Delayed Traumatic ICH and Oral Anticoagulants

Washington University Emergency Medicine Journal Club – May 19th, 2022


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 apixaban for anticoagulation. This morning, while walking his dog, a rare crossbreed known as a great yorkie (a cross between a great Dane and a Yorkshire terrier), 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. 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 are aware of a prior journal club that found a low risk of delayed bleed with warfarin use, but you wonder if the results apply to patients taking Xa inhibitors and direct thrombin inhibitors. Unable to sleep, you head online and begin to search the literature for answers. 

PICO Question

Not applicable for this review

Search Strategy

Articles were selected by the Critical Care attending and his residents. No formal search
strategy was performed.

Article 1: Puzio TJ, Murphy PB, Kregel HR, Ellis RC, Holder T, Wandling MW, Wade CE, Kao LS, McNutt MK, Harvin JA. Delayed Intracranial Hemorrhage after Blunt Head Trauma while on Direct Oral Anticoagulant: Systematic Review and Meta-Analysis. J Am Coll Surg. 2021 Jun;232(6):1007-1016.e5. doi: 10.1016/j.jamcollsurg.2021.02.016. Epub 2021 Mar 22. PMID: 33766725; PMCID: PMC8722268. Answer Key

Article 2: Mourad M, Senay A, Kharbutli B. The utility of a second head CT scan after a negative initial CT scan in head trauma patients on new direct oral anticoagulants (DOACs). Injury. 2021 Sep;52(9):2571-2575. doi: 10.1016/j.injury.2021.05.039. Epub 2021 Jun 1. PMID: 34130854. Answer Key

Article 3: Turcato G, Cipriano A, Zaboli A, Park N, Riccardi A, Santini M, Lerza R, Ricci G, Bonora A, Ghiadoni L. Risk of delayed intracranial haemorrhage after an initial negative CT in patients on DOACs with mild traumatic brain injury. Am J Emerg Med. 2022 Mar;53:185-189. doi: 10.1016/j.ajem.2022.01.018. Epub 2022 Jan 15. PMID: 35063890. Answer Key

Article 4: Cohan CM, Beattie G, Bowman JA, Galante JM, Kwok AM, Dirks RC, Kornblith LZ, Plevin R, Browder TD, Victorino GP. Repeat computed tomography head scan is not indicated in trauma patients taking novel anticoagulation: A multicenter study. J Trauma Acute Care Surg. 2020 Aug;89(2):301-310. doi: 10.1097/TA.0000000000002760. PMID: 32332255. Answer Key

Bottom Line

In this review we sought to understand some of the factors influencing outcomes in out of hospital cardiac arrest (OHCA), including hyperoxia and the now controversial use of epinephrine and other vasopressors, and to evaluate the association between duration of CPR and potential for survival.

Oxygen Administration

Consistent with prior reports demonstrating poor outcomes associated with hyperoxia for stroke and sepsis, we reviewed a retrospective study that demonstrated a decreased odds of having a favorable neurologic outcome at 6 months with increasing cumulative PaOlevels in the 24 hours following cardiac arrest. After adjusting for known confounders, increasing 24-hour cumulative PaO2 cutoffs were associated with increasing odds ratios for poor neurologic outcome, achieving statistical significance at cutoffs of 200 (OR 1.659, 95% CI 1.194-2.305), 250 (OR 2.082, 95% CI 1.204–3.600), and 300 mmHg (OR 3.969, 95% CI 1.450-10.862). This study was limited by its retrospective nature necessitating logistic regression to account for known confounders, but no means of accounting for unknown confounders. Despite its limitations, and in the context of previous evidence, it seems prudent to titrate supplemental oxygen downward following cardiac arrest to maintain normal oxygen saturation and PaO2 levels.

CPR Duration

Goto et al undertook a study in Japan to determine the duration of prehospital CPR that would allow cessation of resuscitative efforts without sacrificing survivorship or favorable neurologic outcomes. Using data from a large, nationwide database, they found (not surprisingly) an inverse relationship between CPR duration and good outcomes, such that every additional minute of CPR time was associated with  an decreased odds ratio for 1-month survival of 0.95 (95% CI: 0.95–0.96) and a decreased OR for a favorable 1-month neurological outcome of 0.95 (95% CI: 0.94–0.95). To achieve a cumulative proportion of >99% of favorable neurologic outcomes at one month, CPR durations of 35 minutes for all patients, 35 minutes for PEA and ventricular fibrillation/pulseless ventricular tachycardia, and 42 minutes for asystole were required. While interesting, it remains unclear whether these time-frames should or could be used to terminate resuscitative efforts in prehospital cardiac arrest, and care should be taken before generalizing these results given issues with external validity.


Given controversies with the use of epinephrine in cardiac arrest, two papers regarding its use were reviewed. The first (Tanaka 2016) looked specifically at the timing of epinephrine administration and effects on outcomes. This retrospective observational study used data from a large, nationwide Japanese database of OHCA cases, and found that those patients who received epinephrine were more likely to have return of spontaneous circulation (ROSC) than those who did not (RR 1.92, 95% CI 1.85 to 1.99) but were less likely to have a favorable neurologic outcome at one month (RR 0.56, 95% CI 0.52 to 0.61). When epinephrine was given, there was a notable decline in rates of ROSC and favorable neurologic outcome with increasing time to administration of the first dose.

Based on prior conflicting reports, and specifically given the recent publication of the PARAMEDIC-2 trial (a large randomized controlled trial suggesting epinephrine did not improve rates of favorable neurologic outcome in OHCA), the International Liaison Committee on Resuscitation (ILCOR) commissioned a systematic review and meta-analysis looking at the use of vasopressors during cardiac arrest. This review found an increased rate of ROSC with epinephrine compared to placebo, but no benefit with regards to survival to hospital discharge with a favorable neurologic outcome (RR 1.21, 95% CI 0.90-1.62) or favorable neurologic outcome at 3 months (RR 1.30, 95% CI 0.94-1.80). Additionally, they found no difference in outcomes comparing vasopressin to epinephrine and no benefit to giving vasopressin in addition to epinephrine.