Prostacyclin administration errors in pulmonary arterial hypertension patients admitted to hospitals in the United States: a national survey

Statistical analysis 

The interview results for the 18 PH nurses are presented as descriptive, qualitative data. Frequency distributions for the responses to the nine electronic survey questions are reported. Chi-square or Fisher's exact tests (when expected cell values were <5) were performed to compare error rates and specific error types among centers with a policy of home infusion pump use as compared with hospital pump use. McNemar's test was performed to evaluate the storage of epoprostenol and treprostinil on nursing units. NCSS 2004 was used for the analysis. Where descriptive or qualitative information is presented, errors are not reported around each proportion. The maximum margin of error for the survey is 11%, based on between 87 and 97 responses to each individual question.

Introduction and respondent characteristics 

One nurse or nurse-practitioner from each of 18 pulmonary hypertension centers was approached by telephone, and all 18 agreed to be interviewed. Each of the centers included routinely utilized intravenous prostacyclins, and the nurses who were interviewed were directly involved in patient care; responses are detailed in what follows. Separately, a survey evaluating prostacyclin policies and errors across a larger and more diverse group of respondents was conducted. This survey was completed by 97 respondents from a recipient pool of up to 1,200 individuals (∼8% response rate), and the respondents included 30 physicians, 18 nurse practitioners, 29 nurses, 19 pharmacists and 1 respiratory therapist.

Nursing telephone interviews 

Electronic survey 

Policies 

Ninety-seven respondents completed the electronic survey on prostacyclin administration policies and errors. The prostacyclin experience of their centers varied, but most centers (72%) cared for 10 or more prostacyclin patients (Figure 1). Institution name was provided by 52 respondents, including one duplicate center. Similar to the nursing interviews, policies on pump use and prostacyclin storage varied. More than half (59%) of the respondents kept patients on their own ambulatory infusion pumps, 12% transitioned patients to hospital CADD pumps, and the remaining 28% transitioned patients to regular hospital infusion pumps. Back-up epoprostenol cassettes were stored on nursing units at 65% of the respondent's hospitals, whereas only 28% kept back-up treprostinil on the unit (p < 0.05).

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Figure 1. Number of prostacyclin patients being treated at electronic survey respondent's center.

Errors 

Serious or potentially serious errors were reported by 65 (68%) of the 95 respondents who completed the survey section on errors. Some of the errors resulted in minimal or no symptoms, but 28 (29%) reported errors that led to a serious adverse event, including 9 deaths (Figure 2). The most commonly reported error, described by 31 respondents, involved flushing the dedicated prostacyclin line. Other errors reported by multiple respondents included use of the wrong medication dose due to calculation or concentration error (N = 29), use of a prostacyclin cassette or bag that was intended for a different patient (N = 25), incorrect rate programmed into the infusion pump (N = 24), and pump inadvertently stopped for a period of time (N = 24). There were also 15 miscellaneous errors written in by respondents (Table 1). Three of the 15 written-in errors involved an inappropriate change in patient weight. Prostacyclin infusions are dosed in nanograms per kilogram per minute, but rarely, if ever, should the dosing weight be changed when a patient is admitted to the hospital. Overall error rates were similar regardless of whether home infusion pumps or hospital pumps were used for prostacyclin administration (p > 0.05).

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Figure 2. Error severity, as reported in the electronic survey.

Table 1. Miscellaneous Write-In Errors

	Pump malfunction–medication ran out.
	Two instances of where patients received approximately 0.5 ml “extra” of epoprostenol during a line change, causing flushing, hypotension and headache for about 30 minutes.
	Patient off epoprostenol because of failure to consider line dead space when changing central line.
	Dose infusing is correct but label on syringe was wrong.
	Errors occurred during switch from home to hospital infusion pump, and another error in calculation led to a significantly increased dose.
	Accidental disconnect once.
	Error due to computer defaulting to admission weight vs dosing weight.
	Wrong dose due to using admission weight vs drug initiation weight.
	Patient was given expired cassette.
	Purge syringe (to prime Hickman) was not pulled from mix. Solution was full strength.
	Nurse changed line over and left room, connection not tight and blood on floor.
	Wrong dose due to patient's dose weight changed in calculation resulting in too much or too little prostacyclin.
	Failed IV access for a patient on epoprostenol with a 12-hour “line holiday” during treatment for sepsis.
	Flushing episode occurred due to involvement of a non-PGI2-specific certified nurse.
	Infusing drugs in the dedicated prostacyclin line occurred in the OR by anesthesia.

Potential hospital policy changes 

Although many of the errors relate to a mistake on the part of a nurse or pharmacist, addressing human error alone is unlikely to result in lasting improvements. Instead, best practices should be identified and implemented across centers treating PAH patients. Many centers reported making changes in their prostacyclin administration policies, often after errors, and a summary of these policies is presented in Table 2. The similarities in certain policy improvements across multiple experienced centers adds strength to these recommendations, but evidence-based support is lacking. It is the belief of the present investigators that the most important policies involve limiting the number of epoprostenol and treprostinil back-up cassettes stored on the nursing units at any given time in order to limit the opportunity for a mix-up. Also, requiring a second RN signature, as is commonly done with blood products, seems to be a prudent and important safety measure. These recommendations are intended only to represent a potential starting point for conversations on prostacyclin safety. Further study will be needed to better define best practice guidelines.

Table 2. Potential Hospital Prostacyclin Infusion Policies

	Potential pharmacy policies:
	• Double check all calculations for concentration and infusion rate.
	• Contact the pulmonary hypertension clinic or the patient's specialty pharmacy upon admission to obtain the patient's dose, dosing weight, concentration and pump rate. Confirm with the patient that this is correct, and that the pump is actually going at this rate. If a titration schedule exists, obtain a copy and send it with the patient to the floor; post it in the room next to the patient's bed as well as in the medication record.
	• Ensure pharmacy labels are easy to read including name, date, concentration and pump rate.
	• Ensure that all information is clearly stated in the medication administration record, including the time for next cassette change and whether ice packs are required.
	• If using cassettes, consider using a different color cassette, or a different color or type of label, for treprostinil vs epoprostenol.
	Potential nursing policies:
	• Place markers on the epoprostenol/treprostinil line near connection sites stating “do not flush” and “dedicated epoprostenol/treprostinil line.”
	• Institute a policy where two nurses sign off on the cassette or bag change, as well as any change in infusion rate.
	• Do not keep back-up treprostinil cassettes or bags on the nursing unit unless they can be kept in a secure location, unique to the patient, such as a medication dispensing system. If treprostinil must be kept on the nursing unit and it does not fit in the medication dispensing system, do not store it in the refrigerator with epoprostenol as it does not require refrigeration and increases the opportunity for a mix-up.
	• Decide whether back-up epoprostenol bags or cassettes will be kept on the nursing unit.
	• If a refrigerated medication dispensing system is available, then storage of epoprostenol on the unit is generally desirable so as to be available in an emergency.
	• If only a common medication refrigerator is used, consider whether the risks of mix-up between patients outweigh the benefits.
	• Ask the patient or caregiver to be involved in their care, and confirm name, concentration, dose and pump rate at each cassette or bag change or whenever a rate change is made.
	• Each shift, document that pump is running correctly and at a rate that matches the order on the medication administration record, regardless of whether a new cassette or bag change is due.
	Miscellaneous:
	• Conduct regular, at least annual, pump training for all nurses in intensive-care and telemetry units and any other floors where pulmonary hypertension patients are likely to be admitted. This training may be provided in conjunction with specialty pharmacies, particularly when home infusion pumps are used in the hospital setting.
	• If the hospital has a rapid response team, they should also be trained as experts in the use of the home infusion pumps.
	Policy decisions where risk and benefit are less certain:
	• Decide whether to keep patients on their home infusion pumps.
	• Decide whether to standardize the prostacyclin concentration(s) or match the concentration used by the patient

Limitations 

In the larger electronic survey, approximately 50% of the respondents completed the survey anonymously, making duplicate entries from each center a possibility. However, of the 52 respondents who did leave their center name, only one center was represented twice, suggesting that this was not common. Because each individual may have cared for different patients, we did not remove this known duplicate. We are also unable to report true error rates, as the number of in-patient prostacyclin exposure days for each respondent's center is unknown. Additional study to more quantitatively assess errors and to evaluate additional hospital or ICU days incurred as a result of errors should be considered.

Conclusion 

Similar to our findings, other studies have found that the most common type of medical error is incorrect quantity of drug.4 In this survey we found that serious and even fatal errors with intravenous prostacyclins are not uncommon. We are particularly concerned about the serious adverse events involving mix-up of one patient's medication with another, which was responsible for 1 of the 9 deaths reported and 29 of the serious events reported. Recommendation 7.3 of the Institute of Medicine's (IOM) Executive Summary of To Err is Human (2000) advises the Food and Drug Administration to improve drug safety, both in the pre- and post-marketing arenas.5, 6 These concerns along with the findings in this survey suggest that hospitals should consider standardized prostacyclin administration policies, including ongoing training of staff to decrease the likelihood of a serious event or death. Special consideration will be required for home miniaturized pumps. Because most centers will also have patients on subcutaneous treprostinil infusions, policies should be in place for these infusions as well, as was suggested by Roncesvalles et al.7 The use of prostacyclins for symptomatic PH has resulted in an improvement in quality of life. It appears that achieving safer administration of these compounds is now warranted.