Tranexamic acid at cesarean delivery: Curbing drug-error deaths

The World Health Organization recommends tranexamic acid (1-g) intravenously over 10 minutes, within 3 hours, for treating postpartum hemorrhage (PPH), unless contraindicated. This recommendation is based on evidence of reduced mortality compared with placebo and has been included in national guidelines such as those in South Africa.

The implementation of this recommendation, intended to improve the care of women with PPH, has exposed an unanticipated but important risk associated with increasing tranexamic acid use within obstetrical care. The increased use of tranexamic acid in the operating room to control bleeding at cesarean delivery seems to be associated with increasing numbers of inadvertent intrathecal administrations. In anticipation of its use at cesarean delivery, tranexamic acid ampoules are now frequently kept in the anesthetic drug trolley in the operating room, creating a risk of tranexamic acid being mistaken for a spinal anesthetic drug and injected intrathecally before cesarean delivery. The risk of this drug error is heightened by the similarity in shape and size of the ampoules containing tranexamic acid and those containing drugs used for spinal anesthesia (eg, bupivacaine).

This potential drug error was highlighted, and recommendations to prevent it outlined in a 2019 publication following the identification of a fatal case through a South African confidential inquiry into maternal deaths. The authors are aware of 3 cases that occurred in South Africa during December 2021 and January 2022, raising concern that the problem may be more widespread than published case reports would suggest. Two were fatal, and one associated with prolonged ventilation and neurologic injury. Colleagues have informed of similar instances in other countries. The true extent of the problem is difficult to measure because clinicians and managers may be reluctant to report errors that lead to major adverse outcomes. Furthermore, in some cases, the drug error may not be recognized because anesthetic practitioners may be unaware of the acute neurotoxic effects of intrathecal tranexamic acid. For example, in 1 of the 3 recent cases, the presentation of convulsions and cardiovascular instability after administration of the spinal anesthetic was ascribed to eclampsia by the attending clinicians. It was only an external review that identified the pathognomonic presentation of intrathecal tranexamic acid.

In South Africa, most specialist-led anesthetic departments in large hospitals have well-established protocols for drug checking during spinal anesthesia. In smaller hospitals, however, spinal anesthesia is typically administered by generalist medical officers who do not work within the structure of an anesthetic department and may not always be aware of the necessity for meticulous drug identification checks. The situation may be similar in many low-middle–income countries, where anesthetics are often administered by a variety of healthcare cadres. Although a lack of specialist oversight may increase the risk for anesthesia-related drug errors, drug errors owing to failure to follow guidance on the safe and secure handling of medicines can occur at any level of hospital, government-run or private, in any part of the world.

Prophylactic use of tranexamic acid at cesarean delivery has been shown to be associated with reduced blood loss >1000ml, but not reduced mortality or severe morbidity. Conversely, increased risk of spinal drug errors associated with routine tranexamic acid administration before cesarean delivery may outweigh any potential benefits. Policies should be informed by a broad consideration of risks and benefits, and future emerging evidence of effectiveness.

Authors recommend the following urgent steps to eliminate the severe and life-threatening consequences of intrathecal administration of tranexamic acid at all hospitals where intravenous tranexamic acid is available:

• 1. Informing anesthetic practitioners and managers of the dangers of intrathecal tranexamic acid using various formats (scientific publications, websites for health practitioners, training programs, government-issued circulars, local health forums for clinicians or health managers, etc.) through various channels, including:

  • World Health Organization
  • National regulatory authorities
  • Pharmaceutical services managers
  • Healthcare training institutions
  • Professional societies
  • Outreach and regional clinicians
  • National or regional clinical guideline documents

  2. Drawing up local risk management strategies and protocols for hospital health practitioners and managers related to the use of tranexamic acid, aimed at minimizing the risk of inadvertent intrathecal administration and enhancing patient safety:

  3. Tranexamic acid must always be stored separately from anesthetic drugs used in the operating room, in a secure container away from the anesthetic drugs trolley.

  4. Tranexamic acid must never be put on the spinal anesthetic trolley that is set up in preparation for administering a spinal anesthetic.

  5. Anesthetic practitioners need to carefully read the label each time before a drug for spinal anesthesia is drawn up, rather than relying on visual recognition or location of the drug ampoules.

  6. If the hospital has a look-alike, sound-alike (LASA) list of medications, tranexamic acid must be added and personnel informed accordingly.

  1.Implementing the following protocols:

  Effective implementation of the strategies and protocols above across all hospitals in a region will require oversight with regular communication and audit of practice by a regional clinical or administrative supervisor.

  For countries where tranexamic acid is being introduced for use in obstetrics for the first time, it is important that the introduction incorporates information about the risk and consequences of inadvertent intrathecal administration and recommendations regarding protocols to minimize risk of the drug error occurring.

  Creative solutions are needed to ensure access for women with PPH to life-saving therapy with tranexamic acid while guarding against the risks of mortality from drug administration errors. Regulatory bodies, suppliers, and manufacturers also have an important role in resolving this problem, for example by ensuring that tranexamic acid drug ampoules carry clear warning labels about the correct route of administration. A coordinated international effort is required to prevent inadvertent intrathecal tranexamic acid administration.

  Source: Moran NF, Bishop DG, Fawcus S, Morris E, Shakur-Still H, Devall AJ, et al. Tranexamic acid at cesarean delivery: drug-error deaths. BJOG. 2023;130(1):114–117.

  https://doi. org/10.1111/1471-0528.17292