1. Confirm that Neurology has been contacted
2. No heparin, aspirin, warfarin
3. For BP>220/120 (2 consecutive readings 10 min apart) give Labetalol 20mg IV over 2 min; if BP does not remain <220/120, give 40mg IV; then 60 mg IV; then 80mg IV; hold for HR<50
4. Vital signs/neuro checks now and q15 min; baseline temperature
5. Weight in kg: ______
6. O2 per N/C or mask to keep O2 sats >92%
7. STAT BG, notify Neurologist if >400mg/dl
8. 2 IVs: 18g saline lock
20g - start infusion of 0.9NS @75cc/hour
9. STAT BMP, CBC, platelets, PT/INR, PTT
10. STAT head CT without contrast
11. STAT EKG
12. Foley catheter if unable to void or if undergoes thrombolysis
Inclusion
- NIHSS > 10
- CT Angiogram shows large-vessel obstruction or occlusion (M1 or M2 MCA;Terminal ICA; Basilar artery)
- Symptom onset or last seen normal clearly established to be 3-6 hours inclusive (Note: if patient has had TIAs ensure that patient clearly returned to normal after each event. Otherwise patient is likely to have had a stroke and the exact timing of onset of lasting symptoms is a crucial determinant for eligibility. Additionally, patients waking with symptoms should be considered to have last been normal at time of retiring)
- Symptom onset < 3 hours but excluded from IV t-PA due to recent (< 24hrs) heparinization with elevated PTT ( > 1.5 times normal) (ie. cerebral or coronary angiogram/angioplasty) or recent non-intracranial surgery (< 2 weeks)
Exclusion
- CT shows early infarction/hypodensity of >1/3 of affected blood vessel distribution or any intracranial hemorrhage
- Recent Stroke < 3 months
- Recent MI < 3 weeks
- BP > 185/110 at time of treatment (Note: patient may receive prn meds to reduce BP to within this range prior to treatment, but if aggressive treatment is required or it is felt by treating physician that BP is not stable with these measures patient should be excluded)
- Rapidly improving symptoms
- Clinical history suggestive of subarachnoid hemorrhage even with normal CT.
- Platelets < 100 K ( Note: this is not an absolute value. Rather, patients with low platelet counts should be considered to have an underlying coagulopathy and therefore are at risk for hemorrhage due to coagulopathy and not because of absolute platelet count)
- History of one of the following
- Intracranial hemorrhage/Neoplasm/AVM
- Glucose < 50 or > 400 (Note: this may be corrected to see if symptoms resolve. If they do not resolve with normalization of values then patient may be considered eligible)
- Presumed septic embolus
Patients meeting above inclusion and exclusion criteria will first undergo urgent diagnostic angiography of presumed artery to be affecting stroke syndrome (target artery). Guide catheter and microcatheter selection will be determined at time of angiography by interventional radiologist. If target artery suspected is the internal carotid artery, injection of the common carotid artery to examine the carotid bifurcation and intracranial circulation will be performed first. If carotid occlusion is identified, with failure to opacify the carotid terminus, the opposite carotid artery and/ or vertebral artery will be injected to identify collateral flow. If no occlusion is identified then the posterior circulation will be examined by selective injection of one or both vertebral arteries.
If thrombus is identified in appropriate intracranial artery (ie. T-ICA or MCA) no further injections will be performed and intraarterial thrombolytic therapy will be immediately initiaited per protocol.
If no thrombus is identified in the vascular territory appropriate for the patints clinical syndrome then no thrombolytic therapy will be administered and the procedure will be terminated.
Please note that intraarterial therapy (drug delivery) must be started within 5 hours of symptom onset. Patients who have not arrived to angiography < 5 hours will not receive intraarterial thrombolytic therapy.
A. Heparinization
A baseline activated coagulation time (ACT) will be obtained at 1 and 2 hours. A 30 U/kg intravenous heparin bolus will be administered once the thrombus is identified and the decision to proceed with intraarterial thrombolytic drug delivery is decided. A heparin infusion will be maintained to keep ACT > 200 seconds. Heparin infusion will be discontinued upon completion of the procedure. A heparin flush solution will be administered via access sheath and guide catheter, and will be continued until removed.
B. Thrombolytic Drug Delivery
The microcatheter will be passed over guide-wire to the level of the occlusion. Reteplase will be infused proximal to thrombus at a rate of 1 unit/5minutes. Angiogram imaging will be performed after each unit of reteplase is given to assess status of recanalization. As the vessel/s recanalize, the catheter will be advanced to more distal thrombus sites and infusion continued at those sites. A maximum reteplase dose of 8 units will be given. Reteplase infusion will be terminated upon achieving TIMI grade 3 recanalization or when maximum reteplase dose is achieved.
Airway
Sedation will be avoided if possible. Conscious sedation will be considered if patient movement continuously interferes with safe administration of therapy. The anesthesiologist on call will be consulted at discretion of treating physicians. Patient should remain easily arousable.
Breathing
A respiratory therapist will be required to be present at the discretion of the treating physicians. Oxygen will be administered via nasal canula or mask and continuous pulse oximetry will be used throughout procedure to keep O 2 saturation > 92% and recorded with every 15 minute BPs. Respiratory rate will also be monitored and recorded every 15 minutes.
Blood pressure
BP will be monitored with NIABP cuff every 15 minutes throughout IA therapy and recorded. Labetalol 10-30 mg IVP will be used to keep SBP <185 and DBP <110 (see Appendix C). ACE Inhibitors will be avoided. If patient is requiring frequent boluses, they will be placed on IV Nicardipine (2.5-15 mg/hr) or Nitroprusside (0.5-10 mcg/kg/min) continuous infusion for better control. Normal saline boluses will be used to keep SBP >100.
Neurologic Status
Neurologic exam monitoring will be performed throughout procedure and recorded. Key exam elements will include LOC questioning in addition to pre-procedure deficits. Complete NIHSS will be scored after IA is completed and again at 24 hrs. If sedation is used this should be documented in exam recording. If decompensation occurs at any time during therapy delivery it will assumed to be due to intracranial hemorrhage and intraarterial therapy and heparin will be stopped and procedure will be interrupted. Intracranial Hemorrhage protocol will be activated. Patient will be taken immediately to CT scanner for urgent CT head to assess for hemorrhage. Note: If CT does not demonstrate hemorrhage or significant mass effect with edema then therapy and procedure will be resumed.
Appendices
A. NIHSS
B. TIMI angiographic flow grading system
C. Blood pressure management protocol
D. Intracerebral or retroperitoneal hemorrhage protocol
References
Del Zoppo Gregory J. Thrombolytic therapy in cerebrovascular disease. Stroke 1988;19:1174-1179.
Haley E.Clarke. Thombolytic therapy for acute ischemic stroke. Clin Neuropharm 1993; 16:179-194.
Barnwell SL, Clark WM, Nguyen TT. Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke. Am J Neuroradiol November 1994;15:1817-1822.
Barr JD, Mathis JM, Wildenhain SL. Acute stroke intervention with intraarterial urokinase infusion. J Vasc Interven Radiol 1994;5:705-713.
NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581-7.
Lanzieri CF, Tarr RW, Landis D. Cost-effectiveness of emergency intraarterial intracerebral thrombolysis: a pilot study. Am J Neuroradiol November 1995;16:1987-1993.
Barnwell SL, Nesbit GM, Clark WM. Local thrombolytic therapy for Cerebrovascular disease: current Oregon health sciences university experience. J Vasc Interven Radiol 1995;6:78S-82S.
Baron JC, von Kummer R, Del Zoppo GJ. Treatment of acute ischemic stroke: challenging the concept of a rigid and universal time window. Stroke 1995;26:2219-2221.
Endo S, Kuwayama N, Hirashima Y. Results of urgent thrombolysis in patients with major stroke and atherothrombotic ocllusion of the cervical internal carotid artery. Am J Neuroradiol June 1998;19:1169-1175.
Del Zoppo G. Higashida R, Furlan A. PROACT: A phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke 1998;29:4-11.
Trouillas P, Nighoghossian n, Derex L. Thrombolysis with intravenous rt-PA in a series of 100 cases of acute carotid territory stroke: determination of etiological, topographic and radiological outcome factors. Stroke 1998;29:2529-2540.
Hacke W, Kaste M, Fieschi C. Randomized double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998;298;352:12545-51
Gonner F, Remonda L, Mattle H. Local intra-arterial thrombolysis in acute ischemic stroke. Stroke 1998;29:1894-1900.
Grond M, Stenzel Christoph, Schmulling S. Early intravenous thrombolysis for acute ischemic stroke in a community-based approach. Stroke 1998;29:1544-1549.
Jahan R, Duckwiler GR, Kidwell CS. Intraarterail thrombolysis for treatment of acute stroke: experience in 26 patients with long-term follow-up. Am J Neuroradiol August 1999;20:1291-1299.
Edwards MT, Murphy MM, Geraghty JJ. Intra-arterial cerebral thrombolysis for acute ischemic stroke in a community hospital. Am J Neuroradiol October 1999;20:1682-1687.
Furlan A, Higashida R, Wechsler L. Intra-arterial pro-urokinase for acute ischemic stroke; the PROACT II study: a randomized controlled trial. JAMA 1999;282:2003-2011
Clark WM, Wissman S, Albers GW. Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. JAMA 1999;282:2019-2026.
NINDS rt-PA Study Group. Effects of tissue plasminogen activator for acute ischemic stroke at one year. N Engl J Med 1999;340:1781-7.
Hoffman AI, Lambiase RE, Haas RA. Acute vertebrobasilar occlusion:treatment with high-dose intraarterial urokinase. Am J Radiol March 1999;172:709-712.
Lewandowski CA, Frankel M, Tomsick TA. EMS Bridging Trial Investigators. Combined intravenous and intra-arterial r-tpa versus intra-arterial therapy of acute ischemic stroke. Stroke 1999;30:2598-2605.
Abou-Chebl A, Furlan AJ. Intra-arterial thrombolysis in acute stroke. Curr Opin Neurol 2000;13:51-55.
Verstraete M. Third-generation thrombolytic drugs. Am J Med 2000;109:52-58.
Clark WM, Albers GW, Madden KP. The rtPA (Alteplase ) 0- to 6-Hour Acute Stroke Trial Part A (A0276g): results of a double-blind, placebo-controlled, multicenter study. Stroke 2000;31:811-816.
Albers GW, Bates VE, Clark WM. Intravenous tissue-type plasminogen activator for treatment of acute stroke: the standard treatment with alteplase to reverse stroke (STARS) study. JAMA 2000;283:1145-1150.
Ernst R, Pancioli A, Tomsick T. Combined intravenous and intra-arterial recombinant tissue plasminogen activator in acute ischemic stroke. Stroke 2000;31:2552-2557.
Katzan IL, Furlan AJ, Lloyd LE. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland experience. JAMA 2000;283:1151-1158.
Buchan AM, Barber PA, Newcommon N. Effectiveness of t-PA in acute ischemic stroke: Outcome relates to appropriateness. Neurology 2000;54:679-684.
Keris Valdis, Rudnicka S, Vorona V. Combined intraarterial/intravenous thrombolysis for acut ischemic stroke. Am J Neuroradiol February 2001;22:352-358.
Qureshi AI, Ali Z,Suri MFK. Intraarterial third generation recombinant tissue plasminogen activator(reteplase) for acute ischemic stroke. Neurosurg 2001 Jul;49(1); 41-48.
Saver JL, Kidwell CS, Starkman S. Combined intravenous and intra-arterial tissue plasminogen activator for acute ischemic stroke: recanalization, safety, and early clinical outcome. Absract AAN 2001;S21.001
Suarez JI, Zaidat OO, Qureshi AI. Intra-arterial thrombolysis for patients with ischemic stroke presenting after 3 hours of symptom onset. Abstract AAN 2001 P06.101.