1. Rapid Sequence Intubation Drugs Ryan J. Fink, MD Raquel Bartz, MD Duke University Medical Center Dept. of Anesthesiology

2. Learning Objectives At the completion of this module the learner should be able to: – Choose the appropriate induction agent and neuromuscular blocking agent for a given clinical situation – Calculate the appropriate dose of both induction agent and paralytic for a given patient and clinical situation – Understand relative and absolute contraindications for induction agents and paralytics – Choose the appropriate vasopressor if blood pressure decreases after induction/intubation

3. Administration of General Anesthetics for Rapid Sequence Intubation

4. Induction Agents: General Principles Choice of agent dependent on: – Clinical status of the patient – Clinicians familiarity with the agent Timing - Anesthetic agent should: – Have time to take effect – Be given before paralysis

5. Primary concerns for agent choice: – Hemodynamic stability and risk of hypotension – Risk of additional respiratory depression – ICP and cerebral perfusion – History of ischemic heart disease – Rapidity of effect Secondary concerns for agent choice: – Amnestic properties – Emetic properties – Desired duration of effect Induction Agents: General Principles

6. Do no attempt intubation under suboptimal conditions! Patient is ready for intubation when: – Apneic – Unresponsive (no lid reflex) – Jaw is relaxed and mobile Induction Agents: General Principles

7. Ideal Induction Agent - Promote amnesia - Hemodynamic stability - Short-acting - Minimal Side Effects - Reversible - Metabolized independent of liver or kidney

8. Potential Induction Agents Etomidate Propofol Ketamine

9. Intravenous sedative hypnotic Used in original description of RSI Rapid bolus doses = severe hemodynamic instability NO LONGER A COMMON RSI AGENT Induction Drugs: Thiopental

10. Intravenous anesthetic Short-acting Hemodynamic response: – Minimal CV depression No major contraindications – Relative CI: adrenal insufficiency No analgesic activity Induction Agents: Etomidate

11. Intubating Dose: – 0.1 -0.2 mg/kg – i.e. 70 kg pt = 7 - 14 mg Onset of Action: < 1 min ( one arm-brain circulation ) T 1/2 : 10 – 20 min Hypnosis ( duration of action ): 3 - 5 min Side effects: – Myoclonus; burning – Nausea/vomiting – Reduce dose in the elderly – Adrenal suppression (inhibition of 11-beta- hydroxylation  reduced cortisol and aldosterone) Induction Agents: Etomidate

12. Intravenous anesthetic Short-acting Hemodynamic response: ↓SVR, contractility, and preload  often leading to ↓ BP No analgesic activity Contraindications: Hypotension, hypovolemia Induction Drugs: Propofol

13. Intubating Dose: – 1 - 2 mg/kg – i.e. 70 kg pt = 70 – 140mgmg Onset of Action: < 1 min ( one arm-brain circulation ) Hypnosis ( duration of action ): 3 - 5 min T 1/2 : 3 – 12 hours ( due to release from fat stores ) Side effects: – Burning at injection site – Some anti-emetic effect Induction Drugs: Propofol

14. Induction Drugs: Ketamine Intravenous sedative  dissociative anesthesia Structural analogue of phencyclidine Hemodynamic response: sympathetic stimulation  ↑ HR, contractility, SVR  ↑ BP + analgesic activity Contraindications: Increased BP dangerous; CAD

15. Induction Drugs: Ketamine Induction dose: – 1 - 2 mg/kg – 70 kg pt: 70 - 140 mg Onset of Action: < 1 min ( one arm-brain circulation ) Hypnosis ( duration of action ): 11 -17 min T 1/2 : 2 – 3 hours Side effects: – ↑ CBF, CMRO2, ICP – Nausea/vomiting – Excessive salivation – Hallucinations

16. Induction Agent Summary Mechanism of Action Intubating Dose (mg/kg) Onset (min) Duration of Hypnosis (min) Comments Etomidate ↑ GABA0.3< 13 - 5 - Adrenal suppression - CV stability - Nausea/vomiting Propofol ↑ GABA2 – 2.5< 13 - 5 - Causes hypotension - Burning at injection site Ketamine NMDA antagonist 2< 111 - 17 - Analgesia - ↑HR, SVR, BP, ICP - Preserves respiratory drive - Broncho-dilator

17. Neuromuscular Blocking Agents for Rapid Sequence Intubation

18. Neuromuscular Blocking Agents Advantages: – ↓forceful regurgitation of gastric contents – Relaxation oral-pharyngeal muscles Easy distraction of mandible and tongue Disadvantages: – Apnea – Oral-pharyngeal soft tissue collapse Available agents: – Succinylcholine – Rocuronium

19. Succinylcholine Depolarizing neuromuscular blocker – Two ACh molecules together – Binds to ACh receptor, opens channel – Muscles fasciculation Major Advantage: rapid onset, brief duration Major Disadvantage: side effects

20. Succinylcholine Intubating dose: 0.6 – 1 mg/kg IV – 70 kg pt: 42 - 70 mg Onset of action: 30 – 60 seconds T ½ : 10 – 15 minutes Metabolism: Plasma cholinesterase – 96% of pts have normal enzyme – Prolonged duration w/ atypical gene – Prolonged duration w/ conditions that ↓ PC Liver disease Pregnancy

21. Bradycardia in adults after 2 nd dose ↑ K+ (≈ 0.5 – 1.0 mEq/L) ↑ ICP ↑ Intraocular pressure ↑ Intra-gastric pressure ↑ Lower esophageal sphincter tone ↑ muscle tone in pts w/ myotonia congenita or dystrophica Myalgias Succinylcholine: Side Effects

22. Hyperkalemia (approx 5.5 mEq/L or above) Increased risk of hyperkalemia: Burns or massive tissue trauma Hemiparesis, spinal cord trauma Approx 24 hours after acute injury Neuromuscular disease, i.e. Guillain-Barre or ALS Disuse atrophy, intra-abdominal abscess Malignant hyperthermia Some fractures (due to fasciculations) Succinylcholine: Contraindications

23. Rocuronium Non-depolarizing neuromuscular blocker – Amino-steroid molecule – Competitive inhibition at ACh receptors – No muscle fasciculations Major Advantage: rapid onset, lack of side effects Major Disadvantage: duration of action

24. Rocuronium Intubating Dose: 1.2 mg/kg - 70 kg pt: 90 mg Onset of Action: 45 – 60 sec T 1/2 : 45 – 70 minutes Side effects: no significant SEs Contraindications - Predicted difficult airway, difficult ventilation - Liver disease can cause prolonged paralysis - Bromide hypersensitivity

25. Neuromuscular Relaxant Summary Intubating Dose (mg/kg) Onset of action (sec) Duration of Action (min) Side effectsContra-Indications Succinyl- choline 1 – 1.530 - 6010 - 15 -Bradycardia - ↑ K+ - ↑ intra- cranial, gastric, & ocular pressure - Myalgias -Hyperkalemia - Denervating disease - Burns, massive muscle injury - Malignant Hyperthermia Rocuronium1 – 1.245 - 6045 - 70 - none-Difficult airway - Liver disease (relative CI)

26. Drug Systemic Vascular Resistance Heart Rate Mean Arterial Pressure Cardiac Output Etomidate ↔↔↔↔ Propofol ↓↓↓ ↓ Ketamine ↓/↑↑↑ ↑ Hemodynamics & Vasopressors Adapted from Longnecker, 2008

27. Drug Systemic Vascular Resistance Heart Rate Mean Arterial Pressure Cardiac Output Etomidate ↔↔ ↔↔ Propofol ↓↓↓ ↓ Ketamine ↓/↑↑↑ ↑ Hemodynamics & Vasopressors Adapted from Longnecker, 2008

28. Hemodynamics & Vasopressors ↓ SVR = phenylephrine (50 – 100mcg boluses) ↓ HR= atropine (0.5 mg bolus) ↓ Contractility = epinephrine (10 – 100 mcg boluses) – Epinephrine if anaphylaxis suspected Continuous infusions may be necessary

29. RSI Drugs: Adjuncts Lidocaine – IV local anesthetic – Esp. patients with traumatic brain injury/↑ ICP – ↓ sympathetic response to laryngoscopy – Limited data/controversial – 1.5 mg/kg IV, 2 minutes before RSI – Minimal side effects

30. Rapid Sequence Induction Drugs: Summary Main drug classes for RSI – General anesthetic – Neuromuscular blocking agent – Vasopressor – Possibly lidocaine (for brain injury patients) Choice of drug depends on: – Clinical situation and patient co-morbidities – Clinical judgment