Managing “Anesthesia” in Radiology Local anesthesia to conscious sedation Collan Simmons, B.Sc., M.D. PGY-5 Anesthesia (Anisa’s husband)

Warm Up Questions What are you typical doses of Fentanyl? Midazolam? What is the name of the antidote for benzodiazepines? Maximum dose of lidocaine (/kg)? With Epi?

Objectives Basics of Sedations Local Anesthesia Monitors & Support Opioids Benzodiazepines Local Anesthesia Toxicities & Management

What you need before you start Sedation What you need before you start

Monitors Required: Suggested Oxygen Saturation/HR Blood pressure ECG Tells you about oxygenation (not ventilation) Blood pressure Suggested ECG Respiratory Rate

Sedation Basics IV access Oxygen Backup Equipment Nasal prongs (Fi02 = 30% max) Face mask (Fi02 = 50% max) Backup Equipment IV fluids Self-inflating resuscitation bag Oral/Nasal Airways Antidotes

Fasting Guidelines: Any procedure that may require IV sedation: 8 hours after a meal that includes meat, fried or fatty foods 6 hours after a light meal (such as toast and a clear fluid), or after ingestion of infant formula or nonhuman milk 4 hours after ingestion of breast milk 2 hours after clear fluids.

Sedative Agents

Sedation Goals Analgesia Anxiolysis +/-Amnesia Intra-procedural vs long acting Anxiolysis +/-Amnesia Return to baseline shortly after procedure

Ideal Properties of Sedative Agents Titratable Fast Onset Short duration Wide therapeutic index Minimal Side effects Antidote/Reversal Agent available

Sedation Typical Agents Used Opioids Benzodiazepines Propofol

Propofol Titratable Amnesia Sedation No analgesia Fast Onset Short duration Amnesia Sedation No analgesia

} Propofol NARROW Therapeutic index Hemodynamics: Sedation Apnea Loss of airway reflexes Loss of consciousness Hemodynamics: Direct myocardial depressant Vasodilator }

= Best left to Anesthesia Propofol Prior to use Ready for general anesthesia A/W control Possible ventilation Ready for hemodynamic consequences Fluids Short acting vasoactive agents = Best left to Anesthesia

Opioids

Opioids Common Drugs Fentanyl Morphine Hydromorphone

Opioids Good Characteristics Bad Characteristics Analgesia Respiratory depression Pruritus Nausea

Fentanyl Synthetic opioid 100X more potent than morphine Fast onset Highly lipid soluble Minimal pruritus, nausea 100X more potent than morphine Fast onset No active metabolites Clinically effective for approximately 30 min dose dependent

Fentanyl Supplied as: Dosing: (by ideal weight) Onset 50 mcg/ml (equivalent in potency to 5 mg morphine)‏ Dosing: (by ideal weight) Sedation: 0.5 – 1 mcg/kg, titrated to effect 50kg Woman: 25 -50 mcg 80kg Man: 50-100 mcg Induction of Anesthesia: Typical: 1-3 mcg/kg Cardiac: 5-10 mcg/kg Onset Subjective: 1 min Peak effect: 5 min

Fentanyl Elimination half life Clinical half life Surprisingly long T ½ = 3.1 - 6.6h Morphine = 1.7 - 3.3h Hepatic elimination Clinical half life Short because of distribution (highly lipid soluble)

Elimination vs. Distribution Rapid onset: IV injection  vessel rich group –(BBB) CNS Termination clinical effect is due to Washout from brain Distribution to clinically irrelevant tissues (muscle, fat) Plasma concentration falls below threshold Elimination Exceptions to the above: Repeat doses (fill up the inactive tissues) Large doses Cardiac Surgery Infusions ICU

Fentanyl & Organ Failure Hepatic Inactivated by hepatic metabolism dependent on hepatic blood flow elderly Reduce dose, but still safe Renal Inactive metabolites excreted via kidneys

Side effects: Nausea, Vomiting, Constipation…

Side effects: Depressed level of consciousness Respiratory Depression Airway reflexes Aspiration (fasted) Respiratory Depression Dose dependent decrease in respiratory rate Hypoventilation Hypercarbia Hypoxia

Side effects: Cardiovascular No direct myocardial depressant effects No direct vasodilating effects BUT: Does decrease patients sympathetic outflow Decr HR Decr BP Decr vascular tone

Patients to be WEARY of: Prone to respiratory depression, desaturation COPD Sleep Apnea Obesity Hypovolemic/Critically Ill Limited distribution of drug = “sensitive” More likely to experience apnea and hypotension Elderly Decreased reserve, hepatic blood flow Slow “arm-brain” time  be patient in dosing

Initial Treatment of (Serious) Opioid Side Effects Respiratory Depression: Airway & Breathing (Oxygen already on) Upgrade to FM Stimulate patient/check resp rate Adjust upper airway (jaw thrust) Look for respiratory effort (?obstruction) Oral A/W, Jaw thrust Bag Mask Ventilation (100% O2) Antidote

Naloxone (Narcan) Narcotic antagonist Supplied as 0.4 mg in 1 cc Route: IV, SC, IM, (ETT) Onset: <2 min Dose: ER: 0.4mg IV, double every 2-3min until desired LOC/RR achieved Reserve for RR = 0. ACUTE REVERSAL OF ANALGESIA Selective reversal: dilute 0.4 mg to total of 10cc = 0.04 mg/cc 1st dose = 0.04mg IV, double q 2min until desired LOC/RR achieved Rarely need to give more than 2-3 doses Elimination half-life: 60-90min Shorter that most opioid elimination half-lives May need repeat doses or infusion

Fentanyl Summary Short-acting, potent analgesic Termination of effect by distribution Only redose after enough time for peak effect 5 min Dose dependent respiratory depression Oxygen for all patients Keep an eye on the RR Simple A&B’s will get you out of most trouble Narcan

Be patient in your dosing: You can always give some more, but you can’t take a big dose back

Benzodiazepines

Benzodiazepines Anterograde Amnesia Anxiolysis Anticonvulsant properties Somnolence/Hypnotic No analgesia

Typical Benzos Midazolam Diazepam Lorazepam

Midazolam Water soluble 2x more potent than diazepam Amnesia > Sedation Route: IV, IM, PO, IN Supplied as: 1 mg/ml 5 mg/ml Oral preparation (facility dependent, 2mg/ml)‏ Onset: IV: 30 - 60s Peak: 3 - 5 min

Midazolam Dosing: IV 0.5 – 2.5 mg aliquots 5 min between doses (allow peak effect) Duration: 15 - 85 min

Midazolam Duration Elimination Metabolites Distribution to/from brain Rapid hepatic clearance Elimination Half-time 1-4 h Doubled in elderly Metabolites Partially active (50%), rapidly cleared via kidneys

Midazolam & Organ Failure Hepatic Metabolism dependent on hepatic blood flow and enzyme activity Elderly, liver failure Reduce dose, but still safe Faster metabolism than other benzos Renal Not affected by renal failure Caveat: renal failure + infusion (ICU setting)

Midazolam Side Effects Depressed level of consciousness Ventilation Depressed airway reflexes Ventilation Decrease hypoxic drive (COPD) Midazolam as sole agent Minimal respiratory depression (unless COPD or elderly) Synergism with other agents Worsen respiratory depression of fentanyl More significant than diazepam/lorazepam

Midazolam Side Effects Cardiovascular Decr BP Incr HR CO maintained

Diazepam “Valium” ½ as potent as midazolam Long elimination time 21-37h Directly proportional with age Active metabolites Renal excretion: even longer elimination half-life Organ failure Hepatic: prolonged elimination Renal: prolonged elimination

Lorazepam 3x as potent as midazolam PO, SL, IV, IM Slow peak effects (20-30 minutes) Long clinical effects (6-10 hours) More potent sedative and amnestic Long elimination time 10-20 hours Non-active metabolites, no adjustments for organ failure

Benzodiazepines Most common side effects: Prolonged sedation Respiratory depression COPD Elderly ... synergistic with other CNS depressants Opioids etc.

Initial Treatment of (Serious) Benzo Side Effects Respiratory Depression: Airway & Breathing (Oxygen already on) Upgrade to FM Stimulate patient/check resp rate Adjust upper airway (jaw thrust) Look for respiratory effort (?obstruction) Oral A/W, Jaw thrust Bag Mask Ventilation (100% O2) Antidote

Flumazenil Specific and exclusive benzodiazepine antagonist Dose dependent reversal of Sedation Respiratory Depression

Flumazenil Dosage: Duration of action Titration to desired level consciousness 0.1 mg IV q 1 min Typical dose 0.3 – 0.6mg to reverse side effects 0.5- 1 mg to abolish any benzo effect In overdose: 0.1 -0.4 mg/hr to maintain LOC Duration of action 30 to 60 min May require redosing

Flumazenil Side effects Nausea/Vomiting Possible seizures Chronic benzo user On anti-epileptic drugs

Local Anesthetics

Classification Amides Esters Lidocaine Bupivacaine Ropivacaine ... Chloroprocaine Procaine ...

Typical Use Infiltration ?Blocks

+/- Epinephrine Vasoconstrictor Decrease systemic absorption Decrease risk of toxicity Increase duration of block Greatest effect with lidocaine Less so with bupivacaine

+/- Epinephrine Contraindications: Anything that could fall off: Fingers/Toes Ears Nose Ankle  foot Male genitalia Unstable Cardiac condition CAD etc Arrhythmia

Infiltration Agent Lidocaine Bupivacaine Ropivacaine Max Dose+ 350/500* 175/225* 200 mg/kg 5/7* 2.5/3.2* 3 Duration (min) 30-120 120-240 60-360 * = with epinephrine + Assumes 70 kg patient

Systemic Toxicity Due to excess plasma concentration of any local anesthetic drug Different agents have different thresholds for major effects, but all can cause toxicity Main concerns Neurologic Cardiovascular

Neurologic Toxicity: Dose dependent effects (with increasing plasma concentrations): (Cardiovascular depression) Coma, Respiratory arrest Seizures, Unconsciousness Lightheadedness, Tinnitus, Numbness of tongue Analgesia

Cardiovascular Toxicity: Progression to (with increasing plasma concentrations): Sinus bradycardia, ventricular dysrhythmias, ARREST Decreased cardiac output, hypotension Hypertension, tachycardia

Toxicity Index Ratio of the dose required to produce each Cardiovascular Collapse : CNS toxicity Lidocaine: ~ 7 Bupivacaine: ~ 3.7

Avoiding LA Toxicity: Avoid: Good practice: Overdoses (absorption) Intravascular injection (short lived, high plasma concentration) Good practice: Give less than maximum dose Avoid intravascular injection Aspirate prior to injection Incremental dosing Use of epinephrine (where appropriate) Signs of intravascular injection (tachycardia, hypertension) Decrease rate of absorption

Treatment of LA Toxicity Avoidance Neurologic symptoms (i.e. Seizures) Supportive ABC’s Acidosis/hypoxia worsens effects of toxicity Oxygen +/- Ventilate +/- ETT Increase seizure threshold Midazolam Thankfully brief

Treatment of LA Toxicity Cardiovascular symptoms Supportive Call for HELP (CODE) ABC’s Control a/w Oxygen Ventilate +/- intubate Fluids Cardiopulmonary bypass (bupivacaine) Intralipid (bupivacaine) Lipid emulsion (similar to propofol carrier)