Journal Club Podcast #35: May 2017
After a brief interlude where I shamelessly self-promote my new novel, I talk about the risks of delayed bleeding in head injury patients on warfarin...
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Article 1: Menditto VG, Lucci M, Polonara S, et al. Management of minor head injury in patients receiving oral anticoagulant therapy: a prospective study of a 24-hour observation protocol. Ann Emerg Med 2012;59:451-455. Answer Key.
Article 2: Swap C, Sidell M, Ogaz R, Sharp A. Risk of Delayed Intracerebral Hemorrhage in Anticoagulated Patients after Minor Head Trauma: The Role of Repeat Cranial Computed Tomography. Perm J. 2016 spring;20(2):14-6. Answer Key.
Article 3: Chauny JM, Marquis M, Bernard F, Williamson D, Albert M, Laroche M, Daoust R. Risk of Delayed Intracranial Hemorrhage in Anticoagulated Patients with Mild Traumatic Brain Injury: Systematic Review and Meta-Analysis. J Emerg Med. 2016 Nov;51(5):519-528. Answer Key.
Article 4: Nishijima DK, Offerman SR, Ballard DW, et al. Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and pre-injury warfarin or clopidogrel use. Ann Emerg Med2012;59:460-468. Answer Key.
You are working a moonlighting shift at a local level II trauma center when you meet Mr. X, a 68 year old gentleman with a history of atrial fibrillation, for which he takes diltiazem for rate control and warfarin for anticoagulation. He sees his primary care physician on a regular basis and has his international normalized ratio (INR) checked once a week. It has been between 2.0 and 3.0 consistently for the last 6 months. This morning, while walking his dog, a rare crossbreed known as a great doodle (a cross between a great Dane and a poodle), he was tripped up by the leash and fell forward, striking his forehead on the concrete. He suffered no loss of consciousness, has a mild headache, and has had no nausea or vomiting. His wife states that he has had no altered mental status since the fall.
On exam he has a GCS of 15, a superficial abrasion to his forehead with a small 4 cm hematoma, no cervical spine pain or tenderness, and a normal neurologic examination. His INR today is 3.2. Being an astute reader of the literature, you remember that the studies on the Canadian Head CT rules excluded patients on anticoagulation, and proceed to order a head CT, which is read as normal by the attending radiologist (not a neuroradiologist).
After updating the patient’s tetanus booster you discharge him home in the care of his wife. That night after your shift, you begin to worry about your patient and his risk of delayed intracranial hemorrhage given his anticoagulant use. You also wonder if his risk would be higher if he were on one of the novel anticoagulants (rivaroxaban, apixaban, etc). Unable to sleep, you head online and begin to search the literature for answers.
Population: Patients on anticoagulation therapy suffering minor head injury
Intervention: Observation and/or repeat CT scan of the head CT
Comparison: Discharge after normal initial head CT
Outcome: Risk of delayed intracranial hemorrhage leading to a change in management
A previous journal club covering delayed intracranial bleeding in the setting of anticoagulation was conducted in 2012 (http://emed.wustl.edu/Journal-Club/Archive/August-2012). The online archive was searched and two of the articles were chosen for inclusion. PubMed was searched using the terms anticoagulation AND “delayed intracranial hemorrhage”, resulting in 7 articles (http://tinyurl.com/y9yjn3go). Among these, a systematic review and meta-analysis was chosen as well as one of the articles included in the systematic review.
Traumatic brain injury results in just over 1.3 million emergency department (ED) visits, 275,000 hospitalizations, and 52,000 deaths annually in the United States alone, with an increase in the combined rate of ED visits, hospitalization, and death from 521 per 100,000 in 2001 to 823.7 per 100,000 in 2010 (CDC TBI Report). In elderly patients suffering a fall, long-term anticoagulation has been shown to increase not only the incidence of intracranial hemorrhage (ICH) compared to those not on anticoagulation (8.0% vs. 5.3%, p < 0.0001), but to also increase mortality in those with ICH (21.9% vs. 15.2%, p = 0.04) (Pieracci 2007). Additionally, the use of warfarin prior to blunt head trauma has been shown to increase mortality compared to those not taking anticoagulants, with an odds ratio of 2.008 (95% CI 1.634-2.467) (Batchelor 2012). Unfortunately, the rate of pre-injury warfarin use has been increasing in trauma patients in the US, from 2.3% in 2002 to 4.0% in 2006 (P < .001); in patients older than 65 years, use increased from 7.3% in 2002 to 12.8% in 2006 (P < .001) (Dossett 2011).
Given the increasing number of head injury patients seen in the ED, and the increase in concomitant anticoagulant use, the clinical dilemmas surrounding these patients have become more and more relevant. Studies in patients taking warfarin who suffer minor head injury have shown incidences of ICH ranging from 6.2%-29% (Li 2001, Gittleman 2005, Brewer 2011), leading some authors to conclude that most, if not all, such patients should undergo routine cranial CT scanning on presentation (Brewer 2011, Cohen 2006, Fabbri 2004). One important question surrounds the prognostic implications of a normal cranial CT in head injury patients on anticoagulant therapy. While some European guidelines suggest that all anticoagulated patients with head injury should be admitted for a period of routine observation (Vos 2002, Ingebrigtsen 2000), these recommendations are not based on studies of the prevalence of delayed ICH.
In the three primary studies reviewed, the incidence of delayed ICH following normal CT scan in patients taking warfarin ranged from 0.6% to 6%; the meta-analysis revealed a pooled risk of 0.6%. However, if a diagnosed ICH has no affect on the patient’s outcome or treatment, then it would be considered a surrogate outcome, which is often “used as a substitute for a clinically meaningful endpoint that measures directly how a patient feels, functions or survives (Thomas 1995).” As such outcomes are often found to be clinically insignificant, their use has been questioned in the literature (Guyatt 2011, Fleming 1996), and the incidence of patient important outcomes should be considered instead. In these studies, the majority of patients found to have delayed ICH required no neurosurgical intervention and had no adverse outcome documented. The incidence of death or neurosurgical intervention ranged from 0 to 1.1%, with a pooled incidence of 0.13% in the meta-analysis.
The authors of one of the articles reviewed suggest that “our data support the general effectiveness of the European Federation of Neurological Society’s recommendations for 24-hour observation followed by a repeated head CT scan for anticoagulated patients with a minor head injury” (Menditto 2012). However, this conclusion is based on the incidence of delayed ICH (6%) rather than the incidence of clinically important outcomes (1.1%). In this study, only one patient out of 87 suffered clinically significant delayed ICH. It is mentioned in the study that one patient showed signs of neurologic deterioration, however they do not say if this was the same patient who required neurosurgical intervention. If so, this would suggest that observation alone would suffice to detect any clinically significant delayed ICH.
Additionally, the authors do not perform a cost-effectiveness analysis to support their conclusion. In a subsequent editorial appearing in the same journal, it is suggested that a protocol of 24-hour observation and routine repeat CT scanning would cost an average of just over $1 million per patient saved (Li 2012). The author of the editorial suggests that home observation and phone call follow-up would be more cost-effective, and likely as safe, though this has not been studied.
While the current literature does not support routine hospital observation for 24 hours or repeat cranial CT scans in all anticoagulated patients with head injury, this may be warranted in those at increased risk of delayed bleeding, such as those with supratherapeutic INR levels or concomitant antiplatelet therapy. Further studies are needed to identify these higher risk patients for delayed bleeding to determine appropriate management. Furthermore, as newer anticoagulants enter the market and begin to replace warfarin, such as apixaban, dabigatran, and rivaroxaban, further studies on the risk of delayed hemorrhage may be necessary to determine the best management strategy for patients on these medications.