CHPPC Module 36, Section 4: The Acute Stroke (TPA) Order Set
MODULE 36: COMMON ORDER SETS & PROTOCOL CONSULTS: A PHARMACIST’S GUIDE

The Acute Stroke (TPA) Order Set

Handling a “Code Stroke.” This section provides a masterclass on the TPA (Alteplase) protocol: running the exclusion checklist, weight-based dose calculation, and critical blood pressure management.

SECTION 36.4

The Acute Stroke (TPA) Order Set

From Clinical Gatekeeper to Clot Buster: The Pharmacist’s Role When Every Second Counts.

36.4.1 The “Why”: Time Is Brain

There is no medical specialty where the phrase “time is tissue” is more brutally true than in the treatment of acute ischemic stroke. When a blood clot lodges in an artery supplying the brain, the tissue downstream begins to die at a terrifying rate—approximately 1.9 million neurons are lost for every minute that blood flow is not restored. This is not a gradual decline; it is a rapid, irreversible cascade of cellular death. In this environment, the hospital’s response must be a model of choreographed, high-speed efficiency. The activation of a “Code Stroke” or the “TPA for Acute Ischemic Stroke” order set is the starting gun for this race against the clock.

Your role as the pharmacist during a Code Stroke is one of the most high-stakes, high-pressure responsibilities you will ever have. You are the final and most critical gatekeeper for the single most effective—and most dangerous—medication in the stroke arsenal: Alteplase (tPA), a potent thrombolytic agent that dissolves blood clots. When administered to the right patient within the narrow therapeutic window, tPA can be a miracle drug, reversing the symptoms of a devastating stroke in real-time. When administered to the wrong patient, it can be fatal, causing a catastrophic intracerebral hemorrhage.

This dual nature of tPA defines your role. You must be two things at once: an accelerator and a brake. You must work with lightning speed to review the patient’s profile, calculate the precise weight-based dose, and prepare the medication for administration, helping the team meet its goal of a “door-to-needle” time of less than 60 minutes. Simultaneously, you must be a meticulous and unflinching guardian of the safety checklist, running through the long list of inclusion and exclusion criteria with forensic precision. You are the final check that ensures this powerful weapon is being aimed at the right target. This section is your masterclass in performing this high-wire act with confidence, speed, and absolute accuracy.

Retail Pharmacist Analogy: The Final Release of a High-Risk Compound

Imagine your pharmacy has a contract to compound a highly specialized, extremely expensive, and notoriously unstable chemotherapy agent. The process is complex and fraught with peril. An error in dilution could render it inert. An error in calculation could be toxic. The final product has a shelf life of only 60 minutes once mixed.

The oncologist calls and says, “I have the patient here, we’re ready for the infusion now.” The clock starts.

  • The Checklist (The Brake): Before you even touch a vial, you pull out the mandatory, multi-page compounding checklist. You verify the patient’s height, weight, and BSA. You confirm today’s lab results (ANC, platelets). You run through a list of contraindications. You are the absolute, final gatekeeper. If even one item on the checklist is not met, the process stops. You are the brake.
  • The Calculation & Preparation (The Accelerator): Once the checklist is cleared, you move with speed and precision. You perform the complex dose calculation. You pull the correct vials. You reconstitute and dilute with practiced efficiency, knowing that every minute the drug sits on the counter, it is degrading. You are the accelerator.
  • The Final Release: You place the final, verified, and labeled bag in a special transport container. You have just performed a high-risk, time-sensitive task where you were simultaneously responsible for rigid adherence to a safety protocol and the rapid execution of a technical process.

Responding to a Code Stroke is the clinical equivalent of this process, but the 60-minute shelf life applies to the patient’s brain. You must be both the meticulous gatekeeper and the rapid accelerator, all at once.

36.4.2 Your Prime Directive: The tPA Inclusion/Exclusion Checklist

This is the heart of your role. Before you can even think about dosing, you must become the master of this checklist. When a Code Stroke is activated, your first action is to open the patient’s chart and begin running this mental (and often, physical or electronic) checklist. You are hunting for any absolute contraindication that would make tPA administration unacceptably dangerous. The primary risk you are trying to avoid is causing or worsening a bleed, especially an intracerebral hemorrhage (ICH).

The First and Most Important Exclusion: Is it a Bleed?

The very first step in any stroke workup is a non-contrast CT scan of the head. The purpose of this scan is to answer one question: Is there blood? The symptoms of an ischemic stroke (a clot) and a hemorrhagic stroke (a bleed) can be identical, but the treatments are polar opposites. Giving a clot-buster to a patient who is already bleeding in their brain is a fatal error.
Your Role: You must personally verify the final, official read of the head CT. Do not proceed until you have seen the radiologist’s report (or received a direct confirmation from the neurologist) that explicitly states: “No evidence of acute intracranial hemorrhage.”

Masterclass Table: The Alteplase (tPA) Safety Checklist
Category Criteria (The “Look Fors”) Pharmacist’s “Street Smarts” & Data Source
INCLUSION CRITERIA (Must meet ALL)
Diagnosis Diagnosis of Acute Ischemic Stroke (AIS) causing a measurable neurological deficit. This is a physician diagnosis, but you are confirming it in the chart.
Time of Onset Symptom onset was clearly defined and is less than 3 hours ago. (This can be extended to 4.5 hours for a select patient population, but 3 hours is the initial, hard cutoff). This is the single most important piece of history. Look for “Last Known Well” time in the ED or neurology note. If the patient woke up with symptoms, the onset is the time they went to bed.
Age Age ≥ 18 years. Check patient demographics.
ABSOLUTE EXCLUSIONS (Any ONE of these is a HARD STOP)
Hemorrhage Evidence of intracranial hemorrhage on pre-treatment head CT. VERIFY THE CT READ. Do not proceed without it.
Recent Bleeding / Trauma – Significant head trauma or prior stroke in the last 3 months.
– History of previous ICH.
– Active internal bleeding (e.g., GI bleed).		 Review the patient’s problem list, recent hospitalizations, and the history documented in the ED note.
Blood Pressure Sustained blood pressure > 185/110 mmHg despite treatment. Look at the ED vital signs flow sheet. Has the BP been consistently above this level? Have they tried to treat it with IV labetalol or nicardipine? If it remains high, tPA is contraindicated.
Anticoagulation – Current use of a direct thrombin inhibitor or direct factor Xa inhibitor (DOACs) with evidence of effect.
– INR > 1.7 or PT > 15 seconds (if on warfarin).
– Therapeutic dose of LMWH within the last 24 hours.		 This is your prime territory. Scour the medication history. Did they take their Eliquis this morning? Check the labs for a baseline INR and platelet count. If you have any suspicion of recent anticoagulant use, you must stop the process and clarify.
Lab Values Platelet count < 100,000/mm³. Check the CBC from the ED. This is an absolute cutoff.

36.4.3 The Dosing Playbook: The tPA Calculation and Administration

Once you have cleared the patient for treatment, you must move with speed and absolute precision to calculate and prepare the dose. There is zero room for error in this calculation.

The Dosing Protocol
  • Total Dose: $$0.9 , \frac{\text{mg}}{\text{kg}}$$
  • Maximum Total Dose: 90 mg (for any patient weighing ≥ 100 kg)
  • Administration:
    • Give 10% of the total dose as an IV bolus over 1 minute.
    • Infuse the remaining 90% of the total dose via an IV pump over 60 minutes.
The tPA Dosing and Infusion Playbook: A Worked Example

Scenario: A 75-year-old female is cleared for tPA for an acute ischemic stroke.
Patient Weight: 72 kg

  1. Step 1: Calculate the Total Dose

    $$0.9 , \frac{\text{mg}}{\text{kg}} \times 72 \text{ kg} = 64.8 \text{ mg}$$

    Total Dose = 64.8 mg (This is less than the 90mg max).

  2. Step 2: Calculate the Bolus Dose (10% of Total)

    $$64.8 \text{ mg} \times 0.10 = 6.48 \text{ mg}$$

    Bolus Dose = 6.5 mg (Round to nearest tenth). The nurse will give 6.5 mg via IV push over 1 minute.

  3. Step 3: Calculate the Infusion Dose (90% of Total)

    $$64.8 \text{ mg} \times 0.90 = 58.32 \text{ mg}$$

    Infusion Dose = 58.3 mg. This is the amount that will be infused over 60 minutes.

  4. Step 4: The “Waste” Step & Infusion Preparation (Critical Safety Check)

    Alteplase typically comes in 100 mg vials. You will reconstitute the 100 mg vial (usually with 100 mL of sterile water, yielding 1 mg/mL). The total volume is 100 mL.
    Your total dose is 64.8 mL (64.8 mg). You must first waste the excess drug from the bag/vial.

    $$100 \text{ mg} – 64.8 \text{ mg} = 35.2 \text{ mg to waste}$$


    After wasting, you are left with exactly 64.8 mg. You will hand the bolus dose (6.5 mg or 6.5 mL) to the nurse, and the remaining 58.3 mg (58.3 mL) will be the infusion bag. This “waste first” method is a critical safety check to prevent accidental overdose.

  5. Step 5: Calculate the Infusion Rate

    The remaining 58.3 mg (58.3 mL) needs to be infused over 60 minutes.

    The pump rate is therefore 58.3 mL/hr.

EHR Pharmacy Order Entry Simulation (tPA)

64.8 mg

6.5 mg over 1 min

58.3 mg over 60 min

Rate: 58.3 mL/hr

36.4.4 The Other Emergency: Blood Pressure Management

Managing blood pressure during a stroke code is as critical as the tPA itself. High blood pressure is a major risk factor for causing a hemorrhagic conversion (turning an ischemic stroke into a bleed) after tPA is given. Conversely, blood pressure that is too low can compromise perfusion to the penumbra (the area of the brain that is ischemic but not yet infarcted). The tPA order set will have a detailed, stand-alone section for BP management, and you must be able to verify it with the same speed and accuracy as the tPA itself.

Masterclass Table: The Stroke BP Management Playbook
Timeframe Blood Pressure Goal First-Line IV Agents & Dosing
BEFORE tPA Must be $$< 185/110 , \text{mmHg}$$
  • Labetalol: 10-20 mg IV push over 1-2 minutes. May repeat once.
  • Nicardipine Infusion: Start at 5 mg/hr, titrate up by 2.5 mg/hr every 5-15 min (max 15 mg/hr).
DURING & AFTER tPA
(First 24 hours)		 Must be maintained $$< 180/105 , \text{mmHg}$$

BP monitoring becomes very frequent (q15min for 2h, then q30min for 6h, then hourly).

  • Labetalol: 10 mg IV push, followed by an infusion at 2-8 mg/min.
  • Nicardipine Infusion: Start at 5 mg/hr, titrate to desired BP.
Pharmacist’s BP “Gotchas” during a Code Stroke
  • Check for Contraindications: Before verifying the labetalol, do a quick mental check. Does the patient have a heart rate < 60? Do they have a history of severe asthma or decompensated heart failure? If so, labetalol may be a poor choice, and you should advocate for nicardipine.
  • Anticipate and Prepare: When you get the Code Stroke page, you should immediately ensure that both labetalol vials and a nicardipine drip are readily available in the ED. The time to discover you are out of stock is not when the BP is 190/115 and the team is waiting to push tPA.
  • Communication is Key: In the heat of the moment, you can be a vital resource. A simple, “Just a reminder, we need to get that BP down below 185/110 before we can give the alteplase,” can be a critical safety check for the entire team.