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We’ve done columns on the devastating consequences of inadvertent spinal injection of tranexamic acid (see our Patient Safety Tips of the Week for June 4, 2019 “Medication Errors in the OR – Part 3” and July 9, 2019 “Spinal Injection of Tranexamic Acid”).
ISMP Canada just issued a safety alert about another such incident (ISMP Canada 2022). (Actually, the error in this incident was identified only when the same error occurred during a subsequent procedure later in the day.) The patient was scheduled for an orthopedic surgical procedure. In the operating room, tranexamic acid was inadvertently injected into the cerebrospinal fluid, instead of the intended local anesthetic bupivacaine. The patient reported extreme pain and demonstrated unusual movements during the procedure, and experienced seizures while in the recovery room. The patient remains bed-bound and is living with extreme chronic pain.
At the time of the incident, both tranexamic acid and bupivacaine were stored in the same drawer of the drug cart. The hospital’s investigation found that a form of confirmation bias (“seeing what you expect to see”) likely contributed even though a double check had been performed. And it was investigation of an open bin of discarded vials (after the second patient was affected) that confirmed that tranexamic acid had been mistakenly administered to the first patient. The ISMP Canada alert does not mention whether barcoding was available in that OR there or not.
In our June 4, 2019 Patient Safety Tip of the Week “Medication Errors in the OR – Part 3” we happened to mention the inadvertent spinal administration of tranexamic acid as one of the medication errors occurring in the OR setting. Tranexamic acid is an antifibrinolytic agent used in the control of traumatic, surgical, and obstetric hemorrhage. In 2015, Patel and Loveridge (Patel 2015) did a review of obstetric neuraxial drug administration errors. That review included four deaths from spinal tranexamic acid administered at caesarean section. At that time, they had four key recommendations to avoid such errors:
1. careful reading of the label on any drug ampule or syringe before the drug is drawn up or injected
2. labeling all syringes
3. checking labels with a second person or a device (such as a barcode reader linked to a computer) before the drug is drawn up or administered
4. use of non-Luer lock connectors on all epidural/spinal/combined spinal-epidural devices.
Then, in our July 9, 2019 “Spinal Injection of Tranexamic Acid”, we discussed a more recent review by Patel et al. (Patel 2019). They identified 21 reports in the literature of accidental spinal administration of tranexamic acid injected during spinal anesthesia or analgesia. These included seven elective caesarean sections and six patients having orthopedic surgery. Death was reported in 10 patients, and 10 of the remaining 11 patients required intensive care admission for management of refractory convulsions and/or tachyarrhythmias.
Typical symptoms and signs include severe pain in the back, buttocks and legs, myoclonus starting in the legs, generalized convulsions, severe tachycardia and hypertension, and ventricular arrhythmia. In addition, there was usually no sensory or motor block as you’d expect if the intended bupivacaine had been administered.
In almost all cases there was an error related to the ampule containing the tranexamic acid. There was similar size and appearance to the ampules of the intended medication (usually bupivacaine or similar agent). Failure to check the label contributed in many cases. One case involved confusion between the IV line and a spinal catheter that had been inserted for chronic pain management.
Some organizational factors that were reported included a lack of formal drug handling or storage policy, and lack of resources. In three cases, syringes or vials containing tranexamic acid were prepared by personnel other than the practitioner administering spinal anesthesia. On one occasion, the tranexamic acid ampule was stored in the same location as local anesthetics. The ampule was passed unchecked from the assistant to the anesthetist, who also failed to check the ampule.
Patel et al. note that all errors could have been prevented if the recommendations in their 2015 paper had been followed. They also suggest that manufacturers of tranexamic acid should be encouraged to design ampules with recognizable size, shape, fonts and color or, alternatively, tranexamic acid might be manufactured in a vial. The also advise that tranexamic acid, and other non‐anesthetic drugs, should be stored in a separate location in or outside the operating room, to limit the possibility of picking up the wrong drug.
Our previous columns on medication errors in the OR have noted one critical factor contributing to many incidents is that one person (the anesthetist) often orders the medication, prepares it, and administers it. That bypasses the usual chain in the medication administration system in which you have several sets of eyes (physician, pharmacist, and one or more nurses) checking the medication. Double checks would be an obvious potential solution, but a double check failed in the current Canadian case. We don’t see many OR’s in which such double checking actually occurs. Also, barcoding could go a long way to avoid such misadministration. But many OR’s have yet to implement barcoding (see our June 2022 What's New in the Patient Safety World column “Where Are You Barcoding?”).
In an editorial accompanying the 2019 Patel study, Palanisamy and Kinsella (Palanisamy 2019) focus on two important points: (1) reducing the similarity of the ampules and (2) segregating the storage of the drugs. They noted that tranexamic acid and bupivacaine are both patent‐expired drugs that are supplied by a surprising number of generic manufacturers. They stress that ampules of similar size increase the likelihood of mistakes and suggest manufacturers could make ampules distinctive with different colored neck and head rings in addition to the labelling issues. They also stress that facilities should physically segregate tranexamic acid from commonly administered spinal medications. Because tranexamic acid is not frequently administered, it can be housed in a location that is distinct from anesthetic drugs. Note that we (in our June 4, 2019 Patient Safety Tip of the Week “Medication Errors in the OR – Part 3”) and Patel et al. in the above paper have suggested tranexamic acid might be stored outside the OR. But Palanisamy and Kinsella make a plea not to banish tranexamic acid from the labor and delivery ward and operating room. They note tranexamic acid is a safe, inexpensive and modestly effective treatment and that the number needed to treat for IV tranexamic acid to prevent one maternal death from hemorrhage is 267, whereas the number needed to harm for inadvertent administration of tranexamic acid would be much higher.
A NAN (National Alert Network) Alert in 2020 described 3 additional cases of accidental spinal injection of tranexamic acid instead of a local anesthetic intended for regional (spinal) anesthesia (NAN 2020). Container mix-ups were involved in each case. In each case, seizures occurred shortly after the inadvertent spinal injections.
In that NAN alert, ISMP notes that it had previously described 3 such cases (ISMP 2019) and pointed out that the similarity of vials of tranexamic acid to those of the local anesthetics was a key contributing factor. Moreover, these cases are often being performed in areas where barcoding has not been implemented (see our June 2022 What's New in the Patient Safety World column “Where Are You Barcoding?”). And, in some cases, syringe labeling issues may be contributory factors.
Even the orientation at which you store the vials may be important. The NAN alert notes “While label colors and vial sizes are different, the caps on ropivacaine, bupivacaine, and tranexamic acid vials may have the same blue color and could lead staff to select a vial based on cap color, without reading the label, especially if the vials are stored upright with only the caps showing.”
The NAN alert recommended the following prevention measures:
The hospital in the recent Canadian case immediately issued a safety alert, both hospital-wide and province-wide. They suggested the following strategies:
Note that the hospital also began providing tranexamic acid for injection in glass ampules to differentiate it from medications in vials, but acknowledged that there have been case reports of mix-ups between ampules of tranexamic acid and local anesthetics.
ISMP Canada had these further recommendations:
The ISMP Canada alert also has an important point we made in our columns on response to serious incidents – seizing and sequestering any evidence when an adverse incident occurs (see our Patient Safety Tips of the Week for July 24, 2007 “Serious Incident Response Checklist” and May 31, 2022 “NHS Serious Incident Response Framework”). The involved hospital only identified the nature of the error when they found discarded vials of tranexamic acid from the second case. The alert recommends each facility develop a method of disposal in the operating room that enables the review of discarded vials following a critical incident, while ensuring adherence to medical waste disposal policies.
Our June 2022 What's New in the Patient Safety World column “Where Are You Barcoding?”) was basically a plea for all hospitals to extend their barcoding capabilities to areas such as the OR and radiology suites. It is unfathomable that our most powerful medication safety tool is not being used where medications are frequently administered.
And, while we still recommend use of double checks when administering anything spinally, the current Canadian case illustrates that double checks often fail.
A key point we always make is “Don’t store dangerous medications in a location where someone might inadvertently pick it up, prepare it, and administer it”. We learned that lesson many years ago when concentrated potassium chloride was sometimes inadvertently given IV to patients, resulting in fatalities. We also stressed it in our columns (listed below) on the mistaken administration of methylene blue instead of the intended trypan blue in ophthalmology cases. But tranexamic acid is being used more frequently in a variety of procedures, so it may not be practical to eliminate it from most OR or labor and delivery settings. That editorial by Palanisamy and Kinsella (Palanisamy 2019) provides a strong argument against banishing tranexamic acid from the OR or labor and delivery suite. However, hospitals could still do an inventory of use of tranexamic acid in each of their OR’s and selectively remove tranexamic acid from those that almost never use it. For example, an OR that is dedicated to ophthalmology cases might never use it. You could still store tranexamic acid in your labor and delivery rooms and those other OR’s where it is frequently used, while still making sure it is not stored in proximity to your anesthetic drugs.
If your facility uses tranexamic acid, it would be wise to perform a FMEA (failure mode and effects analysis) to identify and mitigate any current vulnerabilities you find.
Some of our prior columns on inadvertent spinal administration of tranexamic acid:
June 4, 2019 “Medication Errors in the OR – Part 3”
July 9, 2019 “Spinal Injection of Tranexamic Acid”
Some of our prior columns on medication errors in the OR:
March 24, 2009 “Medication Errors in the OR”
May 20, 2014 “Ophthalmology: Blue Dye Mixup”
September 2014 “Another Blue Dye Eye Mixup”
November 3, 2015 “Medication Errors in the OR - Part 2”
June 4, 2019 “Medication Errors in the OR – Part 3”
ISMP Canada. ALERT: Substitution Error with Tranexamic Acid during Spinal Anesthesia. ISMP Canada Safety Bulletins 2022; 22(6):
Patel, S, Loveridge, R. Obstetric neuraxial drug administration errors: a quantitative and qualitative analytical review. Anesthesia and Analgesia 2015; 12: 1570-1577
Patel S, Robertson B, McConachie I. Catastrophic drug errors involving tranexamic acid administered during spinal anaesthesia. Anesthesia 2019; 74(7): 904-914 First Published: April 15, 2019
Palanisamy A, Kinsella SM. Spinal tranexamic acid - a new killer in town. Anaesthesia 2019;74(7): 831-833 Epub April 15, 2019.
NAN (National Alert Network) Alerts. Dangerous Wrong-Route Errors with Tranexamic Acid. ISMP 2020; September 9, 2020
ISMP (Institute for Safe Medication Practices). Dangerous Wrong-Route Errors with Tranexamic Acid—A Major Cause for Concern. ISMP Medication Safety Alert! Acute Care Edition 2019; 24(10): May 23, 2019
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