A Case Report From the Anesthesia Incident Reporting System

“If you put the federal government in charge of the Sahara Desert, in five years there’d be a shortage of sand.” – Milton Friedman

Outsourced (Pharmedium) hydromorphone syringes were unavailable due to a drug shortage. Pharmacy-prepared hydro-morphone syringes were substituted, but lacked the blue (opioid) color coding on the label. In addition, pharmacy-prepared hydromorphone syringes were the same size syringe (5 ml in a 6 ml syringe) with a similar pharmacy label as dexmedetomidine syringes. Pharmacy did not vet this change with anesthesia providers before implementation to determine if the change was safe. On at least three occasions, hydromorphone was inadvertently administered instead of dexmedetomidine (prepared in the same size syringe with similar pharmacy labeling). On one occasion, a partially used hydromorphone syringe was thought to be dexmedetomidine and discarded instead of returned to pharmacy for controlled substance accountability. There were several near-misses.

This case illustrates at least three significant patient safety issues: the first is the seemingly ubiquitous and eternal drug shortages; the second is the variable application of color-coded syringe labels for anesthesia drugs; the third centers on communication failures, in this case between pharmacy and anesthesia providers.

Drug shortages began to appear with some regularity in the early 2000s and seemed to peak in 2011 at 267 reported for the year (Figure 1). The FDA defines drug shortages somewhat differently than the American Society of Health-System Pharmacists (ASHP), so the ASHP numbers are always greater than the FDA numbers. Hydromorphone would not have been counted as a drug shortage by the FDA, as there are alternatives (morphine, methadone, fentanyl); but as shown above, even an available alternative raises significant risks, as the alternative will have a different potency, may be less effective and have a different side-effect profile. Substitutions by the pharmacy, if not clearly and effectively communicated, can lead to significant confusion if pharmacists are unable to avoid look-alike vials or ampoules.

Substitutions may increase mortality. Among 27,835 patients with septic shock in 26 hospitals, patients admitted during times of norepinephrine shortage had an increased rate of in-hospital mortality compared to patients admitted during periods of normal supply (39.6 percent versus 36.9 percent), an absolute risk increase of 3.7 percent (P = .03).¹  Chemotherapy drugs carry perhaps the greatest risk, with some studies indicating worse outcomes with alternative drugs,²  and others showing no apparent affect.³  Whether drug shortages actually imperil health is not clearly known, but all agree that drug shortages are extremely costly, due to both more expensive drugs required as substitutes and the significant impact on pharmacist time to continually track shortages, search out alternatives and educate staff members in potential shortages. The National Health Service (U.K.) estimates that drug shortages cost the system £38 million in a single month.⁴  Anesthesiologists certainly have felt the impact of shortages, particularly now, with local anesthetics (bupivacaine and ropivicaine) in current short supply. Many institutions are altering which regional analgesic techniques will be favored or substituted (e.g., Exparel^TM quadratus lumborum blocks in lieu of epidural or paravertebral blocks) in order to reserve bupivacaine or ropivicaine for obstetrical epidurals.

The second serious patient risk illustrated by this example is that of syringe labeling and the presence or absence of colored labels. The use of various colored syringe labels to provide a visual cue to the class of drug in the syringe has been around for at least 25 years. U.S., Canadian and Australian groups adopted the standardized color code system (Figure 2, page 44) promoted by the American Society for Testing and Materials (ASTM) prior to 2000; unfortunately, Great Britain and Ireland had, in 2002, a plethora of different local systems for color-coding anesthesia syringes.⁵  Trying to adopt to a single, uniform color code system actually increased the rate of drug errors for a time, until all anesthetists became familiar with the new system.⁶  The errors in this incident report were due, in part, to the absence of the expected blue opioid class label on pharmacy-prepared syringes of hydromorphone, and confusion with a plain white label that was very similar to that on pharmacy-prepared dexmetatomedine.

Colored labels are, at this time, ubiquitous in American anesthesia practices, whether on prefilled syringes from an outside provider such as Pharmedium, CAS or by a local provider who draws up their own medications. Virtually all of us adhere to the ASTM standards, which have now become an international standard as well (see text box). Unfortunately, not all agree that color coding labels is appropriate, and so many pharmacists do not color code prefilled syringes for anesthesia use – but, as in this case, simply use a plain white label. The Institute for Safe Medication Practices (ISMP) does promote the use of colored labels by anesthesiologists in the O.R., but they, together with ASHP and the AMA, oppose the use of colored labels for commercially available drugs.⁷  Their contention is that the myriad of different drugs within a single drug class make reliance on the label color a risky business. Anesthesia providers typically only use one or two drugs within a drug class, so mix-ups are less common. Copper is the color for cardiovascular drugs; in the O.R., anesthesia providers typically only use a small subset of what is available, but in the ICU there may be many more drugs of this class used, with increased confusion. The concern that using color-coded labels might promote errors may come from the experience with ophthalmology, who reported a significant number of errors when colored labels were used.⁷  The ISMP and ASHP strongly suggest that anesthesiologists only use the colored labels within the O.R. and use plain white labels on syringes when in the ED or ICU. There is little evidence and few case reports of color-coded labels resulting in errors in these locations, but this caution is the reason the pharmacy-prepared syringes always come with a plain white label. The pharmacy mantra is “Read the label!” Unfortunately, the “plain white labels” typically used by pharmacies 1) contain much information that is not germane to an O.R. setting and 2) the drug name is VERY small – a sure recipe for disaster (or near-disaster, as in this case). Furthermore, most human factors experts would recognize that instructing us to “be more careful” or “pay attention” is a sure recipe for medication errors. While an anesthesiologist might give fentanyl in error when hydro-morphone was intended, the blue color cue would have at least gotten the patient a narcotic and not a neuromuscular blocker. Admonitions from pharmacy and an insistence on providing all prepared syringes with plain white labels may be short-sighted and possibly dangerous. An individual anesthesia provider could, of course, add a colored label, but at the expense of time and potential for confusion at that step.

The final patient safety risk, or system vulnerability, was the lack of communication from the pharmacy about the shortage of prefilled hydromorphone syringes and that the substituted medication would have a simple white label rather than the expected blue label. In at least one hospital system (University of Michigan), a staple of the Thursday M&M is five minutes from the O.R. pharmacist about the latest shortages, and what the new substitutes will be, together with slides showing how the substitute will look. In cases where look-alike vials had to be purchased, this was called out clearly. It has also been suggested that anytime a significant substitution is made for a familiar drug, the substituted vial, ampoule or syringe be in the appropriate location in the drug tray, but be placed in a red bag that identifies it as a substitute, or bears some sort of clear warning that this is not the usual drug. We all do understand the “alert fatigue” that comes with repeated updates, but these must become part and parcel of our lives as long as drug shortages persist. Each anesthesia department should set an ad hoc committee to design a local system of communicating shortages and how the shortage will be addressed (local compounding, breaking multi-use vials into syringes in the pharmacy, substitutions) and substitutions announced.

Ultimately, the use of bar coding will significantly enhance our safety. While humans can misread labels, the computer rarely misreads a bar code. A comprehensive medication safety system that includes bar coding of syringes, together with visual and audio alerts, has been shown in both the real world and in simulation to decrease the number of medication errors.^8,9  When bar coding becomes widespread, anesthesiologists will have at least three different cues to what is within the syringe: a visual display of the drug name, the audible identification of the drug and concentration, and the color-coded label. But, in the end, the final admonition, which is the absolute minimum standard for competence, is that providers take the time to actually read the entire label of every syringe, ampoule or vial and verify that it is the one they intended, prior to administration.