Inadvertent Intrathecal Administration Research Articles

Tranexamic Acid at Cesarean Delivery: Drug-error Deaths

(Am J Obstet Gynecol. 2023;228:1–4) Tranexamic acid plays an important role in reducing bleeding experienced during postpartum hemorrhage. It is recommended by the World Health Organization that tranexamic acid is administered intravenously, over 10 minutes, within 3 hours of delivery to treat postpartum hemorrhage. However, tranexamic acid, although helpful in cases of postpartum hemorrhage, has caused other problems to arise. It has been found that tranexamic acid is toxic when administered intrathecally (IT). Tranexamic acid has components that are known to lead to neuronal excitation when mistakenly administered in the intrathecal space. This most often leads to generalized convulsions and malignant arrhythmias. This has been occurring more frequently secondary to tranexamic acid being stored in labor and delivery operating rooms on anesthetic drug carts for easy access for hemorrhage during cesarean delivery. Both tranexamic acid and the drugs used for spinal anesthesia are stored in look-alike glass vials making this risk even more likely. A review published in 2019 reported 21 cases of inadvertent intrathecal administration of tranexamic acid, 20 of these cases were life-threatening with ten resulting in patient deaths. The accidental administration of tranexamic acid intrathecally most likely occurs more often than it has been reported. The mistake of replacing spinal anesthesia drugs with tranexamic acid most commonly occurs in small hospitals and low-middle-income countries.

Hidden risk of gadolinium-based contrast agents during interventional pain medicine procedures: a retrospective chart review

IntroductionEpidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and...

Tranexamic acid at cesarean delivery: Drug-error deaths.

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. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. 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.

Tranexamic acid at cesarean delivery: drug-error deaths.

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. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. 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.

Tranexamic acid at cesarean delivery: drug-error deaths

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. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. 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.

Tranexamic acid at cesarean delivery: drug-error deaths

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. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%.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.

Labeling Changes for Vinca Alkaloid Chemotherapies.

The labeling for vinca alkaloid chemotherapy drugs is being revised to remove instructions for their administration with use of a syringe. This revision is in response to inadvertent intrathecal administration of vinca alkaloids, which is normally fatal.

Intrathecal tranexamic acid during spinal anaesthesia for caesarean delivery: A lethal drug error

The National Committee on Confidential Enquiries into Maternal Deaths recently received notification of a death in South Africa caused by inadvertent intrathecal administration of tranexamic acid (TXA). TXA is increasingly used during caesarean delivery following updated recommendations from the World Health Organization in 2017. However, its greater availability has led to an international rise in drug errors during obstetric spinal anaesthesia. This case highlights a growing clinical risk, of which all operating theatre staff should be aware. Review of existing operating theatre drug handling practices is required in order to decrease this risk. Recommendations are made that aim to minimise drug errors associated with the use of this potentially life-saving intervention.

Fatal gadolinium-induced encephalopathy following accidental intrathecal administration: a case report and a comprehensive evidence-based review.

Gadolinium-based contrast agents (GBCAs) have been suggested as off-label alternatives to iodine-based contrast agents for fluoroscopic imaging during interventional pain procedures. We report a case of accidental intrathecal administration of a GBCA during a neuraxial interventional pain procedure leading to acute gadolinium neurotoxicity, which resulted in encephalopathy and ultimately death. To our knowledge, it is the first published case of fatal intrathecal gadolinium-induced encephalopathy and the first published case of intrathecal gadoteridol causing serious neurologic complications. In addition, the case presented here is placed in context with an associated comprehensive, evidence-based review of the use of gadolinium in interventional pain procedures, addressing gadolinium chemistry and pharmacologic properties, neurotoxicity and radiology. Physicians must be aware that gadolinium poses a significant risk of acute neurotoxicity even in small doses. Until further safety research is performed, GBCAs should not be considered a safe alternative for use in neuraxial interventional spine procedures when there is a risk of inadvertent intrathecal administration.

Inadvertent Intrathecal Vincristine Administration with Widespread Axonal Injury Demonstrated by Amyloid Precursor Protein Immunohistochemistry

Vincristine is a Vinca alkaloid chemotherapeutic agent used to treat hematologic and some solid organ neoplasms. As a microtubule inhibitor, an unfortunate side effect of this drug is disruption of axonal transport. Thus, the drug is intended for intravenous use only. We report a 59-year-old man with diffuse large B-cell lymphoma who inadvertently received intrathecal vincristine. The patient experienced progressive neurologic decline despite attempts at cerebrospinal fluid lavage with fresh frozen plasma and died five days after the incident. Grossly, there was evidence of prior shunt placement, the brain was mildly swollen, and the white matter appeared congested. Histological study revealed pallor of the centrum semiovale, focal perivascular hemorrhages, and widespread axonal spheroids that were demonstrated by immunohistochemical study for amyloid precursor protein (APP). There was subependymal spongiosis and focal hydropic-like change of the ependyma. Proximal axon segments of anterior horn neurons showed many APP-reactive spheroids as they exited the spinal cord. Anterior spinal nerve roots also contained APP-positive swellings. No significant pathologic changes were identified in the gray matter. In particular, there was no Purkinje cell loss. No evidence of residual lymphoma was identified. This case illustrates diffuse axonal injury that was caused by toxic disruption of axonal transport and was clearly demonstrated by immunohistochemistry for APP. This case emphasizes the need for continued awareness of this preventable medical error.

Introduction of vincristine mini-bags and an assessment of the subsequent risk of extravasation.

Numerous international organisations have advocated the preparation of vincristine in small volume intravenous bags in order to eliminate inadvertent intrathecal administration. However, the risk of extravasation is a significant deterrent, and adoption of this practice has been variable and only hesitantly accepted in the clinical setting. We carried out a study with the aims of establishing the incidence of reported extravasation of vincristine administration to paediatric and adult patients in mini-bags; here we describe motivating factors and barriers faced by clinical staff. The secondary aim was to support the need for change and implementation of the international recommendations. Chemotherapy-certified nurses completed a survey spanning August 2009 to August 2011, to ascertain the incidence of extravasation associated with the administration of vincristine in mini-bags. This period captured 421 occasions of vincristine administration in 25-ml or 50-ml mini-bags (in 0.9% sodium chloride). The median age of patients was 13 years (range 2.5 months to 99 years). Vincristine was administered through peripheral lines (26.4%), portacath (52.0%), PICC line (15.9%) and Hickman line (5.7%). The majority of infusions were over at least 10 minutes (50.1%). There were no cases of extravasation reported. The administration of vincristine in small volume intravenous bags was safe, practical, and feasible in all patient groups. The successful implementation of the international recommendations for vincristine administration in mini-bags to eliminate potential inadvertent intrathecal administration was dependent on stakeholder buy-in.

Identifying systems failures in the pathway to a catastrophic event: an analysis of national incident report data relating to vinca alkaloids

BackgroundCatastrophic errors in healthcare are rare, yet the consequences are so serious that where possible, special procedures are put in place to prevent them. As systems become safer, it becomes...

Magnetic Resonance Characteristics and Susceptibility Weighted Imaging of the Brain in Gadolinium Encephalopathy

To report the brain imaging features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors.

Status epilepticus attributed to inadvertent intrathecal injection of cefazolin during myelography

To describe a case of status epilepticus believed to be a consequence of inadvertent intrathecal administration of cefazolin in a dog undergoing a myelogram. A 4-year-old, 6.5 kg, male neutered Dachshund was referred for evaluation of an acute onset hind limb paraparesis. While performing a lumbar myelogram, cefazolin was inadvertently injected into the ventral subarachnoid space. Subsequent refractory seizure activity was attributed to the epileptogenic effects of intrathecally administered cefazolin. Supportive therapy led to eventual complete recovery. Although epileptogenic effects of intrathecally administered cefazolin are well documented in the human and experimental animal model literature, to the authors' knowledge this has not been characterized in the veterinary literature. This case highlights the need to be diligent and mindful when one administers medications, and describes the management of a dog adversely affected as a consequence of a medical error.

Accidental Intrathecal Administration of Vincristine in Pediatric Patients

Vincristine has been in clinical use for over 50 years and is indicated in the treatment of a wide range of adult and pediatric malignancies, most commonly in combination therapy. Dose-limiting toxicities of vincristine arise primarily in the peripheral nervous system with central nervous system toxicity generally not observed with intravenous therapy due to poor penetration of the blood brain barrier. Unintentional administration of vincristine directly into the cerebrospinal fluid (CSF) produces profound neurotoxicity. Since the first report in 1968 there have been numerous other cases with 31 (18 in children) of these published in the literature with 25 (15 in children) resulting in death. Many other cases are believed to have occurred but have not been officially reported. Fatalities appeared due to a progressive ascending myeloencephalopathy. Early recognition and immediate treatment with CSF drainage and intrathecal exchange appears to be the only intervention that has improved patient survival. Guidelines for the prevention of this horrific medication error have been proposed. All errors involving the administration of a vinca alkaloid into the CSF over the past 45 years have occurred when the drug has been prepared in a syringe. The most effective method currently available for preventing this tragic and invariably fatal event from ever happening is to abolish the syringe as a method of vincrisine administration. This method must be replaced by administration via a small-volume intravenous bag for all patients. Concerns regarding an increased risk of extravasation with the use of mini-bags, particularly in the pediatric population, are unfounded and should not be a deterrent to implementing this strategy. The consequences of inadvertent intrathecal administration of vincristine are overwhelming. The optimum strategy for managing this problem is by developing effective methods of prevention and incorporating these proposals into pediatric oncology centers internationally.

Ascending tonic‐clonic seizure syndrome in a dog following inadvertent intrathecal use of ionic contrast agent

To describe the successful management of ascending tonic-clonic seizure syndrome in a dog after inadvertent intrathecal administration of ionic contrast material. A 7-year-old, 5.9 kg, male castrated Miniature Pinscher inadvertently received intrathecal ionic contrast material during a myelogram to investigate cervical pain. Ascending tonic-clonic muscle spasms quickly progressed to generalized seizure activity that was resistant to anticonvulsant medications. The dog developed complete respiratory arrest, which necessitated mechanical ventilatory support for 26 hours. Pneumonia developed and was treated successfully. After resolution of seizure activity and resumption of voluntary respiration, the dog remained tetraparetic for 16 days and was not able to walk on his own for 20 days post contrast injection. Despite a prolonged recovery, the patient survived and recovered normal neurologic function. Intrathecal administration of ionic contrast material resulting in ascending tonic-clonic seizure syndrome is rarely reported in the human and veterinary literature. No previous veterinary report has described successful treatment after prolonged respiratory arrest. In previous veterinary reports, patients recovered complete neurologic function within hours to days in contrast to this report in which the patient was tetraparetic for 16 days. This report demonstrates complete recovery from intrathecal ionic contrast administration is possible despite a high dose of contrast and a prolonged recovery.

Deaths reported from the accidental intrathecal administration of bortezomib

Medication errors due to the inadvertent intrathecal administration of vincristine and other antineoplastic agents continue to occur despite the development of preventative strategies. Three fatalities due to bortezomib being accidentally given intrathecally instead of by the intended intravenous route have recently been reported by the European Medicines Agency. The most effective method for preventing accidental intrathecal administration is to eliminate the syringe as a means of administrating neurotoxic agents and prepare them in a small volume minibag. However due to a lack of stability data for bortezomib in a minibag and the increasing use of bortezomib via the subcutaneous route necessitates the continued preparation of bortezomib in a syringe. A number of recommendations aimed at preventing the possibility of accidental intrathecal administration of bortezomib are made. These need to be incorporated into standard practice internationally and pharmacists must take the lead to ensure this occurs as a matter of urgency.

Early Encephalic Toxicity after Inadvertent Intrathecal Injection of Low Osmolar Contrast Medium

Only nonionic contrast media are allowed for intrathecal use because of their lower neurotoxicity. In case of inadvertent intrathecal administration of an ionic contrast medium, the typical following syndrome is called ascending tonic clonic seizure syndrome. We describe the case of a 61-year-old woman with low back pain who underwent myelography. Ioxaglate, a water-soluble ionic low osmolar contrast medium was accidentally injected intrathecally. She first presented encephalic signs of neurotoxicity, followed by opisthotonic spasms and respiratory distress. In our case, ioxaglate is a low osmolar agent, leading to early encephalic toxicity (preceding medullary signs), because of its cephalic migration. The patient was successfully treated by sedation, anticonvulsant therapy and fluid hydration. Intrathecal administration of an ionic contrast medium is clearly contraindicated. In case of inadvertent injection of a low osmolar product, encephalic signs are seen first.

Vincristine-induced central neurotoxicity in a collie homozygous for the ABCB1Δ mutation

A six-year-old, neutered, female collie was presented to an oncology specialty service after developing tetraparesis and self-mutilation that progressively worsened while receiving chemotherapy for lymphoma. Neurologic examination revealed ataxia, paresis and diminished conscious proprioception in all limbs with entire spinal reflexes. Magnetic resonance imaging of the brain and spinal cord was normal. Electromyography of the limbs ruled out a vincristine-induced peripheral neuropathy. Cerebrospinal fluid analysis and cerebrospinal fluid and serum testing for Neospora and Toxoplasma were normal. Results of MDR1 genotyping revealed that the dog was homozygous for the ABCB1-1Δ (MDR1) mutation. This clinical presentation strongly resembled the effects seen from inadvertent intrathecal administration of vincristine in humans. Dogs that are homozygous for the ABCB1-1Δ (MDR1) mutation should not receive standard dosages of chemotherapy drugs known to be eliminated by P-glycoprotein, the gene product of ABCB1. Testing for this mutation is strongly recommended before chemotherapy initiation for at-risk breeds.

Inadvertent intrathecal administration of vincristine: Has anything changed?

Inadvertent intrathecal administration of vincristine: Has anything changed?