Opioids: Might depress cerebral perfusion pressure

 

Sedation for critically ill adults with severe traumatic brain injury: A systematic review of randomized controlled trials; Roberts DJ, Hall RI, Kramer AH, Robertson HL, Gallagher CN, Zygun DA; Critical Care Medicine 39 (12),

 

OBJECTIVES: To summarize randomized controlled trials on the effects of sedative agents on neurologic outcome, mortality, intracranial pressure, cerebral perfusion pressure, and adverse drug events in critically ill adults with severe traumatic brain injury. DATA SOURCES: PubMed, MEDLINE, EMBASE, the Cochrane Database, Google Scholar, two clinical trials registries, personal files, and reference lists of included articles. STUDY SELECTION: Randomized controlled trials of propofol, ketamine, etomidate, and agents from the opioid, benzodiazepine, α-2 agonist, and antipsychotic drug classes for management of adult intensive care unit patients with severe traumatic brain injury. DATA EXTRACTION: In duplicate and independently, two investigators extracted data and evaluated methodologic quality and results. DATA SYNTHESIS: Among 1,892 citations, 13 randomized controlled trials enrolling 380 patients met inclusion criteria. Long-term sedation (≥24 hrs) was addressed in six studies, whereas a bolus dose, short infusion, or doubling of plasma drug concentration was investigated in remaining trials. Most trials did not describe baseline traumatic brain injury prognostic factors or important cointerventions. Eight trials possibly or definitely concealed allocation and six were blinded. Insufficient data exist regarding the effects of sedative agents on neurologic outcome or mortality. Although their effects are likely transient, bolus doses of opioids may increase intracranial pressure and decrease cerebral perfusion pressure. In one study, a long-term infusion of propofol vs. morphine was associated with a reduced requirement for intracranial pressure-lowering cointerventions and a lower intracranial pressure on the third day. Trials of propofol vs. midazolam and ketamine vs. sufentanil found no difference between agents in intracranial pressure and cerebral perfusion pressure. CONCLUSIONS: This systematic review found no convincing evidence that one sedative agent is more efficacious than another for improvement of patient-centered outcomes, intracranial pressure, or cerebral perfusion pressure in critically ill adults with severe traumatic brain injury. High bolus doses of opioids, however, have potentially deleterious effects on intracranial pressure and cerebral perfusion pressure. Adequately powered, high-quality, randomized controlled trials are urgently warranted.

 

Blogger note:  take home message is in bold above.  Until the definitive study is done, pay attention if, to nothing else, that one sentence.

Bevacizumab, metastasis, and brain hemorrhage, True, true and unrelated?

Intracranial hemorrhage in patients treated with bevacizumab: Report of two cases; Nishimura T, Furihata M, Kubo H, Tani M, Agawa S, Setoyama R, Toyoda T; World Journal of Gastroenterology 17 (39), 4440-4 (Oct 2011)

Treatment with bevacizumab, an antiangiogenic agent, in patients with metastatic or unresectable colorectal cancer was approved less than 4 years ago in Japan. Bevacizumab improves the survival of patients with metastatic colorectal cancer; however, it may lead to complications such as bleeding, which are sometimes fatal. Bevacizumab should be administered only after careful consideration because the potential risks of therapy outweigh its benefits. Therefore, pharmaceutical companies do not recommend bevacizumab therapy for patients with brain metastases. While some reports support the cautious use of bevacizumab, others report that it is not always necessary to prohibit its use in patients with metastases to the central nervous system (CNS), including the brain. Thus, bevacizumab therapy in colorectal cancer patients with brain metastases is controversial, and it is unclear whether brain metastases are a risk factor for intracranial hemorrhage during anti-vascular endothelial growth factor (VEGF) therapy. We report a 64-year-old man and a 65-year-old man with recurrent colorectal cancer without brain metastases; these patients developed multifocal and solitary intracranial hemorrhage, respectively, after the administration of bevacizumab. Our findings suggest that intracranial hemorrhage can occur even if the patient does not have brain metastases prior to bevacizumab treatment and also suggest that brain metastases are not a risk factor for intracranial hemorrhage with bevacizumab treatment. These findings also question the necessity of excluding patients with brain metastases from clinical trials on anti-VEGF therapy.

Blogger note:  Paper intrigues but any number of conclusions could be drawn out of it.  Larger experience is required.

Stroke centers and survival

Does primary stroke center certification change ED diagnosis, utilization, and disposition of patients with acute stroke?; Ballard DW, Reed ME, Huang J, Kramer BJ, Hsu J, Chettipally U; American Journal of Emergency Medicine (Nov 2011)

BACKGROUND AND PURPOSE: We examined the impact of primary stroke center (PSC) certification on emergency department (ED) use and outcomes within an integrated delivery system in which EDs underwent staggered certification. METHODS: A retrospective cohort study of 30 461 patients seen in 17 integrated delivery system EDs with a primary diagnosis of transient ischemic attack (TIA), intracranial hemorrhage, or ischemic stroke between 2005 and 2008 was conducted. We compared ED stroke patient visits across hospitals for (1) temporal trends and (2) pre- and post-PSC certification-using logistic and linear regression models to adjust for comorbidities, patient characteristics, and calendar time, to examine major outcomes (ED throughput time, hospital admission, radiographic imaging utilization and throughput, and mortality) across certification stages. RESULTS: There were 15 687 precertification ED visits and 11 040 postcertification visits. Primary stroke center certification was associated with significant changes in care processes associated with PSC certification process, including (1) ED throughput for patients with intracranial hemorrhage (55 minutes faster), (2) increased utilization of cranial magnetic resonance imaging for patients with ischemic stroke (odds ratio, 1.88; 95% confidence interval, 1.36-2.60), and (3) decrease in time to radiographic imaging for most modalities, including cranial computed tomography done within 6 hours of ED arrival (TIA: 12 minutes faster, ischemic stroke: 11 minutes faster), magnetic resonance imaging for patients with ischemic stroke (197 minutes faster), and carotid Doppler sonography for TIA patients (138 minutes faster). There were no significant changes in survival. CONCLUSIONS: Stroke center certification was associated with significant changes in ED admission and radiographic utilization patterns, without measurable improvements in survival.

 

Blogger note:  Small select group of stroke patients, those given alteplase, may be less than 5 percent of the total and are the only ones who would be expected to do better in primary stroke centers.  However, the target group is likely to be buried in the statistics of 15,000 patients reviewed.  This type of stroke center evaluation might be better suited for evaluating specific populations receiving specific treatments.

Which antihypertensive? Beta blockers risky

Webb et al.  Lancet 2010 375:905-915

Idea  BP variability is worse than absolute measurement of a high BP.  Certain drugs such as Beta blockers are associated with high variability and therefore higher risk, whereas Calcium channel blockers have less variability in BP and are therefore better for stroke prevention.  ACE inhibitors trend bad, ARBs slightly better.

lifestyle choices and stroke prevention risk

Chiuve et al. Circulation 2008; 118:947-954

43,685 men Health professionals followup study

71,243 women Nurses health study

Five factors:

1.  Not smoking

2.  healthy diet

3.  30 minutes per day vigorous activity

4.  Weight BMI< 25

5.  one alcoholic drink per day for women, 1-2 for men

80 percent reduction in risk, dose dependent on how many followed.

Partly related to secondary effects of above on blood pressure.  Amount of BP reduction per lifestyle aspect adopted

10 kg weight reduction= 5-20 mm HG

DASH eating plan 8-14 mm

dietary sodium restriction  5-8

physical activity 4-9 mm

moderate alcohol consumtpion 2-4 mm

Chobanian JAMA 2003; 289:2560

Every 10 mm   reduction in BP leads to a 31 % stroke risk

Lawes et al. Stroke 2004; 35:776

Carrascal and Guerrero- Stroke and CABG part II

from the Neurologist

Perioperative risk factors:
1.  CPB use and factors that are uncontrollable including low flow
2.  Type of procedure-- 3 fold risk in patients undergoing open chamber procedure.Combined procedures eg. CABG + valve causes baseline increase from 5 to 16 % or so
3.  Duration-- number of emboli increase by 90.5 % for every hour
4.  Postoperative complications including low CO (due to MI eg.) or postoperative AFIB which is common in first 4 days.

III Preventive Procedures--
 Operatively
A.  Minimize aortic manipulation -- one cross clamp not multiple, or even zero with pediculate anastomoses
B.  Heart Port Clamp-- instead of external clamp, use a saline filled balloon and clamp internally avoiding manipulation
C.  Identify aortic disease with epiaortic ultrasound; if needed use femoral or axillary catheterization and / or profound hypothermia.
D.  Use side hole not end hole cannulas-- less displacement of particle
E.  Use intraaortic filtration-- not shown to be beneficial YET
F.Dispersion aortic cannulas when friable valves are diagnosed
G.  Carotid surgery according to above criteria
H.  Prophylactic resection of atrial appendage in patients with preexisting AF who also need MVR

Reduce microemboli in CPB Circuit
A. heparin bound CPB circuit
B. Membrane rather than bubble oxygenator
C. CO2 sufflation into thoracic wound to decrease air bubbles
D.  Filter in arterial line; leukocyte filter to decrease inflammatory response
E.  Decrease CPB time
F.  Decrease cardiotomy suction to prevent lipid microemboli and improve cognitive; us ultrasound to help
G.  Early slow rewarming 0.2 degrees C per minute
H.  Alphastat protocol for pH and CO2
I.    Reduce perfusionists' interventions which are directly tied to cognitive decline
J.  Avoid collecting/reinfusing mediastinal blood
K.  Emblocker ultrasound transducer on aorta redirects debris to descending aorta, tried in animals so far

Prevention of ischemic injury
A.  Keep MAP> 50
B.  Avoid maneuvers that increase CVP (CPP = MAP-CVP)
C.  Avoid cardiac luxation during off pump procedures which can lower CO
D.  Pulsatile flow not shown to be superior to continuous flow
E.  Substitute Aprinin for amicar or transxemic acid
F.  Avoid profound hemodilution especially in octagenerarians

Metabolic
A.  Avoid hyperglycemia
B.  Keep HCT over 30

Neuroprotection
Summary
Many have been studied none have shown effective

Bypass and stroke Pt !

also see blog post regarding Lou Caplan's opinion regarding the issue http://strokenotes.blogspot.com/search?q=cabg

Carrascal Y, Guerrerro AL.  Neurological damage related to cardiac surgery; pathophysiology, diagnostic tools, and prevention strategies. Using actual knowledge for planning the future.  The Neurologist 2010; 16:152-164.

Summary-- the population undergoing cardiac surgery is older and sicker.  Prevention efforts should include improvements in surgical techniques and cerebral protection, pharmacotherapy, and adequate neuropsychologic assessments. 

Bullet points: Intro
1. 1-6 % of patients have neurologic complications, but number is up to 15 % in high risk group and up to 50 % if you count cognitive dysfunction.  Neurologic complications increase one year mortality tenfold in first year, and doubles ICU care time.  31 % of patients with neurologic damage return home, 75 % with "minor" cognitive damage, 85 % without neurologic damage. 

I.  Mechanism of damage in cardiopulmonary bypass:  emboli (micro or macro), inflammatory response, metabolic response to hypoxemia or vasogenic or cytotoxic edema, and cerebral hypoperfusion

A.  Emboli
1) Macro, > 200 um, related to manipulation of aorta, calcium, valvular debris.  Causes focal deficits. 
2) Micro, <200 um, due to a) air, related to opening chambers of heart, generation in CPB machine, and during patient rewarming   b)  lipids, especially due to cardiotomy suction especially with lipid reinfusion into CPB circuit   c)  cellular aggregate esp platelets     d)  Exogenous material from heart lung machine such as silicon.  Microemboli go to border zone, to basal ganglia and white matter tracts.  TCD detection of microemboli over 60 correlates with a 70 % risk of cognitive damage.  TCD does not detect type of particle.
Intraoperative TEE detects air bubbles in chambers and diseased arteries that can be avoided for cross clamping.  Aortic intimal thickening over 3 mm, especially with rounded, protruberant or ulcerated plaque is associated with a 4.5 x risk of neurologic sequelae.  Post op stroke is 25 % with a mobile plaque, 8 % with a fixed plaque, and 1.8 % if there is no plaque. 

B.  Inflammatory response activation-- duet to CPB, leads to a coagulation cascade and damage to blood brain barrier. 

C.  Disorders in Neuronal Metabolism secondary to hypoxemia or vasogenic or cytotoxic edema-- related to hypothermia during procedure, which has good and bad points, although mild hypothermia seems to benefit.  Severe may lead to brain edema.

D.  Hypoperfusion--

II Detection
A..Biochemical markers of neuropsychological damage-- adenylate kinase (good), CK-BB (bad marker, totally nonspecific), neuronal specific enolase (good marker, raised levels over 35 ng/ml after 48 hours correlates with bad prognosis, S100 B is a white matter marker, good marker more than 24 hours out (early rise occurs during CPB and is not prognostic) Level of > .5 ug/mL at 48 hours have a 78 % mortality compared to 18 % with a level under .5.  S100B < 1.1 24 hours after surgery has a 97 % specificity to exclude stroke. 
B. Imaging- DWi and NIRS (near infrared spectroscopy) show clinically silent events in a MAJORITY of patients or at least 50 %.  Fluroescein retinal angiography can detect clinically silent retinal events.  and disappear 7 days postop
C.  Neuropscyh-- Studies not clear.  Risk factors (incremental) include DM, CRF, ascending aortic atherosclerosis, CVD, PVD, or previous severe neurologic disease. 

III Major risk factors for complications
A. Age
B.  Carotid disease (controversial)-- this author suggests there is a 10 % reduction of stroke risk if the artery is symptomatic and stenosis is > 50 %.  For asymptomatic , procedure only if patient has life expectancy > 5 years, is 40-70, mortality of procedure < 3 %. 
C.  Prior stroke confers 13-15 % risk no matter when the prior stroke
D.  PVD increases risk of perioperative stroke by 4.5 %, and affects 33 % of octagenarians.
E. Severe LV dysfunction and poor EF
F. Indirect risk factors : DM, RF, HTN, COPD
G. Baseline intellectual function
H.  Genetic factors (apoE) unsettled
I Gender-- women do worse

see next post

Reconsidering MI as a contraindication for IV thrombolysis for stroke

De Silva DA et al.  Neurology 2011; 76:1838-1840. 

General points

1.  Some guidelines suggest 90 days not to use t-pa, but risk exists only in those with transmural MI (for cardiac rupture) and in those cases the wall is healed within 7 weeks, or at least healing, with fibrosis and scarring maximized by then,  to  mitigate risk in younger stroke patients without transmural rupture. 

2.  There are only 3 reports of 5 elderly women with tamponade after stroke thrombolysis. 

3.  In cardiac literature, wall rupture occurs in first 48 hours in those with transmural MI. 

Atraumatic convexal subarachnoid hemorrhage

Clinical presentations, imaging patterns and etiologies.  Kumar S. et al.  Neurology 2010; 74: 893-399

Authors include LR Caplan

Convexal SAH is about 8 percent of all SAH.  Authors found 29 patients at Beth Israel, about two thirds were women.  There was a dichotomy in presentation by age.  The under 60's had a strong tendency to present with a severe headache, whereas that was rare in the over 60's, who presented with TIA-like presentations, migraine creeping numbness mimic (even repetitively) or lethargy.  Angiography/MRA/CTA was almost always negative.  The under 60's were most likely to have reversible cerebral vasoconstriction syndrome (formerly Call syndrome), whereas the over 60's were more likely to have amyloid angiopathy. The latter group tends to have recurrent disease, but this study does not have good followup.  Headaches often were prolonged, associated with retching or vomiting, and described as "thunderclap" in younger patients.  Surface eeg's were always negative for seizures among those presenting with repetitive sensory phenomena.  They were more likely to have superficial siderosis on imaging.

The differential of the presentation includes, in addition to the two above causes, cortical vein occlusion, PRES, coagulopathy, cocaine, lupus vasculitis, cavernoma, brain aneurysm, ephedra, HELLP syndrome, post LP headache, and arterial dissection.

Activated prothrombin complex for dabigratan bleed? one opinion

We recently had a 67-year-old man with atrial fibrillation who was
admitted from the EP lab after developing pericardial hemorrhage during
the procedure.  He had been taking dabigatran and had received his last
dose seven hours prior to the procedure.  He was undergoing an ablation
when a transseptal perforation occurred and hypotension ensued.  He had
received  5000 units of heparin prior to the start of the procedure.
Pericardiocentesis was undertaken and 4500 cc of blood was withdrawn.  He
was given two units of FFP  & Protamine 100 mg  with persistent bleeding.
He was then given  FEIBA (activated prothrombin complex) 3159 units (26
units per kilogram over 15 minutes).   One minute after initiating FEIBA
infusion slowing of the bleeding was observed.  Bleeding stopped from
pericardiocentesis within minutes of administration of FEIBA.  His PTT the
prior to the procedure was 53.  ACT prior to administration of heparin was
233. The PTT decreased to 35 after protamine infusion but prior to the
FEIBA administration, and decreased further to 29 following FEIBA. ACT
decreased to 131 following FEIBA.

Our single experience would suggest that FEIBA was effective in reversing
the anticoagulant effect of dabigatran.  I wonder if any others have had
an opportunity to use this treatment and what their experience has been?
Has anyone used other ways of reversing dabigatran and with what success?

normal thrombin time and dabagitan

(reprinted not practice in our facility)

A normal thrombin time essentially rules out any anticoagulant effect due to Dabigatran. Thrombin time is a widely available and inexpensive test. For patients known or suspected to be on Dabigatran, our stroke team policy is to consider treatment with IV-t-PA only when thrombin time is normal.

CADASIL typical temporal lobe imaging involving temporal pole

SAMMPRIS trial stopped

CLINICAL ALERT

The National Institute of Neurological Disorders and Stroke (NINDS) has stopped enrollment in a clinical trial that is evaluating whether intracranial angioplasty combined with stenting adds benefit to aggressive medical therapy alone for preventing stroke in patients with symptomatic intracranial arterial stenosis. The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) study is the first prospective randomized multicenter trial to compare aggressive medical management alone versus aggressive medical management plus angioplasty combined with stenting in patients with symptomatic high grade (70-99%) stenosis of a major intracranial artery (intracranial carotid, middle cerebral artery, intracranial vertebral artery, and basilar artery).

Full NINDS Alert (PDF)

billing code for administering alteplase by MS

You can use the CPT code 37195 if you are personally at the bedside while
> the tPA is given by a physician. 

Lambl's excrescences and fibrous strands

The serpentine mitral valve and cerebral embolism

James Ker

Cardiovascular Ultrasound 2011, 9:7 

 

Vilem Dusan Lambl, a Bohemian physician (1824-1895) were the first to describe the occurrence of small, filiform processes he observed on the aortic valve in 1856[5] . Today, these Lambl's excrescences are also referred to as valvular strands and have been observed on all native and prosthetic valves[5] . These strands may occur as single strands, in rows or even in clusters[5] . They can vary in length from 1 mm to 10 mm and are usually less than 1 mm in thickness[5] .

Valvular strands are composed of a fibroelastic, avascular core, covered by a layer of endothelial cells[5,6] .

The exact pathogenesis of formation of these structures are still unclear, however current opinion is that the initiating factor is that of an endocardial lesion in areas of trauma and/or high shear stress[5,6] . These denuded areas are then covered by fibrin with subsequent covering by an endothelial layer[5,6] . The prevalence of valvular strands has been estimated as 5.5% in a general population referred for transesophageal echocardiography and 40% in patients with stroke of unknown cause[1,2] .

The differential diagnosis for valvular strands includes the following[5] : a myxoma, thrombi, valvular vegetations, nonbacterial thrombotic (marantic) endocarditis, cardiac metastases, a fibroelastoma and other primary cardiac neoplasms.

Of all of the above, the most difficult distinction is that between a valvular strand and a fibroelastoma[5,7] . Histologically, these two entities are very similar with both containing a central core of elastic connective tissue, covered by endothelium. However, valvular strands are covered by a single layer of endothelial cells, but fibroelastomas contain regions of multiple layers of endothelial cells[5,7] .

Echocardiographically, fibroelastomas are more bulky, with stalks or pedestals sometimes present and multiple, fingerlike projections on their surface[5] . As fibroelastomas are usually found on the mechanically less strained parts of valves and endocardium they tend to be larger than valvular strands[5] . Valvular strands (Lambl's excrescences) are always found on the affected valve's line of closure and this limits their growth[5] .

Several published case reports have shown that valvular strands are associated with emboli to the coronary, pulmonary, spinal, retinal and cerebral circulation[1] .

Specifically regarding stroke, numerous reports have demonstrated an association with valvular strands, particularly in young patients[3,4,8,9] . The mechanism for embolic events is either that of thrombi forming on the strands which then embolize or it is possible that the valvular strand itself can embolize[2] . Direct visualization of thrombus on a valvular strand have indeed been described before[10] .

In conclusion, a case of a valvular strand, attached to the coapting edge of the mitral valve is presented, giving a serpentine appearance to the mitral valve. This valvular strand was the cause for a cerebral embolism which presented with a transient right sided hemiparesis. This is the only current case in the literature, where the combination of aspirin and clopidogrel is used for the prevention of further episodes of cerebral embolism. In the only randomized treatment study to date, no difference in relation to efficacy of warfarin compared to aspirin was found in patients with valvular strands and previous embolic episodes[2] . For this reason a combination of antiplatelet therapy was initiated as a therapeutic trial.

It is proposed that a randomized controlled study involving the combination of aspirin and clopidogrel is warranted in patients with valvular strands presenting with a first episode of cerebral embolism.

1. Wolf RC, Spiess J, Vasic N, Huber R: Valvular strands and ischemic stroke.

   Eur Neurol 2007, 57:227-231.

   Homma S, Di Tullio MR, Sciacca RR, Sacco RL, Mohr JP: Effect of aspirin and warfarin therapy in stroke patients with valvular strands.

2. Stroke 2004, 35:1436-1442.

   Freedberg RS, Goodkin GM, Perez JL, Tunick PA, Kronzon I: Valve strands are strongly associated with systemic embolization: A transesophageal echocardiographic study.

3. J Am Coll Cardiol 1995, 26:1709-1712.

   Roberts JK, Omarali I, Di Tullio MR, Sciacca RR, Sacco RL, Homma S: Valvular strands and cerebral ischemia. Effect of demographics and strand characteristics.

4. Stroke 1997, 28:2185-2188.

   Jaffe W, Figueredo VM: An example of Lambl's excrescences by transesophageal echocardiogram: A commonly misinterpreted lesion.

5. Echocardiography 2007, 24:1086-1089.

   Roldan CA, Shively BK, Crawford MH: Valve excrescences: Prevalence, evolution and risk for cardioembolism.

6. J Am Coll Cardiol 1997, 30:1308-1314.

   Gowda RM, Khan IA, Nair CK: Cardiac papillary fibroelastoma: A comprehensive analysis of 725 cases.

7. Am Heart J 2003, 146:404-410.

   Lee RJ, Bartzokis T, Yeoh TK, Grogin HR, Choi D, Schnittger I: Enhanced detection of intracardiac sources of cerebral emboli by transesophageal echocardiography.

8. Stroke 1991, 22:734-739.

   Tice FD, Slivka AP, Walz ET, Orsinelli DA, Pearson AC: Mitral valve strands in patients with focal cerebral ischemia.

9. Stroke 1996, 27:1183-1186.

   Nighoghossian N, Derex L, Loire R, Perinetti M, Honnorat J, Riche G, Barthelet M, Ninet J, Chazot G, Chassignolle J, Trouillas P: Giant Lambl excrescences.

10. Arch Neurol 1997, 54:41-44.

CLEAR trial link" t-pa plus integrilin

 

http://www.ncbi.nlm.nih.gov/pubmed/18772447

 

Random notes on abstracts from ISC meeting radiology

 

1.  Hyperdense MCA sign can disappear, but rarely does if LONGER THAN ONE CM

 

2.  High rCBV predicts good outcome irrespective of treatment suggesting collateral presence

 

3.  Multiple (>4) left hemisphere DWI lesions is predictive of aortic arch stroke

 

4.  The"brush sign" on 3 Tesla MRI may predict hemorrhagic conversion after stroke

 

ASPECTS score

 

is asociated with prognosis

http://www.aspectsinstroke.com/

http://radiopaedia.org/articles/alberta-stroke-program-early-ct-score

neurodoc

LAPSS and other stroke related scales

Los Angeles prehospital stroke screen : LAPSS

 http://www.strokecenter.org/trials/scales/lapss.html

 

LAMS Los Angeles Motor Scale

http://stroke.ahajournals.org/cgi/content/full/39/8/2264#TBL1508127

 

other scales

http://www.strokecenter.org/trials/scales/

 

 

 

neurodoc

Notes on Grotta talk- "Extending reach of patient eligibility"

presented at Genentech submeeting by Dr Grotta.    A few of his ideas
1.  We need to relax many of the criteria for i-v tpa so that 10-20 percent of patients get drug.  What IS needed to give drug is:  NIHHSS, time of onset, plain CT head, (no CTA till after infusion started), history of bleeding, seziures, surgery, stroke, meds, glucose, platelets and HCT.   NO Foley, CXR (unless suspicion of dissection), ECHO or INR unless on warfarin or heparin
2.  At his center, he has experience treating patients with wake-up strokes with success middling between placebo and standard 0-3 hour patients.
3.  Grotta believes that just as trauma is tiered into level one and two, so should stroke, and patients with level one stroke should be sent to comprehensive, not primary stroke centers where they can get better care.  The scale utilized could be one that differentiates likelihood of major vessel occlusion, the Los Angeles...... scale.
4. His research includes tpa followed y arbogatran

Notes of MRI talks at ISC 2011 by Michael Lev and by Greg Albers

These two talks demonstrate patients for whom intervention is NOT likely to help.

* BASIS (reference here: http://www.ajnr.org/cgi/reprint/29/6/1111 )

Lev

1.  Contrary to hypothesis, mismatch IS NOT discriminatory regarding clinical outcome after recanalization.  Most all M1 occlusions with small admission DWI have mismatch, but not all respond to therapy.  The independent outcome predictors, are, NIHSS <= 10 and BASIS* negative have good outcomes, NIHSS > 10 and BASIS + have poor outcomes  and those with one or other are intermediate.

2.  What you need to know, basically, is the amount of core infarct less than 70 cc.  If so, recanalization can be of benefit. You can measure this best, through DWI although CT can be used (see notes below).

3. The other thing you need to know is that a corresponding perfusion deficit exists.  These 2 criteria by MRI are specific but not sensitive for core.

4.  Idea of time is brain uses clock that starts with imaging of a DWI lesion less than 70 cc, not onset of symptoms. 

5.  Yoo Aj et al. Stroke 2010.  DWI and MTT volumes predicts outcome > mismatch.  DWI > 72 ml and NIHSS > 20 are associated with a poor outcome.  MTT < 47 mL and NIHSS < 8 have good outcome.  Combining gives prognosis over 70 %, much better than NIHSS alone (43 %) or imaging alone (54 %).

6.  Protocol is to do noncontrast head CT, then a CTA, then a DWI and only do CT perfusion if patient is not able to get a MRI.  Also notes current focus on radiation.

7.  Uses above characteristics to assess wake up strokes.

8.  Good collaterals is highly specific for small DWI

9.  THRESHOLDED CBF IS LESS VARIABLE THAN CBV AND IS MORE SENSITIVE FOR SALVAGEABLE BRAIN (CBV MORE SPECIFIC).  CT CBF NOT CBV IS "NEXT BEST THING" IF DWI IS NOT AVAILABLE TO DETERMINE SIZE OF CORE.  However there are issues with CT including luxury perfusion, standardization, post-processing and others.

ALBERS TALK

Discusses DEFUSE trial and adds that he criticizes Lev's talk because there is ANOTHER group of patients who do badly with recanalization and that is those with very large perfusion deficit even with a tiny DWI deficit who have a "malignant pattern" of infarct who will do much worse if treated.  A discussion ensued and Wade Smith mentioned a case with a "so-called malignant pattern" who was observed deteriorating, was promptly treated, and got better, therefore felt clinical part was important.  Again mismatch was overrated and not key.

Albers also spoke of converging evidence that > 5.5 or 6 seconds for contrast to reach brain was a threshold of very sick brain.  He also mentioned a case where one branch was not recanalized, but the branch that was recanalized reperfused dead tissue. 

Wade Smith talk

Many points not mentioned. Of interest he thinks IMS 3 is going to really open up intervention therapies.

Grotta talk "Extending reach of tpa eligibility"

presented at Genentech submeeting by Dr Grotta.    A few of his ideas

1.  We need to relax many of the criteria for i-v tpa so that 10-20 percent of patients get drug.  What IS needed to give drug is:  NIHHSS, time of onset, plain CT head, (no CTA till after infusion started), history of bleeding, seziures, surgery, stroke, meds, glucose, platelets and HCT.   NO Foley, CXR (unless suspicion of dissection), ECHO or INR unless on warfarin or heparin

2.  At his center, he has experience treating patients with wake-up strokes with success middling between placebo and standard 0-3 hour patients.

3.  Grotta believes that just as trauma is tiered into level one and two, so should stroke, and patients with level one stroke should be sent to comprehensive, not primary stroke centers where they can get better care.  The scale utilized could be one that differentiates likelihood of major vessel occlusion, the Los Angeles...... scale.

4. His research includes tpa followed by arbogatran, and TCD and hypothermia.

 

neurodoc

another opinion, references on cilostazol

A brief pubmed search about the topic showed a few studies and reviews on the subject. It appears that Cilostazol is non-inferior to aspirin per one study, and is effective in lowering cerebrovascular events with low rates of bleeding. I did not come across any studies that mention adverse events from using this drug. However, since it is not considered standard of care, it probably should only be used on an experimental basis with documentation as such- if it is used at all. Hope this helps.

Lancet Neurol. 2010 Oct;9(10):959-68. Epub 2010 Sep 15.

Cochrane Database Syst Rev. 2011 Jan 19;1:CD008076

J Stroke Cerebrovasc Dis. 2009 Nov-Dec;18(6):482-90.

 

cilostazol and stroke in Asians

Cochrane Database Syst Rev. 2011 Jan 19;1:CD008076.

Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin.

Kamal AK, Naqvi I, Husain MR, Khealani BA.

Stroke Service, Section of Neurology, Department of Medicine, Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi, Pakistan, 74800.

Abstract

BACKGROUND: Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke.

OBJECTIVES: To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascular risk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin.

SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010) and EMBASE (1980 to May 2010). In an effort to identify further published, ongoing and unpublished studies we searched journals, conference proceedings and ongoing trial registers, scanned reference lists from relevant studies and contacted trialists and Otsuka Pharmaceutical Co Ltd.

SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) comparing cilostazol with aspirin where participants were treated for at least one month and followed systematically for development of vascular events.

DATA COLLECTION AND ANALYSIS: Data extracted from eligible studies included: (1) a composite outcome of vascular events (stroke, myocardial infarction or vascular death) during follow up (primary outcome); (2) separate outcomes of stroke (ischaemic or haemorrhagic, fatal or non-fatal), myocardial infarction (MI) (fatal or non-fatal), vascular death and death from all causes; and (3) main outcomes of safety including any intracranial, extracranial or gastrointestinal (GI) haemorrhage and other outcomes during treatment follow up (secondary outcomes). We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all included studies.

MAIN RESULTS: We included two RCTs with 3477 Asian participants. Compared with aspirin, cilostazol was associated with a significantly lower risk of composite outcome of vascular events (6.77% versus 9.39%, risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91), and lower risk of haemorrhagic stroke (0.53% versus 2.01%, RR 0.26, 95% CI 0.13 to 0.55). In terms of outcome of safety compared with aspirin, cilostazol was significantly associated with minor adverse effects (8.22% versus 4.95%, RR 1.66, 95% CI 1.51 to 1.83).

AUTHORS' CONCLUSIONS: Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds.

PMID: 21249700 [PubMed - in process]