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Created August 7, 2019, last updated almost 2 years ago.
Collection: 108, Score: 1482, Trend score: 0, Read count: 1809, Articles count: 7, Created: 2019-08-07 00:00:08 UTC. Updated: 2022-12-31 15:48:53 UTC.Notes
Why the excitement?
Since the landmark 2017 WOMAN trial (collected below) showed that tranexamic acid (TXA) may reduce mortality in post-partum haemorrhage, TXA has increasingly been found in close proximity to where obstetric spinal anaesthetics are commonly performed.
TXA's operating theatre ubiquity has also been enhanced by it's replacement of aprotonin in cardiac surgery (Myles 2017, Koster 2015), after the former's associated mortality bump, along with the increasingly routine use of TXA in major joint surgery to reduce bleeding and transfusion (Ho 2003, Poeran 2014).
Recent reviews have identified 21 case reports of mistaken intrathecal administration of TXA over 60 years of anaesthetic publications – although it is likely many cases have been unreported.
Seems rare - why should I be concerned?
- Intrathecal TXA has a 50% mortality, and frequently leaves survivors with permanent neurological injury.
- Once recognised, immediate, aggressive management may improve outcome (particularly, CSF lavage).
- Although rarely published, the increased use of intra-operative TXA may bring it into close proximity with common intrathecal drug ampoules, increasing the risk of this devastating error. Case report publication dates support the increasing incidence.
- Knowing the potential for this error is the first step to avoiding it both personally and systemically.
- Almost all cases involve drug swap errors with major human factor contributions.
Daniel Jolley
Another useful review of neuraxial tranexamic acid, although not indexed by pubmed. Full-text below:
Gupta et al., Tranexamic acid: Beware of anaesthetic misadventures, J Obst Anaesth Crit Care 2018.
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Collected Articles
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What did they find?
This review by Patel, Robertson & McConachie identified 21 published cases of inadvertent spinal TXA administration. Notably 10 patients died, and almost all suffered life-threatening side effects.
What are the common signs?
- Block failure.
- Severe back and buttock pain (universal).
- Seizures.
- HT, tachycardia, arrhythmias, CVS collapse.
How should it be managed?
There are three components to managing intrathecal TXA:
- Treating TXA-induced seizures with anticonvulsants: magnesium; benzodiazepines; barbiturates (thiopentone); phenytoin; possibly propofol. Thiopentone infusion was frequently required to terminate seizures.
- Mitigate TXA neurotoxic effects: maintain head-up; CSF lavage to dilute TXA, infusing crystalloid at an interspace higher than an IT needle draining CSF, 10mL for 10mL, repeated up to 4 times.
- Haemodynamic monitoring & support
How does this happen?
In almost all cases ampoule identification error was the primary cause.
Human factor contributions identified were:
- Failure to check ampoule label.
- Similar ampoule appearance.
- Spinal catheter mistaken for IV (1).
- Lack of drug handling and storage policies.
- Storage of tranexamic acid with LA or lack of physical separation.
- Underestimating potential for error.
summary"All errors could have been prevented..."
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A sobering editorial...
- Since 2009 there has been a dramatic increase in reported cases of intrathecal tranexamic acid (TXA), parallel to increasing intraoperative TXA use.
- TXA is powerfully neurotoxic.
- Spinal TXA has a mortality rate > 50%, and high incidence of permanent neurological injury in survivors.
- Almost always results from a drug swap error.
- Because both TXA and bupivacaine are made by many manufacturers, there are many different ampoule designs and drug presentations.
- Risk of harm from TXA error is probably ~ 1 in 10,000 spinals.
- TXA should be physically separated from common spinal drugs and we should consider discarding orphaned ampoules rather than attempting to return to the box.
- Stop and visualise the consequences after your own theoretical spinal drug error: facing the patient, family, colleagues, hospital, regulators...
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Anesthesia and analgesia · Dec 2015
Review Case ReportsObstetric Neuraxial Drug Administration Errors: A Quantitative and Qualitative Analytical Review.
A systematic review of 29 published cases of neuraxial obstetric drug errors, including four maternal deaths related to inadvertent intrathecall tranexamic acid.
What’s the first warning sign of an intrathecal drug error?
Block failure was the most frequent reported complication.
What were the most common human factors causing the errors?
- Similar drug ampoule appearance.
- Drug storage problems.
Any recommendations to reduce the risk of drug errors?
- Carefully read the ampoule before drawing up, and the syringe label before administering.
- Label syringes!
- Check labels with a second person or a device.
- Use non–luer lock connectors on all neuraxial catheters & devices.
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The Department of Health aims to eliminate the use of devices with a Luer connector firstly from 'single shot' neuraxial procedures (April 2012) and subsequently from all neuraxial and regional anaesthesia procedures (April 2013). This initiative is important for all anaesthetists, oncologists, paediatricians and neurologists. Once achieved, non-Luer connectors for neuraxial procedures will create one more barrier to wrong-route errors. ⋯ A structured evaluation of all five current connectors is urgently needed. Non-Luer connectors, however successful, will not create barriers to several type of wrong-route error and solutions to these should also be actively sought. It is clear that the initiative has been more complex than the Health Select Committee, the National Patient Safety Agency and the External Reference Group anticipated, but while there is still much work to be done, we should acknowledge that much progress has been made.
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Randomized Controlled Trial Multicenter Study
Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.
Why is this a landmark trial?
Three reasons:
- Clinical significance of the findings: reducing maternal mortality.
- Relevance to much of world's population, in particular to low resource settings where post-partum haemorrhage (PPH) is disproportionately burdensome.
- Quality – a massive, double-blinded randomised controlled trial.
So, what did they do?
They randomised 20,060 women with PPH to receive either 1g of tranexamic acid (100mg/min slow IV) or placebo, across 21 countries and 193 hospitals. Although only 569 (2.8%) patients were from a high resource country (UK).
What did they find?
Mortality due to haemorrhage was reduced by almost 20% (RR 0.81, NNT 267) after receiving tranexamic acid (TXA), and by 30% (RR 0.69) when given within 3 hours of birth.
Hysterectomies were not reduced by TXA use. There was no increased risk of thromboembolic events.
Be smart
While on the surface this suggests we should move to routine use of TXA in managing all PPH, the risk of PPH-death in most high resource countries is relatively low. 99% of all PPH deaths are in low resource countries.
In the WOMAN trial the risk of death in the placebo group was 1.9%. In contrast the latest maternal mortality data from MBRACE-UK (2014-16) reports 0.78 haemorrhage-deaths per 100,000 maternities, which using a conservative 5% PPH incidence (depending on definition), yields a PPH-mortality risk of 0.016% – 100x less than the study population.
Thus in a high resource setting the TXA NNT to avoiding one maternal death is generously at least 20,000 PPH cases.
In high resource settings, TXA use should be considered second-line therapy in managing severe PPH when other measures are inadequate. In low resource settings where maternal PPH mortality Is high, TXA reduces maternal mortality and should be routinely used.
Context is everything.
summary -
The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. ⋯ How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality.