93%)
  • sodium chloride for injection, greater than 0.9% (88%)
  • opioids, IV, oral, transdermal (83%)

Possible additions and changes. In the survey, ISMP asked respondents about one possible addition to the ISMP list, along with two possible changes to the list (Table 2). Almost three quarters (74%) of respondents agreed that oral solutions of concentrated sodium chloride should be added to the list, and more than half (54%) of respondents thought that IV promethazine should be changed to promethazine injection.  Less than half of respondents thought that ISMP should expand the oral hypoglycemics category to include the newer antidiabetic injectable agents.    

Table 2. Respondents' views about potential additions or changes in 2018 to the ISMP List of High-Alert Medications in Acute Care Settings
Potential Additions or Changes Add or Change?
Yes (%)
concentrate sodium chloride oral solutions 74
promethazine injection 54
antidiabetic agents, oral and injectable 45

Comparison of 2018 and 2014 Survey Results

Differences between 2018 and 2014 surveys. Prior to 2018, ISMP last conducted a survey on high-alert medications in 2014 (Table 1), after which we updated our list based in part on the survey results. When comparing the results of the two surveys, we found some differences in whether practitioners viewed certain medications as high-alert. These differences were greatest for:

  • sterile water for injection (inhalation/irrigation) in containers (excluding pour bottles) of 100 mL or more (35% thought this was a high-alert medication in 2014, 52% in 2018)
  • dialysis solutions, peritoneal and hemodialysis (39% in 2014, 50% in 2018)
  • IV inotropic medications (53% in 2014, 65% in 2018)
  • IV adrenergic antagonists (75% in 2014, 57% in 2018)
  • subcutaneous EPINEPHrine (66% in 2014, 51% in 2018, although the 2014 survey queried about both intramuscular [IM] and subcutaneous EPINEPHrine)
  • inhaled and IV general anesthetic agents (85% in 2014, 71% in 2018)

Roughly, the same percent of respondents reported that there were special precautions in place for the high-alert medications on their organizations’ lists (85% in 2018, 87% in 2014); however, fewer respondents in 2018 felt these precautions were very or mostly effective (75% vs. 89%, respectively).

2018 Changes to the ISMP List

Based on the survey results, review of the literature and error reports, and input from our advisory board, ISMP has made the following changes to its current ISMP List of High-Alert Medications in Acute Care Settings:

  • Examples of antithrombotic agents were expanded to include direct oral anticoagulants currently on the market.
  • LORazepam was added as an example of an IV moderate sedation agent.
  • The category of oral moderate sedation agents for children was revised to include minimal sedation agents, and additional examples were provided, including midazolam and ketamine (using the parenteral form). This also matches the high-alert medication category as stated in our recent ISMP Medication Safety Self Assessment® for High-Alert Medications.
  • The category of oral hypoglycemics was changed to oral sulfonylurea hypoglycemics, and examples were provided, including chlorproPAMIDE, glimepiride, glyBURIDE, glipiZIDE, and TOLBUTamide. This narrows the category to agents that may result in significant hypoglycemia and patient harm if administered in error, as reported to the ISMP MERP. Numerous comments suggesting this change were also submitted through the 2018 survey.
  • IV radiocontrast media was removed from the list given low support for its continued inclusion and a lack of reported adverse events in our database associated with errors (as opposed to adverse reactions due to allergies or renal impairment).
  • IV promethazine was changed to promethazine injection to expand the high-alert medication status of this drug to administration by any parenteral route, including intramuscular (IM). Although Best Practice #13 in the ISMP Targeted Medication Safety Best Practices calls for the elimination of injectable promethazine in hospitals, evidence suggests that the drug is still available in some hospitals. Thus, for now, we are keeping promethazine injection on our high-alert medication list.  

ISMP decided not to add oral solutions of concentrated sodium chloride (e.g., 23.4%) to our list, despite substantial support for its addition in the 2018 survey. We could not find any error reports or literature regarding errors with this formulation of the medication. More to the point, numerous survey comments suggest that practitioners who supported its inclusion on our list confused this oral formulation with parenteral 23.4% sodium chloride for injection, which is already on our list. However, if you are aware of potentially harmful errors with the oral product, or if you use the product orally and have concerns about harmful errors, please let us know and we will reconsider.

We also received suggestions to consider adding about a dozen medications to our list, such as monoclonal antibodies, tranexamic acid, antiseizure medications, antiretrovirals, glacial acetic acid, and dofetilide. We appreciate all the thought that went into making these suggestions. We have carefully evaluated the suggested additions but will not be adding any of them to our list at this time. We understand the importance of keeping the list manageable. However, we will continue to monitor these medications and include them in our next survey if we believe they may need to be added to our list later. 


Again, ISMP thanks all who took the time to complete our survey on high-alert medications. Our updated list can be found on page 5, of the PDF version, and on our website. We hope you will use this list to determine which medications require special safeguards to reduce the risk of errors in your organization. This may include strategies such as standardizing the ordering, storage, preparation, and administration of these products; improving access to information about these drugs; limiting access to high-alert medications; using auxiliary labels; employing clinical decision support and automated alerts; and using redundancies such as automated or independent double checks when necessary.


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