Pharmacologic Management of Rapid

Sequence Intubation (RSI)James Gibson, PharmD

PGY1 Pharmacy Practice Resident

Learning ObjectivesList 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.

Rapid Sequence Intubation (RSI)

Induction of a patient using simultaneousSedativesRapid-acting paralytic agent

Goal: to avoid assisted ventilation due to elevated risk of aspirationUn-fasted patientPharyngeal/laryngeal manipulation

The Six P’s of RSIPreparation

Pre-oxygenation

Pretreatment and induction

Paralysis

Placement of the tube

Post-intubation management

PreparationAssess patient—difficult airway?

IV access

Monitor (tele, pulse ox)

Gather:Equipment for intubationPost-intubation medication(s)Pertinent patient historySupplies for surgical airway (just in case!!)

Pre-OxygenationGoals:

Establish O2 reservoirMaximize time for intubationPrevent need for bag-mask ventilation

Methods:3-5 minutes of 100% O2 via face mask

4 (or 8) vital capacity breaths on 100% O2

Pre-Oxygenation

http://www.ncsrc.org/2_newsletters_2008_2.shtml

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

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

Pretreatment Lidocaine

Opioid

Atropine

Defasciculating agent

Fentanyl 3 mcg/kg IV

Provides analgesia

Lessens pressor response Limits ICP increase More effective than lidocaine

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)

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)

Induction Agent(s)Given as rapid IV push immediately before paralyzing agent

Ideally provides:Rapid loss of consciousnessAnalgesiaAmnesiaStable hemodynamics

Induction Agents

Drug Dose

Thiopental 3-5 mg/kg IV

Methohexital 1-3 mg/kg IV

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

Induction AgentsEtomidate

Ultrashort-acting non-barbiturate hypnoticRapid onset—30 to 60 secsHemodynamic stabilityHydrolyzed in liver and plasma ICP with minimal effects on cerebral perfusionNO analgesiaADE: Myoclonic jerks, cortisol production

Induction AgentsFentanyl

Short-acting, potentMinimal histamine releaseHemodynamically stableSedation is rate- AND dose-dependentCombined with other induction agents for analgesiaADE: muscle rigidity, grand mal seizures (rare)

Induction AgentsMidazolam

Sedative, amnestic, muscle relaxantNOT analgesic

Less cardiorespiratory depression vs. other benzosBP; HR

Use lower dose in hypovolemic, elderly, or traumatic brain injury patients (0.05 mg/kg)

Does NOT contain propylene glycol

Induction AgentsKetamine

NMDA-antagonist dissociative anesthesiaAnalgesic, amnestic, anesthetic

Dissociation occurs at threshold of 1-1.5 mg/kg IV4-5 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

Annals of Emergency Medicine. 57.5 (2011): 449-461

Neuromuscular Blocking Agents (NMBAs)

Quaternary ammonium compounds that mimic structure of AChDepolarizing vs non-depolarizing

Allow complete airway controlHigher success (100% vs 82%)Less aspiration and airway trauma

Enable lower doses of sedativeBetter hemodynamic stability

Roberts: Clinical Procedures in Emergency Medicine. 5th.Philadelphia, PA: Elsevier, 2010. 99-109

Acetylcholine

Succinylcholine

SuccinylcholineDepolarizing NMBA

Non-competitively binds ACh receptors initial membrane depolarization

Longer degradation time than ACh

Paralysis in ~60 sec. DOA: 3-5 minProlonged in pseudocholinesterase deficiency (genetic,

hepatic/renal failure, pregnancy, cocaine)Repeat doses prolong paralysis

May increase bradycardia/hypotension

DOC for RSI

SuccinylcholineDose: 1.5 mg/kg IV (infants: 2 mg/kg IV)

Use ACTUAL body weightRapid bolus; follow w/ 20-30 mL saline flush

ADEs:Muscle fasciculation myalgias

Hyperkalemia, CPKBradycardia/hypotensionMild increase in ICPMalignant hyperthermia

SuccinylcholineHyperkalemia

Typical K+ increase < 0.5 mEq/LUp 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

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 1-1.5 30-110

Vecuronium 0.10.25

31

30-3560-120

Pancuronium 0.1 2-5 (60-100)Roberts: Clinical Procedures in Emergency Medicine. 5th.Philadelphia, PA: Elsevier, 2010. 99-109

Non-Depolarizing NMBAsPancuronium

Long time to onset HR and BP (vagolytic effect)Histamine release bronchospasm/anaphylaxisActive metabolitesAccumulates

Renal dosing required

NOT recommended for RSI

Non-Depolarizing NMBAsVecuronium

Slower onset than rocuroniumNon-vagolytic; no histamine releaseActive metabolitesOften requires “priming” dose

0.01 mg/kg during pre-oxygenation phase, then1.5 mg/kg given 3 min later for paralysis

Non-Depolarizing NMBAsRocuronium

Onset similar to succinylcholineNon-vagolytic; no histamine releaseNo active metabolites

Preferred alternative to succinylcholine in RSI

Post-intubation CareAfter endotracheal tube is placed:

Provide continued sedation/analgesiaPropofol drip (No analgesia)

≤ 120 kg begin infusion at 20 mcg/kg/min 121-150 kg begin infusion at 15 mcg/kg/min >151 kg begin infusion at 10 mcg/kg/min

Bolus fentanyl and midazolam Fentanyl (analgesia):

LD: 25-100 mcg IV q15 min PRN (max 300 mcg in first hr)MD: 25-100 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

References Claudius, C, LH Garvey, J Viby-Mogensen, et al. "The Undesirable Effects of

Neuromuscular Blocking Drugs." Anaesthesia. 64.1 (2009): 10-21. 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): 114-117. Print.

Green, Steven, Mark Roback, et al. "Clinical Practice Guidelines for Emergency Department Ketamine Dissociative Sedation: 2011 Update." Annals of Emergency Medicine. 57.5 (2011): 449-461. Print.

Hopson, Laura, and Richard Schwartz. Roberts: Clinical Procedures in Emergency Medicine. 5th. Philadelphia, PA: Elsevier, 2010. 99-109. Print.

Martyn, Jeevendra, and Martina Richtsfeld. "Succinylcholine-induced Hyperkalemia in Acquired Pathologic States." Anesthesiology. 104. (2006): 158-69. Web. 8 Mar. 2012.

Walls, Ron. Marx: Rosen's Emergency Medicine. 7th ed. Philadelphia, PA: Elsevier, 2010. 3-22. Print.