1 / 70

Blood pressure management in acute stroke

Blood pressure management in acute stroke . Oct 2011 J Lau Natalie Leung. Discussion topics. BP control in ICH BP control in ischaemic stroke BP control in SAH . Cerebral auto-regulation.

lorant
Download Presentation

Blood pressure management in acute stroke

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Blood pressure management in acute stroke Oct 2011 J Lau Natalie Leung

  2. Discussion topics • BP control in ICH • BP control in ischaemic stroke • BP control in SAH

  3. Cerebral auto-regulation • The mechanism by which cerebral blood flow remains constant across a wide range of cerebral perfusion pressures (CPP) • Maintains a constant CBF ~50ml/100g/min • This is achieved by reflex vasoconstriction or vasodilation of the cerebral arterioles in response to changes in perfusion pressure • CPP = MAP – ICP

  4. Cerebral auto-regulation • Cerebral blood flow is determined by CPP and cerebro-vascular resistance (CVR) • CVR is governed primarily by arteriolar diameter • Can maintain essentially constant CBF between a MAP of 50-60 mmHg to 150-160 mmHg • MAP < 50-60 mmHg [max. vasodilatation] -> CBF decreases proportionally with MAP -> ischaemia • MAP > 150-160 mmHg [max vasoconstriction] => CBF increases proportionally with MAP -> cerebral oedema & breakdown of BBB (ICH/encephalopathy)

  5. Cerebral auto-regulation • In chronically hypertensive patients, the auto-regulation curve is shifted as a result of elevated MAP levels. • The lower and upper limits are higher than in normal individuals • A normal CBF and oxygen consumption are maintained at the expense of a marked increase in the cerebro-vascular resistance • Resulting in decreased tolerance for relative hypotension, as the capacity to maintain a constant CBF at the lower end of the BP spectrum is impaired

  6. Cerebral auto-regulation

  7. Cerebral auto-regulation • Ischaemic penumbra • Tissue with the lowest CBF would be irreversibly damaged and constitutes the core of the infarct • The regions surrounding the core, the ‘penumbra’, are ischaemic and dysfunctional, but potentially salvageable (with timely re-perfusion) • This hypothesis suggests that BP reduction in the setting of acute ischaemic stroke may worsen hypo-perfusion of the penumbra and hasten extension of the infarct

  8. Cerebral auto-regulation

  9. Cerebral auto-regulation • In the ischemic penumbra, tissue perfusion follows perfusion pressure • any fall in blood pressure may precipitate ischemia, while an increase in blood pressure may cause edema and hemorrhagic transformation.

  10. BP control in ICH

  11. BP control in ICH • Elevated BP is seen to 46-56% of patients presenting with ICH • Studies have shown that hematoma expansion occurs very early within the first 24 hours in 38% of patients

  12. BP control in ICH • Potential patho-physiology • Stress activation of neuro-endocrine system (SNS, RAA, or gluco-corticoid system) • Increased ICP

  13. BP control in ICH • Effect of hypertension • hydrostatic expansion of hematoma • Peri- hematoma oedema • Re-bleeding • The growth of the bleed, which commonly occurs in the initial 3-6hrs • Could result in compression of the nearby structures in the brain, rapid deterioration of consciousness and death • Contribute to adverse outcomes in ICH

  14. BP control in ICH • Reducing BP in the early stages of a haemorrhage stroke may limit the amount of brain damage

  15. ? BP target in ICH High / low

  16. Argument for lowering BP in acute ICH • Initial haematoma volume and haematoma expansion are powerful predictors of mortality after ICH • Some studies suggested an association between high BP and haematoma expansion Davis SM, Broderick J, Hennerici M et al; Recombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology. 2006;66:1175–1181. Ohwaki K, Yano E, Nagashima et al. Blood pressure management in acute intracerebral hemorrhage: relationship between elevated blood pressure and hematoma enlargement. Stroke. 2004;35:1364 –1367

  17. 2 recent studies question this relationship… • In a series of 65 prospectively studied patients with ICH presenting within 3 hours • 37% had significant hematoma enlargement within 24 hours • Neither baseline nor peak BP was significantly associated with hematoma growth Jauch EC, Lindsell CJ, Adeoye O et al. Lack of evidence for an association between hemodynamic variables and hematoma growth in spontaneous intracerebral hemorrhage. Stroke. 2006;37:2061–2065.

  18. 2 recent studies question this relationship… • In another pooled analysis of 218 patients with onset of symptoms < 3 hours • hematoma volume was measured at presentation and 20 to 24 hours later • Percentage hematoma growth, initial ICH volume, GCS , and presence of IVH were all associated with increased mortality • However, BP was not Davis SM, Broderick J, Hennerici M et alRecombinant Activated Factor VII Intracerebral Hemorrhage Trial Investigators. Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology. 2006;66:1175–1181.

  19. Argument against lowering BP in acute ICH • Possible existence of a peri-hematomal ischaemic zone • Recent studies indicated that low blood flow around the haematoma may be a consequence of reduced cerebral metabolism in this area rather than a primary reduction of blood flow Zazulia AR, Diringer MN, Videen TO et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab. 2001;21: 804–810.

  20. Argument against lowering BP in acute ICH • Chronic hypertensives (due to a shift of auto-regulatory curve) and patients with increased ICP (due to lowered CPP) may develop cerebral ischemia if BP is acutely lowered 2 large trials….

  21. INTERACT trial • A multicentre, open, blinded outcome, RCT undertaken in 404 mainly Chinese patients in Australia, China and South Korea Lancet Neurol 2008; 7:391-99Craig S Anderson

  22. INTERACT trial • Methods • Intensive group: • SBP < 140mmHg • Achieve the target BP within 1hr of randomization and maintain the target level for next 7 days • Standard guideline-based group (based on AHA guideline published in 1999) • SBP <180mmHg • Outcomes • Absolute and proportional increase in haematoma and perihaematoma edema vol during the first 72hrs after ICH

  23. Results • Intensive treatment vs standard control • A trend towards lower relative and absolute growth in hematoma volumes from baseline to 24 hours in the intensive tx group • No excess of neurological deterioration or other adverse events related to intensive BP lowering

  24. Results • Since haematoma growth is a strong predictor of morbidity and mortality in ICH • Possible benefits of rapid physiological control of elevated BP • INTERACT2, which aims to determine the effects of treatment on clinical outcomes in 2800 patients with ICH, started recruitment in 2008

  25. ATACH trial • ATACH trial (Antihypertensive Treatment in Acute Cerebral Haemorrhage trial) • Phase I study, dose-escalation, multicentre prospective study • To determine the feasibility and acute safety of 3 levels of SBP reduction in subjects with ICH within 6 hrs after symptoms onset By University of Minnesota-Clinical and Translational Science Institue and National Institute of Neurological Disorders and Stroke (NINDS)

  26. ATACH trial • Intervention • Intravenous nicardipine to reduce systolic blood pressure to a target of: • (1) 170 to 200 mm Hg in the first cohort of patients • (2) 140 to 170 mm Hg in the second cohort • (3) 110 to 140 mm Hg in the third cohort • Treatment will last 18 to 24 hours. Participants will stay in the hospital for about 7 days (including 24 hours in the intensive care unit for close monitoring)

  27. ATACH trial • Primary outcomes • (1) treatment feasibility (achieving and maintaining the systolic blood pressure goals for 18-24 hrs) • (2) neurologic deterioration within 24 hrs • (3) serious adverse events within 72 hrs

  28. ATACH trial • Results: • The observed proportions of neurologic deterioration and serious adverse events were below the prespecified safety thresholds • 3-month mortality rate was lower than expected in all systolic blood pressure tiers • The results form the basis of a larger randomized trial addressing the efficacy of systolic blood pressure reduction in patients with intracerebral hemorrhage

  29. ATACH II • Phase III randomised study • Determine the efficacy of early intensive treatment (<140mmHg) relative to the standard treatment (<180mmHg) with Nicardipine infusion (within 3 hrs of symptom onset) • Quality of life (EuroQol at 3 months) • Death and disability at 3 months • Proportion of haematoma expansion • Safety of intensive treatment relative to the standard treatment in the proportion of subjects with treatment-related serious adverse events within 72 hours.

  30. ATACH II • Estimated no. of patients: ~ 1280 • Estimated study completion date: July 2016

  31. What BP level is too high and requires immediate reduction? • SBP > 180mm Hg or • MAP >130 mmHg • Lower BP targets may be appropriate if concomitant • heart failure, HT encephalopathy, active cardiac ischemia etc

  32. What is the appropriate target BP in patients with ICH?

  33. AHA/ASA recommendations for BP Mx in ICH • If SBP >200 mmHg or MAP >150 mmHg • consider aggressive reduction of BP with continuous IV infusion • frequent BP monitoring every 5 minutes • If SBP > 180 mmHg or MAP >130 mmHg, and there is the possibility of raised ICP • consider monitoring ICP • reducing BP using intermittent or continuous IV medications while maintaining a cerebral perfusion pressure > or = 60 mmHg

  34. AHA/ASA recommendations for BP Mx in ICH • If SBP > 180 mmHg or MAP >130 mmHg, and there is no evidence of raised ICP • consider a modest reduction of BP (e.g. MAP of 110 mmHg or target BP of 160/90 mmHg) using intermittent or continuous IV medications to control BP • clinically re-examine the patient every 15 minutes

  35. How fast should BP be lowered? • Lowering MAP by no more than 20% in the first 24 hours • Rapidly lowering MAP by ~15% does not lower cerebral blood flow • Lowering MAP >20% may do so According to results of small studies

  36. What medications may be considered in the acute setting? • Short and rapidly acting IV anti-hypertensive medications • Labetolol • Hydralazine • Esmolol • Nicardipine • Enalapril • Nitroglycerin • Nitroprusside

  37. What medications may be considered in the acute setting? • Large studies comparing various anti-hypertensives are not a/v • Caution about the use of sodium nitroprusside and nitroglycerin • Can potentially increase ICP

  38. BP control in ischaemic stroke

  39. BP control in ischaemic stroke • An elevated BP, that often declines spontaneously, is seen on presentation in most patients (>60%) with acute ischaemic stroke • In most cases, BP declines in the first few days after stroke onset, but a significant decline can be seen even in the first few hours after onset in ~ 1/3 of patients • A study reported that there was a greater spontaneous decrease in BP after admission in patients who recanalized after intra-arterial thrombolysis c/w patients with inadequate recanalization Mattle HP, Kappeler L, Arnold M, et al. Blood pressure and vessel recanalization in the first hours after ischaemic stroke. Stroke 2005;36: 264-8

  40. BP control in ischaemic stroke • Potential patho-physiology • The elevation in BP may be secondary to the stress of the CVA, a full bladder, nausea, pain, pre-existing hypertension, a physiological response to hypoxia, or a response to raised ICP

  41. BP control in ischaemic stroke • Theoretically reasons for lowering BP • Reduce formation of brain oedema • lesser the risk of haemorrhagic transformation, prevent further vascular damage/early recurrent CVA

  42. BP control in ischaemic stroke • Paucity of clinical trial data • In the absence of other organ dysfunction necessitating rapid reduction of BP, or in the setting of thrombolytic therapy • little scientific evidence and no clinically established benefit for rapid lowering of BP • A cochrane review of 218 patients from 5 clinical trials concluded that the data were insufficient to make a firm recommendation on the value of acute BP reduction after stroke

  43. BP control in ischaemic stroke • International Stroke Trial • Evaluates more than 17000 patients • U-shaped relationship btw BP & mortality • Early death increased by 17.9% for every 10mmHg below a SBP of 150 mmHg, and by 3.8% for every 10 mm Hg above

  44. BP control in ischaemic stroke • INWEST trial • Intravenous Nimodipine West European trial • 3 treatment groups: • Placebo (n=100) • Nimodipine 1 mg/hr (n=101) • Nimodipine 2mg/hr (n = 94) • The target population was 600 subjects, but the trial was stopped after recruiting 295 subjects because of an imbalance in the outcomes showing worse outcomes in the groups treated with nimodipine Effect of Intravenous Nimodipine on Blood Pressure and Outcome After Acute StrokeStroke. 2000;31:1250 Niaz Ahmed

  45. BP control in ischaemic stroke • INWEST trial • SBP dropped from baseline • Placebo group: 2.1% • Low dose group:6.6% • High dose group: 11.4%

  46. BP control in ischaemic stroke • Results • High-dose group • DBP reduction of ≥20% • a significantly increased adjusted OR for the compound outcome variable death or dependency and death alone compared with all placebo patients

More Related