Hospitals need to look no further than their own organization to clearly see the adverse effects of ongoing nationwide shortages of critical medications that threaten patient safety and health. Plaguing the provision of healthcare for years, costly drug shortages have become increasingly frequent, occur with little or no warning, and often result in ethics-entangled rationing of available supplies, compromised or delayed drug therapy, harmful errors, and other adverse outcomes.
ISMP conducted a survey in November and December 2013 on drug shortages involving essential components needed to prepare parenteral nutrition (PN). We wanted to learn how the shortages of key components of PN have affected healthcare providers and patients, and how the US market has reacted to foreign products imported by the US Food and Drug Administration (FDA) to help ease these shortages. We sincerely thank the 234 practitioners, mostly pharmacists (81%) and other pharmacy staff (8%), who participated in the survey. Here’s what they had to say.
Errors and adverse outcomes
Depending on the PN component in short supply, anywhere from 3% to 28% of survey respondents reported medication errors associated with the inability to obtain these products or when using an alternative product during a shortage (see Table 1 on page 3 in the PDF version of the newsletter). These medication errors were most often linked to shortages of trace elements, sodium phosphate, potassium phosphate, multi-vitamins, calcium gluconate, and IV fat emulsion. Overall, 1 in every 4 to 5 respondents reported preventable adverse outcomes due to these shortages.
Deficiencies in patients’ serum levels associated with electrolytes, minerals, trace elements, vitamins, and amino acids were most often caused by omitted or delayed administration stemming from severe shortages of these products. With rationed PN components, changes from daily to alternating days for needed components sometimes led to omissions caused by the variability of the administration schedules (e.g., Monday, Wednesday, Friday). Some respondents reported that, in the absence of calcium gluconate, they administered calcium chloride peripherally (calcium chloride has an increased risk of precipitating with phosphate if mixed in PN). A few respondents reported extravasation with severe necrosis or accidental continuation of the peripheral infusions after PN discontinuation. A few also reported worsening anemia in patients who did not receive copper chloride, and bone fractures in infants who did not receive adequate phosphorous or other key minerals or vitamins.
Common contributing factors with reported errors included: mix-ups between electrolyte salts, confusion between pediatric and adult alternative products, differences in concentration with alternative products, or forgetting to make changes to protocols, templates, work labels, compounders, or order entry systems reflecting the differences in concentrations or components in an alternative product. Mix-ups when loading products on a compounder and overriding barcode scanning warnings allowed some errors to reach patients. Other examples of errors reported by respondents can be found in Table 1 (on page 3 in the PDF version of the newsletter.
Use of imported PN replacement products
During the past year, 68% of survey respondents reported using at least 1 of 6 products imported into the US after FDA exercised regulatory discretion to ease the shortages of critical PN components. Adult multi-trace elements (ADDAMEL N, 59%), organic phosphate injection (GLYCOPHOS, 49%), and 20% IV fat emulsion (36%) were the most frequently used imported products. Zinc gluconate injection (18%), calcium chloride injection (18%), and pediatric multi-trace elements (PEDITRACE, 28%) were the least frequently used imported products. Overall, half of the survey respondents found FDA importation of critical drug products during the shortage to be helpful (26%) or very helpful (24%) in meeting patient needs.
Those who had used an imported product during the past year were asked to report problems associated with these products. Expense was among the top 3 problems identified for all 6 of the imported drugs noted above. With pediatric and adult multi-trace elements, and phosphate injection, respondents also felt that differences in the products (not an exact equivalent to the US products) were problematic. The most frequently reported problem besides expense for calcium chloride injection, zinc gluconate injection, and IV fat emulsion was that the products required additional steps to prepare and dispense. Respondents also reported problems using the calcium chloride injection with current automation, too much waste with the zinc gluconate, and long delays in receiving the fat emulsion. Respondents reported more problems and errors (13%) with phosphate injection than the other imported products.
The most frequent reasons provided by respondents who did not use at least 1 imported product during the past year included not needing the products and concerns about safe use. Compatibility, stability, and sterility concerns were also cited with imported products, particularly adult multi-trace elements, phosphate injection, and calcium chloride injection.
Numerous safety risks and preventable adverse outcomes have been associated with shortages of critical PN components. Overall, FDA importation of drugs during dire shortages can be very helpful for specific drugs, and we hope recent efforts will be viewed as a much needed back-up plan without which we would not have been able to treat many critically ill patients. However, FDA importation of drugs is not without its challenges. Imported products will continue to present certain risks, including, for example, difficulties associated with checking for drug interactions (imported products may not be listed in drug information systems), and issues with product packaging, labeling, and barcode scanning. To be successful, importation would ideally provide healthcare providers with better access to products that are more similar to the drug in short supply, and in a more timely manner. (The PN component shortage improved before some imported products were available.) Also, waste and stability issues need to be addressed, and the costs associated with imported products cannot be prohibitive.