Vicken Y. Totten MD, FACEP MS With help from Drs. David Cheng, Kelly Abbrescia, Tonya M. Thompson, and many others Sedation
Historical notes • Alcohol probably the earliest analgesic • Lousy analgesic, poor therapeutic window • Opiates x 1000s years • Highly valued, scarce • Chloroform / Ether / Nitrous Oxide • Major step towards anesthesia, analgesia
Objectives Review a few relevant definitions. Review goals of procedural sedation Review sedative agents
Definitions Pain: Noxious sensation transmitted by the nervous system to the brain; influenced by cognition and emotion. Sedation: a spectrum of reduced responsiveness to one’s environment Anesthesia: “no sensation” -- No response to environment, sometimes including own body needs Analgesia: “No pain” - relief of pain without anesthesia.
Dissociation (aka “dissociative sedation”). “The lights are on, and nobody’s home.” Disruption of perception with maintenance of neural activity Combines:i) sedation ii) analgesia iii) amnesia iv) maintenance of muscle tone More definitions
Anxiety: unpleasant emotional and physiological state of anticipating danger, pain, or distress. “Anxiolysis” – breaking anxiety. Reducing anxiety without producing sedation (ie. without reducing LOC) More definitions
Controlled sedation It’s a continuum! Reassurance general anesthesia. To the extent that you take control away from the patient, be prepared to substitute for those functions Sedation is NOT analgesia
Levels of sedation Minimal sedation / anxiolysis only no depression of consciousness Moderate sedation / moderately depressed LOC; still responds purposefully to verbal commands or light touch Deep sedation / markedly depressed LOC; responds purposefully only to intense or painful stimuli airway and respiratory function may be depressed
General anesthesia No purposeful response to any kind of stimuli. May have unconscious awareness of very painful stimuli (ie. HR RR BP ICP) airway and respiratory function profoundly depressed; typically require airway and ventilation assistance Autonomic & cardiovascular functions may be depressed We don’t want to go here.
Remember, it’s a… CONTINUUM
The Ideal ED Procedural Agent No anxiety before event. (Anxiolysis) No pain during event. (Analgesia) No memory of event. (Amnesia) And, complete function of all protective reflexes during the entire procedure
What Other Characteristics Would ED Procedural Agents Ideally Possess? Rapid onset Short duration of action. Rapid offset (ie. zero residual action). No hemodynamic effects. Easy to use and administer Wide therapeutic window Minimal contraindications Well tolerated (ie. minimal side-effects.)
Doesn’t exist. So we settle for… Analgesia: Local or General Sedation Anxiolysis, +/- amnesia for the event Protective reflexes usually diminished. How much diminution of reflexes is tolerable?
The moderately sedated state includes: marked anxiolysis full amnesia maintenance of airway, respiratory function, and cardiovascular function
Unfortunately, • Easy to overshoot from moderate sedation to deep sedation or to the anesthetic state. • loss of airway protection • marked respiratory depression • possible cardiovascular / autonomic depression. • Sedation not always analgesic
AMPLE Pre-Sedation Assessment- A-Allergies- Foods, medications, latex, act. M-Medications, including prior sedations and how tolerated. P-Past medical history L-Last PO intake E-Events leading to why patient is having sedation
ASA classes • ASA 1: Healthy • ASA 2: Mild controlled disease, 1 system; • ASA 3: Poorly controlled disease 1 major system • ASA 4:≥ 1 system; severe disease, constant threat to life • ASA 5: Moribund, imminent death, not expected to live
Get your team & Prepare • Additional person • “SOAP-ME”: • Suction • Oxygen • Airways (BVM, oral, LMA, ETT) • Pharmacy (meds) • Monitors • Equipment (defibrillator, airway supplies, etc)
Reversal Agents-don’t count on them • Naloxone • Competitively binds all 3 opiate receptors • IV, IM, SC, SL, ETT • 0.1 mg/kg • Flumazenil • Can terminate paradoxical reactions • 0.02 mg/kg • Lowers seizure threshold
Documentation & Monitoring • Time out • Record q5 minutes • SPO2 & ETCO2 / HR / BP / LOC • O2 given • Medications • Interventions
Remember for each drug… The agent’s specific procedural role Its onset / duration / offset Hemodynamic effects Contraindications Potential side-effects
Anxiolysis The standard: benzodiazepines Benzos (BZP’s) bind to and potentiate GABA (CNS inhibitory neurotransmitter) in smaller doses: 1) anxiolysis in larger doses: 1) sedation 2) amnesia 3) respiratory and CV depression
Midazolam (Versed) the standard Short acting, potent, reversible, safe. Hydroxylated by the liver. 1 active & 2 inactive metabolites. Metabolites are conjugated and excreted in the urine. Chronic alcoholics: potentiated metabolism,shortened duration of action Cirrhosis or renal failure: decreased metabolism,prolonged duration of action
Midazolam Highly lipid soluble at physiological pH rapid CNS uptake Peak effect within 1-5 minutes when given IV Duration of effect variable 30-60 minutes… Longer in the obese because of lipophilic distribution. Activity sub-therapeutic after 7-15 mins.
Midazolam, the good Has a wide therapeutic window. 1 mg -20 mg Reliably produces Anxiolysis Sedation Amnesia
Midazolam, the bad In large doses, or with sedatives such as alcohol, opioids, can produce… Profound sedation Respiratory depression Hypotension
Idiot’s Guide to Using Midazolam (Versed) Give initial dose & repeat q 3-5 minutes to desired effect Healthy adults: 1- 2 mg IV Drunk, high, elderly, cirrhotic, or RF pts: 0.5- 1 mg IV Chronic alcoholics — not currently drunk: 2 – 4 mg IV initially, then 1 – 2 mg IV prn
Side note: Remember, a variable amount of analgesic is going to be added. This may variably increase the level of sedation increase the potential for airway, respiratory, and cardiovascular compromise
Idiot’s Guide to Midazolam The role of midazolam is Anxiolysis Sedation & Amnesia NOT Analgesia Just because they aren’t kicking and screaming does not mean that they are pain free
Diprivan (Propofol) Highly-lipophilic Unique class of drug (structure is 1,6-diisopropylphenol) Multifaceted mechanism of action: GABA potentiation reduced excitability of sensory and motor neurons inhibition of the acetylcholine receptor channel
Diprivan (Propofol) Emulsified in Protein-free soybean oil with egg phosphatide Painful on intravenous injection (mechanism unclear) No preservatives — must be refrigerated, stored and handled properly in theory, most egg-allergic patients should tolerate this protein-free emulsion
Diprivan (Propofol) metabolism Liver inactive conjugates. Renal excretion Interestingly, chronic hepatic or renal failure has minimal effect on diprivan kinetics Propofol metabolism in the face of acute hepatic or renal failure has not been studied.
Diprivan (Propofol) the good anxiolytic/sedating effects Profoundly relaxing Amnestic properties Anticonvulsant properties Antiemetic properties Very short half-life
Diprivan (Propofol) the bad 3-5 minutes for effect (we’re impatient!) If dose overshoot Profound sedation / respiratory depression and/or apnea Frequent hypotension (pre-hydrate!) Worse with alcohol, opioids, or other sedatives; Caution: elderly or impaired hemodynamic status
Diprivan (Propofol) the Ugly Works better when injected slowly Need to give with lidocaine Has no analgesic properties Sedation potentiated by analgesia Amnesia somewhat inconsistent
Idiot’s Guide to Using Diprivan Infusion dosing: slower, but safer 0.3 mg / kg / min IV in adults (15 to 20 mg / min) 0.5 mg / kg / min IV in children Infuse at this rate until patient is adequately sedated, and then continue at this rate until the procedure is nearing completion
Idiot’s Guide to Using Propofol Bolus dosing: Faster. Greater risk of apnea, hypotension Bolus of 0.75 mg / kg IV in adults (40 to 65 mg) and 1 mg / kg IV in children If needed, give second ½ bolus in 2-3 mins Q 2-4 min, give 10-20 mg in adults (0.5 mg / kg in children) to maintain sedation.
Ketamine A derivative of PCP (animal tranquilizer / general anesthetic) Drug of abuse (“Special K”) Dissociative anesthetic Decouples incoming sensation from neurologic processing The patient has only internal or no stimuli to respond to.
Dissociation neural discontinuity between the cortico-thalamic system… responsible for higher-level functioning and the limbic system. responsible for emotions, motivations, and memory Return of coupling can be variable. This is turn is responsible for “emergence phenomena”
Dissociation effects include: Sedation Muscle tone and many reflexes maintained (eg. breathing, coughing, swallowing, corneal reflexes) Analgesia. Possibly greater analgesia for somatic (ie. body wall) pain as opposed to visceral (ie. organ) pain Amnesia
Ketamine metabolism P-450 cytochrome 3A4 to Norketamine Mildly active 20-30% activity. Does not cross Brain-Blood Barrier sufficiently to cause dissociation Metabolites conjugated and excreted in the urine Because the conjugated metabolites have so little activity, Ketamine’s duration of action is not greatly increased in renal failure.
Metabolic inducers Metabolism increased (duration reduced) with use of drugs that induce Cytochrome P-450 3A4: chronic alcohol consumption - chronic INH use - dexamethasone - rifampin - St. John’s Wort Anticonvulsants: Tegretol, Dilantin, Phenobarb
Metabolic inhibitors Metabolism decreased (duration prolonged) by acute alcohol consumption macrolides (ie. erythromycin, Biaxin, azithromycin) antifungals amiodarone cimetidine HIV protease inhibitors cyclosporine grapefruit juice
Ketamine Complex hemodynamic effects: Direct myocardial depressant and systemic vasodilator Indirectly stimulates the sympathetic system (possibly through inhibition of NE reuptake) Overall, typically: myocardial excitation O2 use, HR systemic vasoconstriction BP