1. Pharmacologic Management of Rapid Sequence Intubation (RSI)
James Gibson, PharmD
PGY1 Pharmacy Practice Resident

2. Learning Objectives List the six P’s of RSI.
Discuss historical rationale for “LOADing” patients undergoing RSI.
Understand the rationale for use of one induction agent over another.
Identify the contraindications to succinylcholine administration and how to manage patients who are not candidates.

3. Rapid Sequence Intubation (RSI)
Induction of a patient using simultaneous
Sedatives
Rapid-acting paralytic agent
Goal: to avoid assisted ventilation due to elevated risk of aspiration
Un-fasted patient
Pharyngeal/laryngeal manipulation

4. The Six P’s of RSI Preparation Pre-oxygenation
Pretreatment and induction
Paralysis
Placement of the tube
Post-intubation management

5. Preparation Assess patient—difficult airway? IV access
Monitor (tele, pulse ox)
Gather:
Equipment for intubation
Post-intubation medication(s)
Pertinent patient history
Supplies for surgical airway (just in case!!)
Difficult airway: trauma, cervical collar, can you visualize the oral pharynx or just hard palate?; obstruction/obesity, neck mobility

6. Pre-Oxygenation Goals: Methods: Establish O2 reservoir
Maximize time for intubation
Prevent need for bag-mask ventilation
Methods:
3-5 minutes of 100% O2 via face mask
4 (or 8) vital capacity breaths on 100% O2
100% O2 for 3 minutes = acceptable O2 sats for ~8 min
4 vital capacity breaths = acceptable O2 sats for ~6 min

7. Pre-Oxygenation
Pre-oxygenation is complicated by comorbidities, body habitus (pregnancy), agitation or patient cooperation, and availability of equipment to deliver 100% oxygen.

8. Pretreatment
Goal:
Mitigate adverse physiologic reactions to intubation
Sympathetic “pressor response”
Bronchospasm
Increased intracranial pressure (ICP)
Muscle fasciculation
Begins 2-3 minutes PRIOR to induction/paralysis
“LOAD”
Not routinely done in practice
Pressor response—manipulation of airway increase BP and HR
small effect from succinylcholine administration

9. Pretreatment Lidocaine Opioid Atropine Defasciculating agent
Dose: 1.5 mg/kg IV
To prevent rise in ICP by
Preventing cough
Blunting pressor response
May reduce reactive bronchospasm in asthma
Lidocaine lowers ICP by:
preventing coughing, and
Blunts pressor response—though less effective than fentanyl
However, paralyzed patients cannot cough, so benefit is likely insignificant
Lidocaine may be added to albuterol to prevent bronchospasm in asthmatics—the added benefit of lidocaine is uncertain

10. Pretreatment Lidocaine Opioid Atropine Defasciculating agent
Fentanyl 3 mcg/kg IV
Provides analgesia
Lessens pressor response
Limits ICP increase
More effective than lidocaine

11. Pretreatment Lidocaine Opioid Atropine Defasciculating agent
Dose: 0.02 mg/kg
To prevent bradycardia caused by airway manipulation and succinylcholine
Historically used in pediatrics
May be more beneficial with repeated doses of succinylcholine (i.e. OR setting)
Laryngoscopy and intubation thought to cause vaso-vagal reflexbradycardia
Review found that bradycardia in RSI is usually clinically insignificant (i.e. with single doses of succinylcholine)
Benefit was mostly described in case series involving the OR setting where multiple doses of succs were given
Atropine may predispose to arrhythmias (i.e. not benign drug)

12. Pretreatment Lidocaine Opioid Atropine Defasciculating agent
Fasciculations occur in >90% of patients given succinylcholine
Muscle pain
Increase intragastric pressure  emesis
Increase ICP (?)
Prevention
Higher doses of succs (1.5 mg/kg vs 1 mg/kg)
Non-depolarizing NMB (1/10th of paralytic dose)

13. Induction Agent(s)
Given as rapid IV push immediately before paralyzing agent
Ideally provides:
Rapid loss of consciousness
Analgesia
Amnesia
Stable hemodynamics
Induction agents also provide relaxation, which is additive to that of NMBA’s

14. Induction Agents Drug Dose Thiopental 3-5 mg/kg IV Methohexital
Fentanyl
5-15 mcg/kg IV
Midazolam
0.1 mg/kg IV
Ketamine
1-2 mg/kg IV
Etomidate
0.3 mg/kg IV
Propofol
2 mg/kg IV

15. Induction Agents Etomidate Ultrashort-acting non-barbiturate hypnotic
Rapid onset—30 to 60 secs
Hemodynamic stability
Hydrolyzed in liver and plasma
 ICP with minimal effects on cerebral perfusion
NO analgesia
ADE: Myoclonic jerks,  cortisol production
Myoclonic jerks can be confused with seizure activity, but just disinhibition of subcoritcal activity.
Prevented by NMB, thus rarely seen in RSI.
No treatment needed; can use benzo if persistent.
Infusions of etomidate have been associated with adrenal suppression and strongly linked to increased mortality in critically ill patients.
Suppression after single dose has been inconsistently demonstrated, and significance of mild cortisol suppression in septic shock is uncertain.

16. Induction Agents Fentanyl Short-acting, potent
Minimal histamine release
Hemodynamically stable
Sedation is rate- AND dose-dependent
Combined with other induction agents for analgesia
ADE: muscle rigidity, grand mal seizures (rare)
No histamine release = no hypotension or emesis
Chest wall rigidity  difficult bag ventilation. But NMBA obviates clinical significance of this.

17. Induction Agents Midazolam Sedative, amnestic, muscle relaxant
NOT analgesic
Less cardiorespiratory depression vs. other benzos
BP; HR
Use lower dose in hypovolemic, elderly, or traumatic brain injury patients (0.05 mg/kg)
Does NOT contain propylene glycol
Propylene glycol toxicity  acute renal failure, lactic acidosis, osmol gap
Solubilizing agent in lorazepam IV

18. Induction Agents Ketamine NMDA-antagonist  dissociative anesthesia
Analgesic, amnestic, anesthetic
Dissociation occurs at threshold of mg/kg IV
4-5 mg/kg IM (more emesis)
Catecholamine reuptake inhibition ( HR, BP, CO, ICP)
Maintains respiration and airway reflexes
ADE: Emergence delirium (30%)—Premed: midazolam 0.07 mg/kg
Emesis (highest in adolescents ~9yo)
CI: schizophrenia (schizoaffective); <3 months
(relative): Asthma exacerbation; CVD
Produces a cataleptic-like state; dissociated from the surrounding environment by direct action on the thalamocortical and limbic systems.
Noncompetitive NMDA receptor antagonist that blocks glutamate.
Eyes often remain open, and patient may make spontaneous, non-purposeful movements
CV effects may make it useful in patients w/ hemorrhagic shock
~1/3 of patient have emergence reaction. Less common in children + midaz does not seem to decrease incidence in children.
Annals of Emergency Medicine (2011):

19. Neuromuscular Blocking Agents (NMBAs)
Quaternary ammonium compounds that mimic structure of ACh
Depolarizing vs non-depolarizing
Allow complete airway control
Higher success (100% vs 82%)
Less aspiration and airway trauma
Enable lower doses of sedative
Better hemodynamic stability
Acetylcholine
Succinylcholine
Roberts: Clinical Procedures in Emergency Medicine. 5th.
Philadelphia, PA: Elsevier,

20. Succinylcholine Depolarizing NMBA Paralysis in ~60 sec. DOA: 3-5 min
Non-competitively binds ACh receptors  initial membrane depolarization
Longer degradation time than ACh
Paralysis in ~60 sec. DOA: 3-5 min
Prolonged in pseudocholinesterase deficiency (genetic, hepatic/renal failure, pregnancy, cocaine)
Repeat doses prolong paralysis
May increase bradycardia/hypotension
DOC for RSI
Duration varies by resource—some state up to 6-10 minutes.
Pseudocholinesterase deficiency may prolong to 23 minutes in severe cases

21. Succinylcholine Dose: 1.5 mg/kg IV (infants: 2 mg/kg IV) ADEs:
Use ACTUAL body weight
Rapid bolus; follow w/ mL saline flush
ADEs:
Muscle fasciculation  myalgias
Hyperkalemia,  CPK
Bradycardia/hypotension
Mild increase in ICP
Malignant hyperthermia
Malignant hyperthermia: rare, hereditary complication—autosomal dominant
Fever, tacypnea, tachycardia, arrhythmias, acidosis, muscle rigidity, impaired coagulation
Treat with cooling, volume repletion, and Dantrolene sodium (1-2 mg/kg IV)

22. Succinylcholine Hyperkalemia Typical K+ increase < 0.5 mEq/L
Up to a 5 mEq/L K+ increase in certain settings:
Contraindicated in:
Conditions with up-regulation of ACh-receptors (see table)
Known/suspected hyperkalemia
Personal/family hx of malignant hyperthermia
Hyperkalemia is NOT prevented by defasciculating doses of non-depolarizing NMBAs
Clinically, safer to consider period of concern >72 hours (or 3 days)
Myasthenia Gravis is NOT a contraindication—actually require higher doses of succinylcholine (2 mg/kg)

23. Non-Depolarizing NMBAs
Competitive antagonists of ACh at neuromuscular junctions
Higher doses = faster onset, longer duration
Reversible
Alternatives to succinylcholine
Long-acting vs intermediate-acting
Agent
Dose (mg/kg)
Onset (min)
Duration (min)
Succinylcholine
1.5 1
3-5
Rocuronium
1-1.5
30-110
Vecuronium
0.1
0.25 3
30-35
60-120
Pancuronium
2-5
(60-100)
Neostigmine: mg/kg IV; Max of 5 mg in adults (depending on reference)
Will reverse NMBA’s action only after ~40% of effects have worn off (UpToDate)
Give with atropine to block systemic cholinergic response (0.5-1mg)
Sugammadex is an investigational agent for reversal of non-depolarizing agents
Roberts: Clinical Procedures in Emergency Medicine. 5th.
Philadelphia, PA: Elsevier,

24. Non-Depolarizing NMBAs
Pancuronium
Long time to onset
 HR and BP (vagolytic effect)
Histamine release  bronchospasm/anaphylaxis
Active metabolites
Accumulates
Renal dosing required
NOT recommended for RSI
Binds muscarinic receptors in SA node and prevents uptake
Renally cleared, so accumulates with renal insufficiency
CrCl 10-50: 50% of dose
CrCl <10: do not administer

25. Non-Depolarizing NMBAs
Vecuronium
Slower onset than rocuronium
Non-vagolytic; no histamine release
Active metabolites
Often requires “priming” dose
0.01 mg/kg during pre-oxygenation phase, then
1.5 mg/kg given 3 min later for paralysis

26. Non-Depolarizing NMBAs
Rocuronium
Onset similar to succinylcholine
Non-vagolytic; no histamine release
No active metabolites
Preferred alternative to succinylcholine in RSI

27. Post-intubation Care After endotracheal tube is placed:
Provide continued sedation/analgesia
Propofol drip (No analgesia)
≤ 120 kg begin infusion at 20 mcg/kg/min
kg begin infusion at 15 mcg/kg/min
>151 kg begin infusion at 10 mcg/kg/min
Bolus fentanyl and midazolam
Fentanyl (analgesia):
LD: mcg IV q15 min PRN (max 300 mcg in first hr)
MD: mcg IV q30 min PRN (max 200 mcg/hr)
Midazolam (sedation):
LD: 1-4 mg IV q15 min PRN (max 16 mg in first hr)
MD: 1-4 mg IV q1 hr PRN
UWMC Form U2914

28. References
Claudius, C, LH Garvey, J Viby-Mogensen, et al. "The Undesirable Effects of Neuromuscular Blocking Drugs." Anaesthesia (2009): Print.
Fleming, Bethany, Maureen McCollough, et al. "Myth: Atropine should be administered before succinylcholine for neonatal and pediatric intubation.." Can J Emerg Med. 7.2 (2005): Print.
Green, Steven, Mark Roback, et al. "Clinical Practice Guidelines for Emergency Department Ketamine Dissociative Sedation: 2011 Update." Annals of Emergency Medicine (2011): Print.
Hopson, Laura, and Richard Schwartz. Roberts: Clinical Procedures in Emergency Medicine. 5th. Philadelphia, PA: Elsevier, Print.
Martyn, Jeevendra, and Martina Richtsfeld. "Succinylcholine-induced Hyperkalemia in Acquired Pathologic States." Anesthesiology (2006): Web. 8 Mar
Walls, Ron. Marx: Rosen's Emergency Medicine. 7th ed. Philadelphia, PA: Elsevier, Print.