Fortuitous intrathecal injection of tranexamic acid

Sir,

In India, 5.2 million medical errors are happening annually. Medication errors in operation room (OR) include wrong labels, like appearance and location of ampoules, syringes, poor communication, and carelessness.[1,2]

We are reporting two mishaps due to accidental intrathecal injection of tranexamic acid. The first case was a 21-year-old male, American Society of Anesthesiologists (ASA) grade I physical status, who was scheduled for arthroscopic reconstruction of right anterior cruciate ligament tear (case 1). The second case was a 23-year-old primigravida with preeclampsia at 37 weeks of pregnancy who was admitted for emergency caesarean section (case 2). Post spinal sequelae in both cases were noted [Figure 1]. In case 1, the patient recovered without any neurological deficits and in case 2, mother and baby could not be saved.

Figure 1.

Post spinal sequelae

In both the cases, a retrospective analysis of events led to the diagnosis of accidental intrathecal injection of tranexamic acid [2.5ml (250mg) in the first case and 2ml (200mg) in the second case].

In the operation room, most of the medication errors are action-based execution errors that include communication barrier during verbal transmission of orders, orders written in illegible handwriting, look-alike sound-alike (LASA) drugs, wrongly labelled syringe, and carelessness in confirming drug. LASA medications involve medications that are visually similar in physical appearance or packaging and names of medications that have spelling similarities and/or similar phonetics.[3] In our cases, medication error was an action-based execution error due to LASA medications. The ampoules of tranexamic acid and 0.5% heavy bupivacaine were look-alike [Figure 2].

Figure 2.

Ampoules of 0.5% (heavy) bupivacaine and tranexamic acid are shown side by side

Features of intrathecal tranexamic acid as we have observed in our cases are severe pain in the back, buttocks and legs, myoclonus starting in the legs, generalised convulsions, severe tachycardia, hypertension, and ventricular arrhythmias without any sensory or motor block as we expect on intrathecal bupivacaine administration. Severe gluteal and leg pain and myoclonus may be due to increase excitability secondary to inhibition of Gamma-Amino Butyric Acid (GABA) type A and glycine receptor at post synaptic site of spinal dorsal horn neurons. Subsequently, inhibition of these receptors in the brain will cause cerebral vasoconstriction, ischemia, raised intracranial pressure (ICP) and generalised tonic-clonic convulsions.[4] Cardiovascular changes following intrathecal tranexamic acid could be due to centrally mediated massive sympathetic stimulation.[5] Intrathecal administration of 1 g of tranexamic acid evenly distributed throughout the normal 150 ml of cerebrospinal fluid (CSF) and expected to produce a CSF concentration of approximately 6600 μg/ml which is approximately 7000 times higher than after intravenous injection.[6]

Once intrathecal injection of tranexamic acid is identified, subsequent management should be aggressive and must include anticonvulsants, intensive haemodynamic monitoring, repeated arterial blood gas (ABG) analysis and, possibly, CSF lavage.[6]

Patel et al. reviewed 21 cases of accidental spinal administration of tranexamic acid and observed this in seven elective lower segment caesarean section (LSCS), six orthopaedic, and eight general surgery cases. Of them, 10 patients died and remaining 10 required intensive care admission for management of refractory convulsions and/or tachyarrhythmias. In almost all the cases, errors were related to the similar size and appearance of the ampoules of tranexamic acid and bupivacaine. Only in one case, confusion between the IV line and a spinal catheter led to the error.[6]

As noted in the global data, we had a similar experience, that the orthopaedic patient recovered without any neurological deficit, but the obstetric patient could not, as peripartum physiology is different and complex from a normal healthy individual. Pregnancy reduces CSF volume as well as the dural sac surface area, facilitating the spread of local anaesthetic and may result in higher concentrations of tranexamic acid in CSF. Most maternal deaths occurred within hours of receiving spinal tranexamic acid due to more profound and early cerebral effects.

After these incidents, we wrote to the manufacturer and government to consider a change in ampoule look and to implement colour coding. Double checking, loading full drug from ampoules (since tranexamic acid is 5-ml ampoule and bupivacaine is 4-ml ampoule, so a left-over drug after loading 4ml should arouse suspicion before injecting), call out of each drug before delivery, and maintaining closed-loop communication were made mandatory. The awareness programs were organised regularly regarding drug errors and their prevention.

We conclude that whenever severe back and gluteal pain, myoclonus, generalised convulsions, severe tachycardia, hypertension, and ventricular arrhythmia are observed without any sensory or motor block after spinal anaesthesia, one should have a suspicion of wrong drug administration and manage aggressively.

Declaration of patient/guardian consent

The authors certify that they have obtained all appropriate patient/parent consent forms. In the form, the patient/guardian has/have given his/her/their consent for images and other clinical information to be reported in the journal. The patient/parents understand that the names and initial will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.