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Rapid Sequence Intubation Drugs Ryan J. Fink, MD Raquel Bartz, MD Duke University Medical Center Dept. of Anesthesiology 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 Administration of General Anesthetics for Rapid Sequence Intubation 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 Induction Agents: General Principles • 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 • Do no attempt intubation under suboptimal conditions! • Patient is ready for intubation when: – Apneic – Unresponsive (no lid reflex) – Jaw is relaxed and mobile Ideal Induction Agent - Promote amnesia - Hemodynamic stability - Short-acting - Minimal Side Effects - Reversible - Metabolized independent of liver or kidney Potential Induction Agents Etomidate Propofol Ketamine Induction Drugs: Thiopental • Intravenous sedative hypnotic • Used in original description of RSI • Rapid bolus doses = severe hemodynamic instability • NO LONGER A COMMON RSI AGENT Induction Agents: Etomidate • Intravenous anesthetic • Short-acting • Hemodynamic response: – Minimal CV depression • No major contraindications – Relative CI: adrenal insufficiency • No analgesic activity Induction Agents: Etomidate • 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) T1/2: 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-betahydroxylation reduced cortisol and aldosterone) Induction Drugs: Propofol • Intravenous anesthetic • Short-acting • Hemodynamic response: ↓SVR, contractility, and preload often leading to ↓ BP • No analgesic activity • Contraindications: Hypotension, hypovolemia Induction Drugs: Propofol • 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 T1/2: 3 – 12 hours (due to release from fat stores) Side effects: – Burning at injection site – Some anti-emetic effect 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 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 T1/2: 2 – 3 hours Side effects: – – – – ↑ CBF, CMRO2, ICP Nausea/vomiting Excessive salivation Hallucinations Induction Agent Summary Mechanism Intubating Onset Duration of of Action Dose (min) Hypnosis (mg/kg) (min) Etomidate Propofol Ketamine ↑ GABA ↑ GABA NMDA antagonist 0.3 2 – 2.5 2 <1 <1 <1 3-5 3-5 11 - 17 Comments - Adrenal suppression - CV stability - Nausea/vomiting - Causes hypotension - Burning at injection site - Analgesia - ↑HR, SVR, BP, ICP - Preserves respiratory drive - Broncho-dilator Neuromuscular Blocking Agents for Rapid Sequence Intubation 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 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 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 Succinylcholine: Side Effects • • • • • • • Bradycardia in adults after 2nd 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: Contraindications • 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) 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 Rocuronium • Intubating Dose: 1.2 mg/kg - 70 kg pt: 90 mg • Onset of Action: 45 – 60 sec • T1/2: 45 – 70 minutes • Side effects: no significant SEs • Contraindications - Predicted difficult airway, difficult ventilation - Liver disease can cause prolonged paralysis - Bromide hypersensitivity Neuromuscular Relaxant Summary Intubating Dose (mg/kg) Succinylcholine Rocuronium 1 – 1.5 1 – 1.2 Onset of action (sec) 30 - 60 45 - 60 Duration of Action (min) 10 - 15 45 - 70 Side effects Contra-Indications -Bradycardia - ↑ K+ - ↑ intra- cranial, gastric, & ocular pressure - Myalgias -Hyperkalemia - Denervating disease - Burns, massive muscle injury - Malignant Hyperthermia - none -Difficult airway - Liver disease (relative CI) Hemodynamics & Vasopressors Drug Systemic Vascular Resistance Heart Rate Mean Arterial Pressure Cardiac Output Etomidate ↔ ↔ ↔ ↔ Propofol ↓↓ ↓ ↓↓ ↓ Ketamine ↓/↑ ↑↑ ↑↑ ↑ Adapted from Longnecker, 2008 Hemodynamics & Vasopressors Drug Systemic Vascular Resistance Heart Rate Mean Arterial Pressure Cardiac Output Etomidate ↔ ↔ ↔ ↔ Propofol ↓↓ ↓ ↓↓ ↓ Ketamine ↓/↑ ↑↑ ↑↑ ↑ Adapted from Longnecker, 2008 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 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 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