Updated tpa Guidelines: Expanding the opportunity for good outcomes. Benjamin Morrow, MSN RN UPMC Stroke Institute

Transcription

1 Updated tpa Guidelines: Expanding the opportunity for good outcomes Benjamin Morrow, MSN RN UPMC Stroke Institute 1

2 Outline History Current State Review Exclusions: Minor stroke symptoms Severe strokes Rapidly improving strokes Aneurysm Tumor Mimics 3 to 4.5 hour criteria 2

3 Objective Give More tpa!! 3

4 Case 1 67M with PMH of HTN arrived with EMS at 1502 with NIHSS 4 (1 aphasia, 2 right arm, 1 mouth droop) LSW per spouse Direct to CT scan (negative for ICH), glucose 104, BP 147/ NIHSS at 2 after improvement in speech and arm strength Decision made to NOT give tpa 1650 Admitted to inpatient unit with an NIHSS of 2 4

5 Stroke Across the United States Affects approximately 800,000 patients annually 5 th leading cause of death in the United States Leading cause of long term disability in the United States IV tpa has class IA recommendation for stroke patients meeting eligibility criteria Only 5% of stroke patients receive IV tpa 5

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7 Risk Factors for sich 1. SIZE OF INFARCT NIHSS >22, Edema Damage to underlying basal lamina and integrity of the vasculature Reperfusion (especially delayed) Hemorrhagic transformation is a natural evolution of stroke, thrombolytics exacerbate it. 2. Treatment with antiplatelets/anticoagulants 3. Medical Comorbidities HTN, DM, Fever 4. Older Age 7

8 43% good outcome 6 % sich NNT 8 56% good outcome 2.5 % sich (7% with NINDS criteria) NNT 14

9 tpa Recommendations Past 15 Years 2003 AHA/ASA Guideline for Early Management of Patients with Acute ischemic Stroke 2005 AHA/ASA Update to Guideline for Early Management of Patients with Acute ischemic Stroke AHA/ASA Guideline for Early Management of Patients with Acute ischemic Stroke 2009 AHA/ASA Expansion of the Time Window for Treatment with IV tpa 2013 AHA/ASA Guideline for Early Management of Patients with Acute ischemic Stroke 2015 Updated FDA label and Package insert for Alteplase 2015 AHA/ASA Scientific Rationale for Inclusion/Exclusion Criteria of IV tpa in Acute Ischemic Stroke 9

10 2013 AHA/ASA Inclusion Criteria Diagnosis of ischemic stroke causing measurable deficit Onset less than 3 hours before beginning treatment Age >18 Onset within 3 to 4.5 hours before beginning treatment Relative exclusions: Age >80 NIHSS >25 Use of oral anticoagulant regardless INR History of stroke and diabetes 10

11 2013 AHA/ASA Exclusion Criteria Significant head trauma or prior stroke in the previous 3 months Arterial puncture at non-compressible site in previous 7 days History of previous ICH or symptoms suggesting SAH Intracranial neoplasm, arteriovenous malformation, or aneurysm Recent intracranial or intraspinal surgery Elevated blood pressure (SBP >185 mm Hg or DBP >110 mm Hg) Active internal bleeding Platelet count < /mm3 Heparin received within 48 hours with abnormally elevated aptt Current use of anticoagulant with INR >1.7 or PT >15 seconds Use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated aptt, INR, ECT, TT, factor Xa activity assays) Blood glucose concentration <50 mg/dl (2.7 mmol/l) CT demonstrates large infarction 11

12 2013 AHA/ASA Relative Exclusion Criteria Minor or rapidly improving stroke symptoms Pregnancy Seizure at onset with postictal residual neurological impairments Major surgery or serious trauma within previous 14 days Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days) Recent acute myocardial infarction (within previous 3 months) 12

13 Relative Exclusions 3 to 4.5 Hour Window Age >80 NIHSS >25 Use of oral anticoagulant regardless INR History of stroke and diabetes 13

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15 15 Understand why patients are not receiving IV tpa Maximize number of patients eligible to IV tpa

16 Why Are Patients Not Receiving tpa? Delays in presentation Only 22% arrive within 3 hours Strict eligibility criteria 6-8% of all AIS are eligible for tpa If ALL AIS patients arrived in <3 hours, only 29% would be eligible based on NINDS criteria Mild stroke(43), HTN (10), Seizure (7), Bleeding Diathesis (6), Glucose (3) 16

17 17 Stroke Severity Mild and Rapidly Improving Strokes 31% of strokes arriving within 2 hours of LSW are excluded for mild or rapidly improving strokes 28% not discharged home 2 % mortality 10 % SNF 28% unable to ambulate independently at time of discharge Overall 2-15 % of mild AIS are treated with IV tpa

18 Case 1 67M with PMH of HTN arrived with EMS at 1502 with NIHSS 4 (1 aphasia, 2 right arm, 1 mouth droop) LSW per spouse Direct to CT scan (negative for ICH), glucose 104, BP 147/ NIHSS at 2 after improvement in speech and arm strength Decision made to NOT give tpa 1650 Admitted to inpatient unit with NIHSS MRI confirmed L parietal infarct and distal MCA branch occlusion Discharged to rehab on hospital day 3 NIHSS 5 ( 1 mouth droop, 2 R arm, 1 R leg, 1 aphasia) mrs at 8 week clinic visit 2 18

19 Stroke Severity Milder strokes with NIHSS < 4 have sich rate 0-2% Demonstrated benefit of IV tpa in mild stroke Think: Is this neurologic deficit disabling? 19

20 Disabling Symptoms? 20

21 Severe Strokes Stroke Severity Mild stroke (NIHSS <20) is the number one predictor of good outcome with or without treatment The treatment effect is consistent 22% vs 12% in patients with NIHSS >20 and age < 65 High NIHSS is a predictor of sich This does NOT outweigh the benefit of IV tpa in these patients High NIHSS is predictor of sich with or without tpa 21

22 AHA/ASA RECOMMENDATIONS For severe stroke symptoms, IV tpa is indicated within 3 hours despite increased risk of hemorrhage IV tpa is reasonable for patients with moderate to severe symptoms who demonstrate early improvement. Delaying treatment to monitor for further improvement is NOT recommended For patients with mild but none the less disabling symptoms who arrive within 3 hours IV tpa should be given, there should be NO exclusions because there is proven clinical benefit 22

23 The AHA recommends this as a treatment for acute ischemic stroke, it has also been used as first line treatment for urosepsis, seizures, and conversion disorder. What is IV tpa? Courtesy of Neuro ICU jeopardy. C Ratay

24 Mimics 24

25 Mimics 25

26 Risk Factors for sich 1. SIZE OF INFARCT (only independent risk factors) Damage to underlying basal lamina and integrity of the vasculature Reperfusion (especially delayed) Hemorrhagic transformation is a natural evolution of stroke, thrombolytics exacerbate it. 2. Treatment with antiplatelets/anticoagulants 3. Medical Comorbidities HTN, DM, Fever 4. Older Age These risk factors are generally not present in stroke mimics! 26

27 Mimics Blood glucose levels account for < 1 % of mimics and rarely result in focal neurologic deficits Generally accompanies other symptoms diaphoresis Hypo/hyperglycemia has not been shown to pose an increased risk of complications after IV tpa (0-2%) 27

28 Mimics Seizures at onset of AIS traditionally considered at contraindication Seizures can occur at onset of an AIS Of 300 patients described in reports of having received IV tpa after seizure, only 2 had sich 28

29 Mimics Low rate of mimics (<1%) Relative safety of IV tpa in mimics (0-2% sich) Frequent strokes accompanying glucose abnormalities and seizures Known harm in not administering IV tpa to AIS 29

30 AHA/ASA RECOMMENDATIONS IV tpa is reasonable in patients with a seizure at the time of onset of AIS if evidence suggests that residual symptoms are secondary to AIS Treating clinicians should be aware that hypo/hyperglycemia may mimic AIS and check blood glucose levels Treatment with IV tpa in patients with AIS who present with blood glucose >400mg/dl with subsequent correction is reasonable The risk of sich in conversion/psychogenic/malingering stroke mimics is quite low; starting intravenous t-pa is probably recommended in preference over delaying treatment to pursue additional testing 30

31 Intracranial Lesions Un-ruptured intracranial aneurysm is listed as exclusion for IV tpa in 2013 AHA/ASA guidelines Intracranial neoplasm is listed as exclusion for IV tpa in 2013 AHA/ASA guidelines 31

32 Aneurysm Unruptured aneurysm occurs in 2-3% of general population Case reports have been published on IV tpa in the setting of incidental aneurysm Mostly anterior circulation, mostly aneurysms <5mm NO difference in sich as compared to those without aneurysm AHA/ASA Recommendation for patients with acute ischemic stroke who are known to harbor a small or moderate-sized (<10mm) unruptured and unsecured aneurysm, IV tpa is reasonable 32

33 Intracranial Neoplasm Several case reports of sich in the setting of GBM have shown increased risk of sich Publications on IV tpa in extra-axial lesions (meningioma, paranasal tumors, etc.), show NO increase in sich AHA/ASA Recommendation IV tpa treatment is recommended for patients with acute ischemic stroke who harbor a known extra-axial intracranial neoplasm 33

34 3 to 4.5 Hour Exclusions Age > 80 NIHSS>25 PMH diabetes and CVA Use of oral anticoagulant, regardless of INR 34

35 3 to 4.5 Hour Window sich Ambulatory Age > 80 8 % vs 6.7% 19.5 % vs 17.7% NIHSS > % vs 10% 7.8% vs 10% OAC INR< % vs 6.8% 26.6% vs 24.7% PMH CVA and DM 6.9% vs 4.5% 34.9% vs 30.8% 35

36 3 to 4.5 Hour Exclusions Age > 80 AHA/ASA: IV tpa in the 3 to 4.5 hour window is safe and as effective as in younger patients NIHSS>25 AHA/ASA: Limited data, unclear benefit PMH diabetes and CVA AHA:ASA: IV tpa is as effective and safe as in the 0 to 3 hour window Use of Oral anticoagulant, regardless of INR AHA/ASA: For patients with INR < 1.7 in the 3 to 4.5 hour window IV tpa is safe and beneficial 36

37 Emergency Nursing Priorities Establish LSW Prioritize Diagnostics CT imaging and lab testing Perform and monitor NIHSS/neurologic exam within 15 minutes of arrival Obtain IV access - 1 peripheral IV Obtain weight for tpa dosing, ideally actual weight Administer thrombolytic therapy when ordered Monitor the post IV t-pa patient every 15 minutes with Vital Signs and NIHSS Observe for bleeding complications and neurologic changes 37

38 General Considerations Mix early Forget the Foley Coagulation studies are not required One IV is fine Written consent is not required 38

39 Conclusions Spread the word! Time to presentation is the number one reason for exclusion 39

40 Conclusions Do not delay for any reason Exclusion criteria are not always exclusions Consider symptom impact over NIHSS value and aggressively treat mild but disabling strokes Assess each case individually and consider risk benefit of treating AND of not treating 40

41 References Damaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, & Grotta JC, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. 2016; Stroke; 47: Nasr DM, Brinjiki W, Cloft HJ, Rabinstein AA.. Utilization of intravenous thrombolysis is increasing in the United States. Int J Stroke. 2013; 8: Tissue Plasminogen activator for acute ischmic stroke: the National Institute of Neurologic Disorders and Stroke rt-pa Stroke Study Group. N Eng J Med. 1995; 333: Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Eng J Med. 2008; 359: Kleindorfer DO, Kissela B, Schneider A, Woo D, Khoury J, Miller, R, et al. Eligibility for recombinant tissue-type plasminogen activator in acute ischemic stroke: a population based study. Stroke. 2004; 35: e27-e29. Smith EE et al. Outcomes in mild and rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With the Guidelines Stroke. Stroke. 2011; 42: De Los Rios la Rosa F, Khoury J, Kissela BM, Flaherty ML, Alwell K, Moomaw CJ, et al. Eligibility for intravenous recombinant tissue-type plasminogen activator within a population: the effect of the European Cooperative Acute Stroke Tsudy (ECASS0 III Trial. Stroke. 2012; 43: Jauch EC, Saver JL, Adams HP, Bruno A, Connors JJ, Demaershalk BM, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals form the American Heart Association/American Stroke Association. Stroke. 2013; 44: Demchuk AM, Tuanne D, Hill MD, Kasner SE, Hanson S, Grond M, et al. Predictors of good outcome after intravenous t-pa for acute ischemic stroke. Neurology. 2001; 57: Levine SR, Khatri P, Broderick JP, Grotta JC, Kasner SE, Kim D, et al. Review, historical context, and clarification of the NINDS rt-pa stroke trials exclusion criteria: Part 1: rapidly improving symptoms. Stroke. 2013; 44: Scott P, Seilbergliet R. Misdiagnosis of stroke in tissue plasminogen activator treated stroke patients: Characteristics and outcomes. Annals of Emergency Medicine. 2003; 42: Winkler DT, Fluri F, Fuhr P, Wetzel SG, Lyrer PA, Ruegg S, et al. Thrombolysis in stroke mimics: Frequency, clinical characteristics, and outcomes. Stroke. 2009; 40: Urra X, Ariño H, Llull L, Amaro S, et al. (2013) The Outcome of Patients with Mild Stroke Improves after Treatment with Systemic Thrombolysis. PLoS ONE 8(3): e doi: /journal.pone