CHPPC Module 31, Section 1.5: Reversal/Antidote Pages
MODULE 31: SMART PUMPS & PRACTICAL TROUBLESHOOTING

Section 31.5: Quick Reference: Reversal/Antidote Pages

Actionable, high-speed clinical guides for managing infusion-related toxicities and emergencies.

SECTION 31.5

The Emergency Playbook: Antidotes & Reversal Agents

Your high-speed reference guide for when things go wrong.

31.5.1 The “Why”: Speed and Accuracy Under Extreme Pressure

In a medical emergency—a “Code Blue,” a “Rapid Response,” or a sudden, unexpected patient decline—time is the most critical and least available resource. In these moments of extreme pressure, you will not have the luxury of leisurely consulting a textbook or searching a drug information database. You must have the critical, life-saving information for key reversal agents stored in your immediate working memory, backed by a rapid-access reference tool that provides just the facts, without the fluff. This section is designed to be that tool. It is not a comprehensive pharmacology chapter. It is a series of “playbook” pages, each one dedicated to a specific antidote for a specific infusion-related emergency.

The format of each page is deliberately stark and action-oriented. It answers three fundamental questions you will face in a crisis: What is happening? What do I do right now? What do I watch out for? Your role as the pharmacist at the scene of an emergency is to be the calm, confident source of truth for medication administration. You are the one who will be asked, “What’s the dose of Narcan?” or “How fast do we give the lipid?” or “How do I dilute the phentolamine?” Hesitation or uncertainty in these moments can delay care. This quick-reference guide is designed to be your cognitive aid, your external brain, ensuring that you can provide accurate, life-saving information with speed and precision when it matters most.

Retail Pharmacist Analogy: The Emergency “Red Binder”

Imagine a fire extinguisher mounted on the wall of your pharmacy. You don’t read the detailed instruction manual when the building is on fire. You look at the three simple pictures on the side: 1. PULL the pin. 2. AIM the nozzle. 3. SQUEEZE the handle. It’s a high-speed, action-oriented guide for a high-stakes, low-frequency event.

Similarly, think about the “Red Binder” you might have under the counter. It doesn’t contain the full pharmacy law book. It contains the essential, “what-to-do-right-now” protocols for emergencies:

  • Armed Robbery: Step-by-step instructions on what to do and what not to do.
  • Patient Seizure: Simple steps for protecting the patient and when to call 911.
  • Hazardous Spill: The location of the spill kit and the immediate steps to take.

This section of the module is your clinical “Red Binder.” These are the fire extinguishers for specific toxicological emergencies. You should review them, understand them, and know where to find them in an instant. When the alarm bells are ringing, you won’t have time to read a chapter; you’ll need the three simple steps to put out the fire.

Naloxone (Narcan)

Opioid Overdose Reversal

WHEN TO USE: THE CLINICAL TRIAD

Use for known or suspected opioid toxicity presenting with the classic triad: 1. Respiratory Depression (RR <12), 2. CNS Depression (somnolence, unresponsiveness), and 3. Miosis (pinpoint pupils).

WHAT TO DO NOW: The Dosing Playbook

  1. FIRST, CALL FOR HELP. Announce a Rapid Response or Code Blue. Ensure airway support (bag-valve mask) is initiated.
  2. STANDARD ADULT DOSE (NON-ARREST):
    • Give 0.4 mg to 2 mg of naloxone via IV push. Can also be given IM or SC if no IV access is available.
    • Administer slowly (over 30 seconds) unless the patient is in full arrest.
    • Re-assess in 2-3 minutes. If no response or inadequate response, repeat the dose.
    • Titrate to an adequate respiratory rate (>12 breaths/min), not to full consciousness. The goal is breathing, not waking.
  3. THE NALOXONE INFUSION (The “Gotcha” Antidote):
    • When to Start: Consider an infusion if the patient required multiple bolus doses or if the overdose is from a long-acting opioid (e.g., methadone, extended-release oxycodone). The half-life of naloxone (30-90 min) is shorter than most opioids!
    • How to Dose: A common starting point is to calculate two-thirds of the initial bolus dose that was effective, and run that as an hourly infusion rate.
      Example: Patient responded to a total of 1.2 mg. Start an infusion at $1.2 text{ mg} times frac{2}{3} = 0.8 text{ mg/hr}$.
    • How to Mix: A standard concentration is 2 mg of naloxone in 500 mL of D5W or NS (4 mcg/mL).

QUICK PHARMACOLOGY: Mechanism of Action

Naloxone is a pure, competitive antagonist at mu, kappa, and delta opioid receptors. It has a very high affinity for the mu receptor, allowing it to physically displace opioid agonists like morphine or fentanyl from the receptor, thereby reversing their effects. It has no agonist activity of its own—in a person with no opioids in their system, it has essentially no effect.

CLINICAL PEARLS & PITFALLS
  • Precipitated Withdrawal: In a patient who is physically dependent on opioids, a large, rapid dose of naloxone will throw them into acute, severe withdrawal (pain, agitation, nausea, tachycardia, hypertension). This is why you titrate to breathing, not consciousness.
  • The Half-Life Mismatch: Naloxone wears off. The opioid that caused the overdose is likely still on board. The patient can and will become re-sedated. This is why patients require prolonged monitoring (at least 2-4 hours) after receiving naloxone.
  • “Just Enough”: The goal of reversal in a pain patient is not to reverse all analgesia, leaving them in agony. The goal is to restore adequate ventilation. Use the smallest effective dose.

Intravenous Lipid Emulsion (ILE) 20%

Local Anesthetic Systemic Toxicity (LAST) Reversal

WHEN TO USE: The Clinical Picture of LAST

Suspect LAST in any patient during or after the administration of a large volume of local anesthetic (e.g., epidural, nerve block) who develops sudden CNS or cardiovascular changes.
CNS Signs (often appear first): Agitation, confusion, metallic taste, tinnitus, circumoral numbness, seizures.
Cardiac Signs: Bradycardia, arrhythmias, hypotension, leading to cardiac arrest.

WHAT TO DO NOW: The Dosing Playbook (ASRA Guidelines)

  1. FIRST, CALL FOR HELP. Announce a Rapid Response or Code Blue. Stop the local anesthetic infusion. Manage the airway.
  2. PATIENT > 70 kg:
    • Bolus Dose: Give 100 mL of 20% ILE as a rapid IV push over 2-3 minutes.
    • Infusion: Immediately start an infusion of 200-250 mL of 20% ILE over 15-20 minutes.
  3. PATIENT < 70 kg (Use Lean Body Weight):
    • Bolus Dose: Give 1.5 mL/kg of 20% ILE as a rapid IV push over 2-3 minutes.
    • Infusion: Immediately start an infusion at a rate of 0.25 mL/kg/min.
  4. IF PATIENT REMAINS UNSTABLE:
    • You may repeat the bolus dose once or twice.
    • You may double the infusion rate to 0.5 mL/kg/min.

QUICK PHARMACOLOGY: The “Lipid Sink” Theory

The primary mechanism is thought to be the creation of an expanded lipid compartment within the plasma. Highly lipophilic drugs (like bupivacaine) are effectively “pulled” out of the cardiac and CNS tissues and sequestered in this intravascular lipid phase, reducing the amount of free drug available to cause toxicity. It acts as a “lipid sink” or “lipid shuttle.”

CLINICAL PEARLS & PITFALLS
  • Maximum Dose: Do not exceed a total cumulative dose of approximately 12 mL/kg.
  • Propofol is NOT a substitute! While propofol is formulated in a lipid emulsion, its concentration is too low (1%) and the hemodynamic effects of a large bolus would be disastrous. You must use 20% Intralipid.
  • Lab Interference: Administration of ILE will make blood samples milky and can interfere with many laboratory tests. Notify the lab that the patient has received lipid emulsion therapy.
  • Be Prepared: Your pharmacy should have a “LAST Rescue Kit” containing vials/bags of 20% ILE stored in areas where nerve blocks and epidurals are performed (e.g., OR, L&D, PACU). You need to know where these are.

Phentolamine (Regitine)

Vasopressor Extravasation Reversal

WHEN TO USE: The Clinical Picture of Extravasation

Use for the extravasation (leakage from the vein into surrounding tissue) of a potent vasoconstrictor, most commonly norepinephrine, but also phenylephrine or dopamine. Signs include pain, swelling, blanching, and coldness at the IV site.

WHAT TO DO NOW: The Dosing Playbook

  1. FIRST, STOP THE INFUSION. Leave the catheter in place for now. Notify the primary provider and nursing leadership immediately.
  2. PREPARE THE ANTIDOTE:
    • Withdraw 5 mg to 10 mg of phentolamine (typically one or two 5 mg/1 mL vials).
    • Dilute this dose in 10 mL of preservative-free Normal Saline.
  3. ADMINISTRATION (By MD or trained RN, per policy):
    • Using a small (25-gauge or smaller) needle, the diluted phentolamine is injected in small amounts (0.1-0.2 mL at a time) subcutaneously in a clockwise fashion around the entire ischemic, blanched area.
    • The goal is to infiltrate the entire affected area to counteract the vasoconstriction.
  4. TIMING IS CRITICAL. Phentolamine is most effective when administered within 12 hours of the extravasation event. The sooner, the better, to prevent tissue necrosis.

QUICK PHARMACOLOGY: Mechanism of Action

Phentolamine is a non-selective alpha-adrenergic antagonist. Vasopressors like norepinephrine cause intense local vasoconstriction by stimulating alpha-1 receptors on vascular smooth muscle. Phentolamine works by competitively blocking these receptors, leading to vasodilation, restoring blood flow to the ischemic tissue, and preventing cell death and necrosis.

CLINICAL PEARLS & PITFALLS
  • Know Where It Is: Your pharmacy must have a policy and a designated location for phentolamine. It is often stored in the main pharmacy refrigerator and/or in an “Extravasation Kit” in critical care ADCs. In an emergency, you must be able to locate it instantly.
  • Alternative Options: If phentolamine is unavailable, topical nitroglycerin paste or terbutaline subcutaneous injections have been used as alternatives, but phentolamine is the standard of care.
  • Don’t Forget Supportive Care: In addition to the antidote, applying a warm compress (NOT cold) can help with vasodilation and drug dispersal. The affected limb should also be elevated.
  • The “Why”: After the immediate event is managed, this is a major patient safety event. It should trigger an investigation. Why did it happen? Was it a poorly secured peripheral IV? Should this patient have had a central line? This is a critical learning opportunity for the institution.