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It is critical to master the management of the patient with intracerebral hemorrhage (ICH) because hematoma expansion typically occurs in the first few hours after the bleed starts, and hematoma volume is the most important predictor of early deterioration.1 A self-fulfilling prognostic pessimism exists when it comes to ICH, and this pessimism sometimes leads to less-than-optimal care in patients who otherwise might have had a reasonably good outcome if managed aggressively.
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ACEP Now: Vol 37 – No 03 – March 2018Despite the poor prognosis of these patients overall, there is some evidence to suggest that early aggressive medical management may improve outcomes.2 As such, the skill with which you manage your emergency department ICH patients matters. In this golden hour, you have a chance to prevent hematoma expansion, stabilize intracerebral perfusion, and give your patient the best chance of survival with a favorable neurological recovery.
Five major considerations in the medical management of ICH should guide your management: blood pressure (BP), coagulation, glucose, temperature, and intracranial pressure (ICP) control.
Blood Pressure Management
For those ICH patients with Glasgow Coma Scale (GCS) scores >7, the current recommendation to lower BP to 140/80 is unlikely to be harmful but may be minimally beneficial. However, two recent trials have failed to definitively show benefit. The INTERACT2 trial was a randomized, controlled trial (RCT) of 2,839 patients with spontaneous ICH and elevated systolic BP who were randomized to intensive treatment (<140) versus guideline-recommended therapy (<180).
Outcomes were modified Rankin score of 3 to 6 (death and major disability) at 90 days. The researchers found no significant difference in primary outcomes.3 The ATACH-II RCT compared a lower systolic BP target of 110 to 139 mm Hg with a standard target of 140 to 179 in 1,000 patients using IV labetalol, diltiazem, or urapidil. Patients were eligible if they had at least one episode of systolic BP >180 mmHg between symptom onset and 4.5 hours. The trial was stopped early for futility, with no difference in the primary outcome of death or disability (intensive treatment group 38.7 percent versus control 37.7 percent).4 While the target BP in ICH requires more study, there is no question that hypotension should be avoided at all costs in patients with ICH.
Platelet Transfusions
All patients with a platelet count <50,000 in the setting of ICH require platelet transfusion. However, most hematologists and neurosurgeons recommend platelet transfusion for ICH with a platelet count <100,000 despite the lack of evidence for improved outcomes, especially when the patient requires emergency surgery.
For patients with ICH taking antiplatelet agents, the PATCH trial, a RCT in the Netherlands, United Kingdom, and France, randomized 190 patients with supratentorial ICH and a GCS >8 who had received antiplatelet therapy (mostly aspirin alone) within seven days to standard care or care with platelet transfusion.
An ordinal analysis looking at modified Rankin score and death showed an odds ratio of death of 2.05 in the treatment group. More serious adverse events were reported in patients who received platelet transfusion (42 percent) compared with patients who received standard care alone (29 percent). The researchers concluded that platelets were associated with poorer clinical outcomes overall.5 It is important to note that these patients were primarily nonsurgical ICH patients. For patients requiring emergency surgery, most neurosurgeons recommend platelet transfusion for patients taking antiplatelet agents.
Reversal of warfarin: Any patient taking warfarin who presents to the emergency department with ICH should receive IV four-factor prothrombin complex concentrates (PCCs) 1,500 units (Octaplex, Beriplex, or Kcentra) as soon as possible and IV vitamin K 10 mg in 50 mL of normal saline over 10 minutes. Treatment should not be delayed for the international normalized ratio results to come back, as hematoma expansion typically occurs within the first hour in patients taking warfarin.6
Reversal of dabigatran: Idarucizumab is the reversal agent of choice for dabigitran despite the lack of evidence for improved patient outcomes.6 If idarucizumab is not available, consider factor eight inhibitor bypass activity (FEIBA). If FEIBA is not available consider four-factor PCC.
Reversal of Xa inhibitors: For Xa inhibitors (eg, apixaban, rivaroxaban) 4-factor PCC at a dose of 50 IU/kg up to 3,000 units is the reversal agent of choice based on limited evidence. Andexanet alfa is a decoy antigen; it competitively binds rivaroxaban and apixaban and is given as an ongoing infusion. The evidence is not convincing for its effectiveness.6
Glucose Control
Hyperglycemia is common in patients presenting with ICH and is associated with poor outcomes.7 The optimal glucose level and the best hyperglycemia management strategy remain undecided. However, both hypoglycemia (<70 mg/dL) and hyperglycemia (>180 mg/dL) should be avoided. A study suggested improved clinical outcomes with tight control of blood sugar to the range of 80 to 110 mg, but this was found to cause occasional hypoglycemia resulting in increased mortality.8
Temperature Control in ICH
So-called “brain blood fever” is common in ICH, with 30 to 50 percent of patients developing fever. The presence of intraventricular hemorrhage is the main risk factor for fever. Fever is independently associated with poor outcomes. While there are no available data from RCTs addressing the role of induced normothermia after ICH, current recommendations are to cool febrile ICH patients to a core temperature below 37.5 to 38 °C.9
Management of Elevated ICP
Management of elevated ICP starts with meticulous airway management for those patients whom you deem at risk for aspiration. Keep the head of the bed elevated at least 20 degrees to prevent spikes in ICP. Titrate systolic BP to 140 to 160, preferably with an arterial line in place. Consider fentanyl 3–5 mcg/kg pretreatment three minutes before intubation, but beware of the possibility of apnea and provide appropriate analgesia and sedation postintubation. Avoid hypoxemia and hypotension at all costs in ICH. Hyperventilation to a PCO2 of 30 to 35 is only recommended as a temporary bridge to definitive surgical management in those patients who are actively coning.
Although not routinely indicated, consider hypertonic saline or mannitol based on ICP monitoring, point-of-care ultrasound optic nerve sheath diameter >6 mm, or clear signs of elevated ICP on brain imaging (not simply for low GCS).10,11 While there is no RCT evidence that hypertonic saline (3% 250 mL over 10 minutes) is superior to mannitol for controlling elevated ICP, it may be preferred because there are fewer concerns with sodium derangement and changes in hemodynamics. If you use mannitol, it is advisable to match urinary losses with normal saline administration to avoid hypotension.
While no single medical treatment has been shown to improve outcomes in ICH, if we avoid extremes of blood pressure, temperature, and glucose while minimizing spikes in ICP and rapidly reversing anticoagulants in the emergency department, we will give our ICH patients the greatest chance of a neurologically intact survival.
Thanks to Walter Himmel and Scott Weingart for their contributions to the EM Cases podcast that inspired this article.
References
- Specogna AV, Turin TC, Patten SB, et al. Factors associated with early deterioration after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis. PLoS One. 2014;9(5):e96743.
- de Oliveira Manoel AL, Goffi A, Zampieri FG, et al. The critical care management of spontaneous intracranial hemorrhage: a contemporary review. Crit Care. 2016;20:272.
- Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355-2365.
- Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med. 2016;375(11):1033-1043.
- Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelt therapy (PATCH): a randomised, open-label, phase 3 trial. Lancet. 2016;387(10038):2605-2613.
- Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016;24(1):6-46.
- Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology. 2003;61(10):1351-1356.
- NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283-1297.
- Hemphill JC 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(7):2032-2060.
- Stevens RD, Shoykhet M, Cadena R. Emergency neurological life support: intracranial hypertension and herniation. Neurocrit Care. 2015;23(Suppl 2):S76-82.
- Raffiz M, Abdullah JM. Optic nerve sheath diameter measurement: a means of detecting raised ICP in adult traumatic and non-traumatic neurosurgical patients. Am J Emerg Med. 2017;35(1):150-153.
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