Article Notes
- 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.
- 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.
- 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...
- Block failure.
- Severe back and buttock pain (universal).
- Seizures.
- HT, tachycardia, arrhythmias, CVS collapse.
- 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
- 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.
What is the Quadratus Lumborum Block (QLB)?
The quadratus lumborum muscle is the deepest abdominal wall muscle, running posteriorly, dorsolateral to psoas major. Three different types of QLB have been described
What's the deal with QLB for Cesarean section?
QLB is interesting because it may offer analgesia for visceral pain after caesarean section, in addition to somatic pain. Visceral pain may be a significant contributor to post-CS pain experience, and is not blocked by existing adjuvant techniques such as the transversus abdominal plane (TAP) block.
The proposed effect of QLB on visceral pain may be due to local anaesthetic spread to the paravertebral space, although evidence confirming this is scant and suggests it occurs only in small volumes and inconsistently at best.
Additionally, as with the demonstrated inadequacy of objective sensory block from a TAP block, studies of the sensory level effects of QLB also show limited actual sensory block – even if the QLB has shown some analgesic benefit in some studies.
Some QLB studies have shown analgesic benefit for post-CS patients, although most are small studies. At this stage it appears unlikely that QLB provides routine analgesic benefit for patents already receiving standard-of-care multimodal analgesia in combination with a neuraxial anaesthetic for caesarean ection.
Daniel Jolley
Why is this important?
This is the first systematic review of RCTs assessing different techniques for conducting awake fibreoptic intubation (AFOI), although the quality of evidence continues to be moderate-low.
Cabrini et al. reviewed 37 RCTs capturing 2,045 AFOI events.
What did they find?
There was no significant success difference among techniques for either local anaesthesia application or procedural sedation, including infusions or boluses of dexmedetomidine, propofol, opioids (fentanyl, sufentanil, remifentanil), ±midazolam, or sevoflurane.
Dexmedetomidine sedation resulted in the fewest desaturation events, and sevoflurane the fewest apnoea events.
Opioids used on their own (ie. without benzodiazepines) resulted in the highest patient recall, particularly remifentanil.
Also of interest...
When conducted by trained experts, AFOI is safe and effective regardless of technique and only very uncommonly results in intubation failure (0.59%) or severe adverse events (0.34%). No permanent morbidity or death was identified.
The take-home message:
When choosing a technique for awake fibre optic intubation, do what you do best – generally this will be what you and your institution are most experienced with.
Daniel Jolley
Why is this a landmark trial?
Three reasons:
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.
Daniel Jolley
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?
Daniel Jolley
A sobering editorial...
Daniel Jolley
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?
How should it be managed?
There are three components to managing intrathecal TXA:
How does this happen?
In almost all cases ampoule identification error was the primary cause.
Human factor contributions identified were:
"All errors could have been prevented..."
Daniel Jolley