3.9 Neuromuscular Reversal & Vasoactive Airway Support

3.9 Neuromuscular Reversal & Vasoactive Airway Support

Emergency Rapid Sequence Induction (RSI) induces profound physiological stress. Transport clinicians must manage neuromuscular blockade reversal during emergency airway failures and administer push-dose vasopressors to prevent post-intubation hemodynamic collapse.

---

1. Neuromuscular Blockade Reversal Agents

Reversal of non-depolarizing neuromuscular blocking agents (NMBAs) is indicated when a patient cannot be intubated or ventilated, or when extubation criteria are met following transport.

                    NEUROMUSCULAR REVERSAL MECHANISMS

  Sugammadex Encapsulation:            Neostigmine AChE Inhibition:
   +-------------+                     +-----------------------+
   | Sugammadex  |                     | Neostigmine Blocks    |
   | Ring        |                     | Acetylcholinesterase  |
   |  +-------+  |                     +-----------+-----------+
   |  | Rocur |  |                                 |
   |  +-------+  |                     [ Increased Synaptic ACh ]
   +-------------+                                 |
   (Inactivated Complex Excreted)      [ Competes with NMBD at NMJ ]
                                                   +
                                       [ MUST Add Glycopyrrolate ]
                                       (Prevents Severe Muscarinic Effects)

A. Sugammadex (Bridion)

Sugammadex is a modified $\gamma$-cyclodextrin designed to selectively encapsulate aminosteroid NMBAs (Rocuronium and Vecuronium).

• Mechanism of Action: Forms a lipophilic core complex with free Rocuronium in plasma at a $1:1$ ratio, rapidly lowering free drug concentration and driving the NMBA away from the neuromuscular junction (NMJ) back into plasma.
• Dosing Tiers:
  • $2 \text{ mg/kg}$ IV: Routine reversal of shallow blockade (reappearance of $T_2$ twitch on Train-of-Four [TOF]).
  • $4 \text{ mg/kg}$ IV: Reversal of deep blockade ($1-2$ post-tetanic counts [PTC] with zero TOF twitches).
  • $16 \text{ mg/kg}$ IV: Immediate emergency rescue reversal following high-dose Rocuronium ($1.2 \text{ mg/kg}$) RSI in a "Cannot Intubate, Cannot Ventilate" scenario. Reverses blockade within $3 \text{ minutes}$.
• Drug Interactions & Warnings:
  • Binds to oral contraceptives, decreasing their efficacy (equivalent to missing 1 daily dose; patients must use barrier contraception for 7 days).
  • Ineffective against Succinylcholine or benzylisoquinoliniums (Cisatracurium, Atracurium).

B. Neostigmine + Anticholinergic Co-Administration

Neostigmine is a traditional acetylcholinesterase (AChE) inhibitor.

• Mechanism of Action: Inhibits breakdown of acetylcholine (ACh) in the synaptic cleft, elevating ACh concentration to outcompete non-depolarizing NMBAs at nicotinic receptors.
• Dosing: Neostigmine $0.03 - 0.07 \text{ mg/kg}$ IV (maximum single dose $5 \text{ mg}$). Requires at least partial spontaneous recovery ($T_2$ visible on TOF); ineffective for immediate rescue from deep paralysis.
• Mandatory Anticholinergic Co-Administration: Acetylcholinesterase inhibition elevates ACh at both nicotinic and muscarinic receptors, causing severe bradycardia, AV block, bronchospasm, hyper-salivation, and bronchorrhea. Neostigmine must always be co-administered with an anticholinergic:

---

2. Peri-Intubation Hemodynamic Optimization & Push-Dose Pressors

Induction and positive pressure ventilation frequently trigger severe hypotension. Peri-intubation cardiac arrest occurs in up to $2-4%$ of emergency intubations, driven primarily by profound post-induction hypotension.

                 PATHOPHYSIOLOGY OF POST-INTUBATION HYPOTENSION

  Induction Agents (Propofol/Midazolam) ---> Vasodilation + Sympatholysis
                                                  |
  Positive Pressure Ventilation         ---> High Intra-thoracic Pressure
                                                  |
  Decreased Venous Return (Preload)     ---> DROPPED CARDIAC OUTPUT
                                                  |
                                        [ SEVERE HYPOTENSION ]

Push-Dose Vasopressor Protocols

Push-dose pressors provide immediate temporizing vasopressor support during the peri-intubation window while continuous infusions are prepared.

                      PUSH-DOSE PRESSOR MIXING GUIDE

  Phenylephrine (100 mcg/mL):            Epinephrine (10 mcg/mL):
  1. Take 1 mL Phenylephrine (10 mg/mL)  1. Take 1 mL Epi 1:10,000 (100 mcg/mL)
  2. Inject into 100 mL NS bag           2. Draw up into syringe with 9 mL NS
  3. Yields 100 mcg/mL                   3. Yields 10 mcg/mL ("Dirty Epi")
  4. Dose: 50-200 mcg (0.5-2 mL)         4. Dose: 5-20 mcg (0.5-2 mL)

A. Push-Dose Phenylephrine

• Pharmacology: Pure $\alpha_1$-adrenergic receptor agonist causing arterial vasoconstriction and increased Systemic Vascular Resistance (SVR).
• Mixing Protocol: Draw $1 \text{ mL}$ of Phenylephrine ($10 \text{ mg/mL} = 10,000 \text{ mcg}$) and inject into a $100 \text{ mL}$ bag of Normal Saline. Concentration $= 100 \text{ mcg/mL}$.
• Dosing: Administer $50 - 200 \text{ mcg}$ ($0.5 - 2.0 \text{ mL}$) IV/IO every $2-5 \text{ minutes}$.
• Onset & Duration: Onset $1 \text{ minute}$; duration $10-20 \text{ minutes}$.
• Best Clinical Indication: Pure vasodilatory hypotension with normal or elevated baseline heart rate (causes reflex bradycardia).

B. Push-Dose Epinephrine

• Pharmacology: Direct $\alpha_1$, $\beta_1$, and $\beta_2$-agonist providing potent vasoconstriction, inotropy, chronotropy, and bronchodilation.
• Mixing Protocol: Take $1 \text{ mL}$ of Epinephrine $1:10,000$ ($100 \text{ mcg/mL}$) in a syringe and add $9 \text{ mL}$ of Normal Saline. Concentration $= 10 \text{ mcg/mL}$.
• Dosing: Administer $5 - 20 \text{ mcg}$ ($0.5 - 2.0 \text{ mL}$) IV/IO every $2-5 \text{ minutes}$.
• Onset & Duration: Onset $1 \text{ minute}$; duration $5-10 \text{ minutes}$.
• Best Clinical Indication: Post-induction hypotension accompanied by bradycardia, profound myocardial depression, or septic/anaphylactic shock.

---

3. Resuscitation Prior to Intubation

To prevent the "HOP" kill spikes (Hypotension, Oxygenation deficit, PH/Acidosis) during RSI:

1. Pre-Intubation Volume Loading: Administer $500 - 1,000 \text{ mL}$ crystalloid or blood products prior to induction in hypovolemic patients.
2. Hemodynamically Neutral Induction: Utilize Ketamine ($1.5-2.0 \text{ mg/kg}$ IV) or Etomidate ($0.3 \text{ mg/kg}$ IV) rather than Propofol ($1.5-2.5 \text{ mg/kg}$) or Midazolam ($0.1-0.2 \text{ mg/kg}$), which cause severe venodilation and myocardial depression.