Critical Care, Critical Care Alert, PGY1

Critical Care Alert: Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

A 57-year-old male with a history of hypertension and diabetes develops a severe headache and nausea. He becomes unresponsive shortly thereafter. EMS is called by his wife. On initial presentation to the ED vital signs are: BP 220/120, HR 110, RR 8, SpO2 95%. Pupils are 3 mm fixed bilaterally with a GCS of 3. Patient is intubated for airway protection and head CT is suggestive of large thalamic hemorrhage. How would you manage his hypertension?

Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med. 2016 Sep 15;375(11):1033-43.

To compare rate of death or disability in hypertensive patients with intracerebral hemorrhage (ICH) treated to a target systolic blood pressure of 110-139 mm Hg versus standard reduction to a target of 140-179 mm Hg.

Elevated blood pressure (BP) in acute ICH is commonly associated with greater hematoma expansion and is thought to contribute to neurological deterioration and death. Limited data are available to guide physicians in choosing a target systolic BP (SBP) when treating acute hypertension in patients with intracerebral hemorrhage. Based on prior available studies, the 2015 AHA/ASA recommendation suggests acute lowering of SBP to 140 mmHg for patients presenting with SBP between 150-220 mmHg without contraindication to acute BP treatment. The ATACH-2 trial was designed to investigate whether there is a benefit in further lowering of blood pressure.

Randomized, multicenter, international, two-groups, open-label trial to determine the relative efficacy of intensive (target 110-130 mmHg) versus standard (140-179 mmHg) antihypertensive treatment initiated within 4.5 hours after symptom onset and continued for the next 24 hours in patients with spontaneous supratentorial ICH. This included 110 sites in the US, Japan, China, Taiwan, South Korea, and Germany. 500 patients were assigned to intensive treatment group and 500 to the standard treatment group.

Inclusion criteria: 18 years of age or older with GCS of 5 or more, measurement of intraparenchymal hematoma of less than 60 cm3 on initial CT scan, at least one reading of SBP of 180 mmHg or more between symptom onset and the initiation of IV antihypertensive, randomization within 4.5 hours after symptom onset

Exclusion criteria: Systolic BP reduced to less than 140 mmHg before randomization

Intervention: Nicardipine was used as primary anti-hypertensive medication to reduce and maintain minimum SBP in the range of 140-179 mmHg in standard-treatment group and in the range of 110-139 mmHg in the intensive-treatment group throughout a period of 24 hours. Initial dose of nicardipine was 5 mg per hour, which was then increased by 2.5 mg per hour q15 min as needed, with a max of 15 mg per hour. A prespecified second agent, intravenous labetalol, was used if BP was higher than target despite max dose of nicardipine. In countries where labetalol was not available, intravenous diltiazem or urapidil was used.

Primary Outcome: Moderately severe or severe disability (modified Rankin scale score 4-6) or death at 3 months

Secondary Outcome: EQ-5D utility index visual analog scale (measurement of health-related quality of life) at 3 months, proportion of participants with expansion of 33% or more in volume of hematoma on CT scan obtained 24 hours after randomization

Key Results
The primary outcome of death or disability was observed in 186 participants (38.7%) in the intensive-treatment group and 181 participants (37.7%) in the standard-treatment group with a relative risk of 1.04 (95% confidence interval [CI], 0.85 to 1.27), with adjustment for age, initial GCS score, and presence or absence of intraventricular hemorrhage. There was NO significant difference between group in terms of Rankin scale score at 3 months. Rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group.

No significant difference between groups in the rate of death at 3 months or in neurologic deterioration at 24 hours after randomization. The trial was discontinued for futility before target enrollment of 1,280 participants were reached.

Results of this study do not support the notion that acute reduction to a target SBP of 110-139 mmHg in patients with ICH is more effective in improving functional outcome than a reduction target SBP of 140-179 mmHg. In addition, the rate of renal adverse events was higher in the intensive-treatment group than in the standard treatment group.