Roberts, James R. MD
Individuals with intracranial hemorrhage (ICH) are common in every emergency department. A devastating neurological process, ICH presents an ever-evolving challenge to emergency physicians. The lay public is relatively clueless about the devastating effects of brain hemorrhage, and often thinks highly skilled physicians can return patients with hemorrhagic stroke back to normal, especially if everything is done correctly. While this might be somewhat true for a few fortunate survivors, brains continue to bleed, and a dead brain usually stays dead.
This large ICH is li...Image Tools
Fortunately, rehabilitation of other areas of the brain and the body's remarkable reparative processes offer some respite from certain paralysis or a long-term vegetative state. What doctors can do to help the acutely bleeding brain or enhance recovery is still quite a mystery.
This column begins a series on the ED approach to stroke by focusing on the hemorrhagic stroke victim's blood pressure. Brains have been bleeding for centuries, but medical science is still confused by basic issues. The most advantageous clinical approach is befuddled by theory, conflicting or lacking data, nonintuitive clinical outcomes, unwarranted pessimism, and unbridled optimism. Even the most basic interventions lack support by rigorous data. One would think we know exactly what to do by now, and we should have the pathophysiology well in hand. Unfortunately not.
The peccadilloes of blood pressure bewilder even the most erudite c-linician. Currently, we have only guidelines, a pronouncement that we really don't know what to do, but some choices make sense (at least for now). Guidelines are usually only a consensus of opinion, generally based on an interpretation of less-than-pristine data and often combined with a boatload of guessing. Today's dogma can be tomorrow's heresy. The recent guidelines for the control of blood pressure in ICH exemplifies typical attempts to shed light on a dark subject.
Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association
Morgenstern LB, et al
You may have missed this landmark article, even though it has been the subject of many reviews and medical talk shows. These guidelines contain a plethora of recommendations on spontaneous ICH, but I will focus on those dealing with blood pressure control. A more cogent analysis can be heard on EM:RAP (www.emrap.us; October 2010.)
Severe hypertension is a frequent if not omnipresent hallmark of ICH. It is a cause and proximate effect of a brain bleed, and usually produces more severe hypertension than an ischemic stroke. Hypertension can be a secondary response to adrenergic responses from the sympathetic nervous system, activation of the renin-angiotensin axis, or glucocorticoid effect. Hypertension is likely the body's paramount response to unwanted blood deep within the brain. Increased intracranial pressure also contributes to rising blood pressure.
There has never been a clear association between uncontrolled hypertension within the first few hours of ICH and the outcome or subsequent expansion in the hematoma's size, but much is made of this theoretical association. In theory (and it seems so logical), hypertension would expand the hematoma, while lowering it would intuitively ameliorate expansion, saving ailing brain. It seems reasonable to conclude that a large hematoma would be more detrimental to a favorable outcome than a small one. One reason to tread gingerly with the manipulation of the blood pressure after a nonhemorrhagic ischemic stroke is that it may be undesirable to lower blood pressure to the relatively underperfused yet still potentially viable part of the brain termed the ischemic penumbra. Unlike ischemic stroke, there does not appear to be a penumbra of hyperprofusion surrounding ICH.
These guidelines from the AHA and ASA appeared only three years after the promulgation of prior guidelines. (Stroke 2007;38:2001.) These organizations concluded that an update was needed because of a few important studies since 2007 evaluating the mechanism of ICH and the safety of lowering blood pressure early. Two studies impressed the AHA and ASA: INTERACT (Lancet Neurol 2008;7:391) and ATACH (Neurocrit Care 2008;8:316), although neither study found a change in patient-oriented outcome.
The INTERACT study randomly offered blood pressure control within six hours of intracranial hemorrhage to only 404 Chinese patients. Intensive IV blood pressure-lowering agents -(“locally available in China”) were given to achieve a systolic blood pressure of about 140 mm Hg within one hour, and were maintained for 24 hours. The comparison group had a systolic blood pressure goal of 180 mm Hg, considered standard management and a recommendation from the earlier guidelines. (Stroke 1999;30:905.) The study had no statistical power to detect a true difference in hematoma growth, but aggressive control of blood pressure “trended” toward a decreased absolute growth of the hematoma from baseline to 24 hours. There were no signs of neurological deterioration or other adverse effects when blood pressure was lowered to a point previously viewed as producing potentially dangerous hypoperfusion. Importantly, however, disability and quality of life between the two groups was not significantly different.
The ATACH trial confirmed the feasibility and possible safety of early and rapid blood pressure-lowering in ICH. This study had only 21 patients in each group (mean arterial pressure [MAP] target either 110-130 mm Hg or below 110 mm Hg). There was no change in hematoma volume or any neurological outcome from aggressive reduction of acute hypertension, even when started in the first few hours of symptoms. Note to the AHA and ASA: Acutely lowering blood pressure might be safe, but it has no measurable effect on hematoma growth, does not decrease the rate of neurological deterioration, and has not been proven to enhance outcome. The knowledge gained from these studies was minimal and not statistically valid, yet updated guidelines were offered. Maybe a bit hasty, but understandable under the circumstances and edict to do something helpful.
It appears blood pressure can be lowered immediately by intensive IV antihypertensive therapy, and it is potentially safe to do so. Of greatest importance, however, specific blood pressure targets and duration of therapy remain unknown.
Despite these machinations, prior recommendations for actual blood pressure targets were not changed in the updated guidelines, although they do say “in patients presenting with a systolic blood pressure of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe.” This was a class IIA recommendation (“the weight of evidence or opinion is in favor of the procedure or treatment”), based on level of evidence B (“data derived from a single grade A study or one or more case controlled studies or studies using a reference standard applied to an unmasked evaluator”). To totally confuse blood pressure control, acute lowering is only considered if there is no evidence of increased intracranial pressure.
While it may be “potentially safe” to lower blood pressure in patients with ICH who have significant hypertension, an improvement in clinical outcomes by doing so remains uncertain.
Comment: A lot of hoopla was made of these new guidelines. Curiously, I could find no authors with FACEP or FAAEM after their names. Apparently, no emergency medicine organization reviewed or affirmed the contents. When read carefully, there are relatively little new data, no real answers, and precious little new science. These guidelines seemed spawned by two studies that did not actually prove anything substantial. I remain confused.
I am particularly stymied by the need to promulgate these and deem them official guidelines of two prestigious medical associations. Such a stance offers fodder for critics of physicians who don't read the guidelines, disagree with them, or read them with rigor and realize that the science is quite weak. There is still waffling by the AHA and ASA that makes life difficult for clinicians, especially EPs who must do something to the patient in front of them.
A further perusal of the recommendations gleans that blood pressure recommendations “may be considered.” The words “may” and “consider” are vague and confusing to me, but the tone of this publication is more of “do it” rather than cogitate. This is clearly a difficult subject to nail down. If only professional societies had the guts to directly address the corner into which they have painted emergency physicians on patient expectations, family satisfaction, and the mindset of our critics.
The final outcome from ICH is dismal, with 30-day mortality rates ranging from 35 percent to 52 percent. About half of the deaths occur within the first two days. Only a small number of patients are functionally independent after ICH, with only 10 percent to 12percent normal or minimally handicapped at 30 days. (Stroke 1991;22:1.) Patients who were previously anticoagulated or taking antiplatelet therapy do even more poorly. Those with a cerebral aneurysm or AV malformation tend to fare better, probably because they are younger with less comorbidity, have warning signs, and are more amenable to high-tech interventions, like coiling. The majority of patients with ICH treated in the ED will be disasters — elderly patients with scads of heinous pre-existing unsolvable medical problems, often anticoagulated, and with significant additional risks for a poor outcome.
Blood Pressure Management in Patients with Acute Stroke: Pathophysiology and Treatment Strategies
Ezzeddine M, et al
Neurosurg Clin N Am
2006;17 Suppl 1:41
This 2006 article is a neurosurgeon's approach to managing hypertension in ICH. As with all other authorities and after copious reviews and summaries, these authors adroitly conclude that the ideal approach to hypertension in ICH is unknown. They repeat the mantra that the majority are hypertensive on admission, with a subsequent natural gradual decline in blood pressure within the first 24 to 48 hours. Hypertension is likely a physiological consequence of brain injury, even the absence of pre-existing hypertension. Persistently elevated blood pressure after ICH is associated with a less favorable outcome, although a cause and effect has not been proven. Of course, very low blood pressure is also associated with increased mortality. Pre-existing hypertension is the most important risk factor for a spontaneous bleed. Long-term antihypertensive therapy reduces the risk of ICH.
Severe hypertension may lead to hematoma expansion, or not, and a bigger clot may predict a poorer neurological outcome. It is unclear and still enigmatic whether acute hypertension is the cause of hematoma enlargement or a manifestation the initial injury worsening. Prior theories suggesting a perihemorrhagic hypoperfusion, ischemia, or ischemic penumbra (as seen with ischemic CVA) have not been proven in ICH, and appear not to be a major issue. These authors reference the 2007 AHA and ASA guidelines that if the systolic pressure is greater than 180 mm Hg or MAP greater than 130 mm Hg, one should consider intervention, aiming at a range of 160/90 mm Hg (MAP 110). I assume that if the blood pressure is 159 or the MAP is 129, the pressure should be left alone. And these only apply in the absence of elevated ICP. How is the EP to know that?
After writing a complete book on the subject, these authors, likely everyone else, conclude that the best strategy for blood pressure in the acute post-ICH period remains unclear. While moderate control of blood pressure is intuitively attractive, possibly limiting hematoma expansion, definitive studies are needed before this is standard of care. If blood pressure control is considered, short-acting IV agents that can be titrated are preferred.
Comment: These neurosurgeons, who actually operate on ICH patients, seem to think that 180/110 mm Hg is acceptable in the immediate post-bleed period. While subsequent studies have demonstrated that lowering the systolic pressure as low as 140 mm Hg systolic may not be harmful, it has not been proven to be beneficial in any subgroup. With due reverence to the capabilities of our neurosurgical colleagues, their clinical expertise with clot removal, ICP monitoring, and decompressive craniotomy is likewise given a rousing “uncertain benefit” rating, and garners the ubiquitous “requires more study” moniker (except surgery for deteriorating cerebellar hemorrhage).
If blood pressure control is attempted in the ED, still theoretical and controversial, all agree that short-acting IV agents should be used. I prefer labetalol, with intermittent boluses, and then a drip to control subsequent pressure. I also like nicardipine, neurosurgeon's favorite because of its potential antispasmodic effect on cerebral blood vessels. Nitroprussid e and hydralizine are problematic, and their use is not totally embraced. Esmolol is simply too complicated while the ED staff is attending to airway, aspiration potential, and the mammoth task of expediting studies, calling consultants, and whisking these critically ill patients to the neuro ICU.
Let's look more closely at hematoma expansion after ICH. To make things more confusing, Jauch et al concluded that about 40 percent of patients with ICH experienced substantial hematoma growth within 20 hours. (Stroke 2006;37:2061.) An amazing 28 percent had clot expansion within one hour, long any before blood pressure control could logically take place. Neither baseline, peak hemodynamic parameters, nor change in heart rate and blood pressure parameters were significantly associated with hematoma growth. It looks like clots expand, or don't, on a whim, with minds of their own under the influence of things other than blood pressure. So much for limiting clot growth by simply lowering the pressure.
Summary: While theories may ultimately be proven, the AHA and ASA based their recommendations on minimal data. No generally accepted standard of care exists for treating hypertension in the immediate post-ICH period. It is not even certain that blood pressure control limits clot expansion. While it is “probably” safe to lower the systolic blood pressure to 140 mm Hg systolic in those who are markedly hypertensive, with the hope (but unproven ability) of decreasing hematoma size and promoting a better outcome, this may be wishful thinking. We all want to do something, but rapidly lowering the pressure may not be the Holy Grail for patients who bleed into their brain. One wonders if anything you do with blood pressure is essentially mental meandering, of no harm or value at all. Maybe the body does know best.
Unfortunately, most of us have to make decisions on our own, and institute therapies based on common sense, a modicum of scientific data, and a do-no-harm approach. If someone normally has a blood pressure of 240/120 mm Hg and suffers an ICH, I am leery of rapidly lowering his blood pressure to 140 mm Hg systolic. And I'm not that good at a bedside gestalt of determining whether the ICP is elevated. I would be tempted to intervene in the systolic 180-220 mm Hg range, but it may be more prudent to wait, rethink, and let the ICU tackle the blood pressure problem. Remember, blood pressure changes with every heartbeat, so rethink constantly. It would be nice if our scientific societies would consider the hapless EP who must practice in a fishbowl. We are not clinicians whose only role in life is manipulating the blood pressure of new stroke patients in the war-zone morass of the ED, while attempting to provide reasonable care, not only to ICH patients but to dozens of others.
One could make the argument for doing absolutely nothing about blood pressure in the ED. There are no Class 1 recommendations in the 2010 guidelines mandating ED management of spontaneous ICH. These guidelines address emergency diagnosis and assessment, reversal of anticoagulation, and monitoring of glucose and seizure control, along with appropriate consultation and expeditious transfer to intensive care. I particularly like this recommendation: “Initial monitoring and management of ICH patients should take place in an intensive care unit, preferably one with physician and nursing neuroscience intensive care expertise.”
In their perfect world, it seems that the AHA and ASA have relieved the EP entirely from even initial monitoring and managing ICH patients in the ED. Simply get the patient to the ICU so the neuroradiologist, neurologist, and neurosurgeon can gleefully swarm to the patient. I invite the entire panel of experts to spend a day in my ED.
Can Intracranial Pressure Guide Blood Pressure Control in the First Few Hours of ICH?
It is reasonable to conclude, as a recent ACEP consensus report did, the “data are mixed about whether there is a relationship between increased BP at presentation and subsequent hematoma growth.” (Ann Emerg Med 2008;51(3 Suppl):S24.) To complicate matters, some suggest altering approaches to blood pressure control after ICH based on ICP. Simply drill a hole in the head, and insert ventricular catheters to measure this parameter. Slick for the neuro ICU, but it flummoxes me how the EP should determine ICP in the ED during an acute brain bleed, coincident with intubation, suctioning, x-raying, and prodding. It's an attractive thought but clearly promulgated by non-ED clinicians. It only takes one case after normal business hours to realize that ICP monitoring is essentially impossible when it might be needed most, although the actual need for ICP monitoring at all leaves one nonplussed at best. While ICP monitoring is intuitively nice, it's a totally unrealistic immediate tactic for most EDs.
Not to be discouraged by lack of science and based on hope and hype rather than rigorous data, the following has been promulgated: It seems that if the ICP is elevated, the blood pressure is allowed to be higher. Again, the mere mortal is nonplussed by the experts, and data are so murky, pontifications so loud, and proselytizing so bizarre, that one is left with an eerie sense of “say what?”
* Suspected increased ICP: An impaired pupil (not otherwise specified), CT parameters, or a GSC less than 8 suggests increased ICP. Suggestion: Keep the MAP “just below” 130 mm Hg (systolic less than 180 mm Hg) for 24 hours.
* No suspicion of increased ICP: Maintain MAP below 110 mm Hg (systolic BP less than 160 mm Hg) for 24 hours.
* Preferred antihypertensive agents: Labetalol, nicardipine, esmolol. Probably avoid nitroprusside and hydralizine because they may increase ICP (unproven effect on outcome).
*Note this quote from the 2010 AHA/ASA 2010 Guidelines: “The absence of published studies showing that management of elevated ICP impacts on ICH outcome makes the decision whether to monitor and treat elevated ICP unclear.
The Emergency Medicine Literature on Hypertension after Acute ICH
It is all well and good for academic neurologists and cardiovascular colleagues from national organizations to offer guidelines for emergency physicians. Many guidelines are based on ideal circumstances, unlimited resources, rapid response of consultants, and the availability of sophisticated monitoring techniques. At 2 a.m., however, the EP is usually on his own, at least for the first important decisions.
A recent emergency medicine perspective of blood pressure control issues after ICH was offered by Worster et al in the case of a 64-year-old man with an ICH whose initial blood pressure ranged around 195/115 mm Hg. (J Emerg Med 2009;37:433.) They asked if early intensive lowering of blood pressure reduce hematoma volume and improve clinical outcome after acute ICH. These authors from four academic emergency medical centers in the United States and Canada said ICH results in death and permanent disability among most patients.
While they acknowledge that aggressive blood pressure surveillance and intervention may prevent ICH, modern medicine has made little progress in treating it. There is even no consensus on surgical evacuation of a confirmed (noncerebellar) hematoma, intuitively a beneficial intervention. Even when one immediately stops CNS hemorrhage in an anticoagulated patient with activated factor V11a, with a reduction in the size of the hematoma, there is no proven benefit in mortality or morbidity, and with arterial thrombosis in other areas. Even though one may be able to reduce the size of the clot, no neurological benefit has ever been definitively demonstrated from this maneuver. While these observations pertain to anticoagulated patients, it would seem reasonable that similar physiology would occur in non-anticoagulated patients who spontaneously bleed.
To buttress their opinions, the authors review evidence from well known trials, including the INTERACT and ATACH studies that enamored the AHA and ASA. The conclusion reached by these academic EPs is the same that has frustrated clinicians for ages: “Aggressive blood pressure management may reduce hematoma volume in acute ICH, but there is no evidence of any beneficial impact on death or neurological outcomes.” They conclude there is insufficient evidence to support routinely lowering blood pressure in patients suffering from acute ICH.
Many recommendations may be driven by hubris by doctors think they can improve on what the body normally does with a bleeding brain. Everyone agrees that is seems like a good idea to lower severe hypertension in ICH, and it may be safe, even to the ranges of the new AHA and ASA guidelines in some undetermined subset. It is a tremendous leap from this unproven theory to defining standard of care, and holding physicians responsible for adhering to guidelines promulgated by well meaning experts from other specialties. While these authors suggest that the short answer is to follow the guidelines, there is no universally accepted standard of care for any physician. Fortunately, I have yet to see a formal standard of care pronouncement from the AHA and ASA. There is still a lot of “considering” going on out there.
As of April 2008, the Cochrane Collaboration concluded: “There is insufficient evidence to evaluate the effect of altering blood pressure on outcome during the acute phase of stroke (in the 12 trials reviewed). Functional outcome and death were not addressed by any of the [study] drugs.”
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2010 ICH Guidelines from the AHA and ASA
* Unchanged from previous guideline: Until ongoing clinical trials of blood pressure intervention for ICH are completed, physicians must manage blood pressure on the basis of the present incomplete efficacy evidence. Current suggested recommendations for target blood pressure in various situations are listed below. (Class IIb; Evidence Level: C.)
* New recommendation: In patients presenting with a systolic pressure of 150 to 220 mm Hg, acute lowering of systolic BP to 140 mm Hg is probably safe. (Class IIa; Evidence Level: B.) These recommendations do not address systolic blood pressure greater than 220 mm Hg.
Suggested Guidelines for Treating Elevated Blood Pressure in Spontaneous ICH*
Unchanged from 2007; Recommendations are Class C: Consensus opinion of experts.
* If systolic blood pressure is greater than 200 mm Hg or MAP is greater than 150 mm Hg, consider aggressively reducing blood pressure with continuous IV infusion and monitoring every five minutes.
* If systolic blood pressure is greater than 180 mm Hg or MAP is greater than 130 mm Hg with a possibility of elevated ICP, consider monitoring ICP and reducing pressure using intermittent or continuous IV medications while maintaining a cerebral perfusion pressure 60 mm Hg.
* If systolic blood pressure is greater than 180 mm Hg or MAP is greater than 130 mm Hg and there is no evidence of elevated ICP, consider a modest reduction of blood pressure (MAP of 110 mm Hg or target blood pressure of 160/90 mm Hg) using intermittent or continuous IV medications to control blood pressure and clinically reexamine the patient every 15 minutes.
* Interpretation by James Roberts, MD: This suggests that if the systolic blood pressure is 180 mm Hg or less or the MAP is 130 mm Hg or less, that NO BLOOD PRESSURE LOWERING IS AN ACCEPTABLE INITIAL APPROACH. Multiple measurements of the blood pressure or MAP are suggested before making clinical decisions.
Sources: Stroke 2010;41(9):2108; Stroke 2007;387(6):2001.
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