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Induction Agents

Review of Induction Agents

TitleThiopentalMethohexitalPropofolEtomidateKetamineDexmedetomidine
Trade Name Pentothol, STP Brevital Diprivan Amidate Ketalar Precedex, DMD
Class Barbiturate: thiobarb Barbiturate: oxybarb Sedative/Hypnotic Hypnotic: imidazole ring Rapid Acting GA: phencyc. derivative Sedative/Hypnotic
IV Induction Dose Adult 4 mg/kg 1.5 mg/kg 2 mg/kg 0.3 mg/kg (pretreat w/ BZDPs or give slow to decrease myoclonus) NOTE: Don't decrease dose for elderly. This is the dose! 1.5 mg/kg IV 4-8 mg/kg IM 1 mcg/kg over 10 min
Available Conc. 25 mg/ml (2.5%) 10 mg/ml (1%) or 20 mg/ml (2%) 10 mg/ml (1%) std 20ml bottle - 2 hr limit 2 mg/ml (0.2%) 50 mg/ml (5%), 10mg/ml (1%) or 100 mg/ml (10%) 4 mcg/ml (200mcg/2ml in 48ml NS)
Acid or Base Acid Acid Acid Base Base Base
pKa (ionization) 7.6 (@7.4, > non-ionized) 7.9 (@7.4, > non-ionized) 11 (@7.4, >>> non-ionized) 4.2 (@7.4, >> non-ionized) 7.5 (@7.4, > ionized) 7.1 (@7.4, > non-ionized)
Solubility Lipid Lipid Lipid Water in acid; Lipid at phys. pH Lipid Lipid
Protein Binding 85% 85% **competes with coumadin binding site** 98% 75% 12% 94%
Sedative/ Hypnotic? Sedative Hypnotic Sedative Hypnotic Sedative Hypnotic Sedative Hypnotic Sedative NOT Hypnotic!! Sedative Hypnotic@ hi dose
Analgesia? In general, Barbs make pt more sensitive to pain, except in unconscious pt In general, Barbs make pt more sensitive to pain, except in unconscious pt NONE NONE Intense Analgesia with 0.2-0.5 mg/kg Intense Analgesia
Amnesia? NO NO YES!! (not Reliable) NO YES!! (until Redistribution) NO
Effect Site Equilibration (Onset) <30 sec <30 sec 15-45 sec 1 min IV: 1 min IM: 5 min 5-15 min
Duration 5-10 min (8.5) 5-10 min (5.6) 5-10 min 3-12 min 10-20 min (IM longer) 6 min
Action at Receptor Agonist @ GABA: Cl- influx, hyperpolarize Agonist @ GABA: Cl- influx, hyperpolarize Agonist @ GABA: Cl- influx, Due to less dissociation; hyperpolarize (also some inhibition at NMDA glutamate receptor) Agonist @ GABA Depress RAS Competitive antagonist of NMDA (glutamate); blocks opiod mu receptors; inhibits reuptake of NE -2 Agonist SC: inhibits Substance P, stim enkephalins & Ach
Ligand or second messenger? Ligand Ligand Ligand Ligand Ligand Second Messenger
CNS effects Dec CMRO2, ICP, CBF (Note: Barbs in general do not decrease CBF directly. It decreases by decreasing Metabolic requirements); protects from focal ishcemia; affects SSEP (But does not stop) Dec CMRO2, ICP, CBF( Note: Barbs in general do not decrease CBF directly. It decreases by decreasing Metabolic requirements); protects from focal ischemia Dec CMRO2, ICP, CBF (Auto Regulation intact); affects SSEP Dec CMRO2, ICP, CBF; Uncoupling of CBF and CMRO2 Inc CMRO2, ICP, CBF, dec cortical/thalamic function but stim Limbic system Dissociative Anesthesia Dec CMRO2, ICP, CBF; Uncoupling of CBF and CMRO2; inactivates locus cerelus; some muscle relaxation @ SC level
Burst Suppressive Yes Yes Yes (not DOC for this) Yes NO burst suppression NO burst suppression
Sz All Induction agents are anti siezure at high enough doses! Myoclonus, Epileptogenic at low doses. All Induction agents are anti siezure at high enough doses! All Induction agents are anti siezure at high enough doses! Myoclunus d/t muscle twitches NOT siezures; Can be used to map Sz. All Induction agents are anti siezure at high enough doses! Myoclonus. All Induction agents are anti siezure at high enough doses! All Induction agents are anti siezure at high enough doses!
CV effects Myocardial Depressant; Dec MAP ~20 mm Hg Myocardial Depressant; Dec MAP ~20 mm Hg Myocardial Depressant; Dec BP, SVR > Pentothol VERY STABLE Least Myocardial Depression; minimal decrease in SVR & BP Normally: increased SVR, PVR, HR, CO, BP, secondary to SNS stim from catecholamines. If you suppress catecholamines Ketamine becomes a PROFOUND Myocardial Depressant or in non-intact SNS. Does not release histamines. Does not trigger malignant hypothermia Decreased SNS response; transient HTN followed by decreased BP; vasodil (but constrict coronary arteries) GIVE SLOW, TAKE OFF SLOW!
Baro-receptor reflexes Blunted but Intact: Decreased BP & Increased HR d/t histamine release Intact: DecreasedBP & Increased HR Widens Range so NOT INTACT: no reflex tachycardia little change in HR or BP (blank) Enhances inhibitory effect of SNS: but may get exagerated response
Resp. Effects HISTAMINE RELEASE: Don't give to hyper-allergic pts. Dose dependent depression (strong); apnea with usual induction dose; bronchodilator; no blunting of laryngeal/tracheal reflexes Hiccuping at low doses. Dose dependent depression (strong); apnea with usual induction dose; bronchodilator; no blunting of laryngeal/tracheal reflexes Strongest Respiratory Depressant; surg stim can reverse depression; bronchodil, DOC in asthma; Apnea w/ induction; hypoxic pulmonary vasoctx is blunted but not stopped completely; premeds additive moderate respiratory depression < Barbs; apnea w/ induction dose esp with rapid administration Respiratory Sparing, Tracheo-laryngeal reflexes intact; Sialogogue (Give Robinul - quat., doesn't cross BBB, less tachy effect than atropine); Profound Bronchodilation Least Repiratory Depressant; Respiratory Sparing; Antisialogogue
Intubatable? Needs adjunct meds laryngeal reflexes intact Needs adjunct meds laryngeal reflexes intact YES!! Needs adjunct meds laryngeal reflexes intact Needs adjunct meds laryngeal reflexes intact Needs adjunct meds laryngeal reflexes intact
Metabolism/ Clearance SLOW. Dependent on blood flow to Liver. INTERMEDIATE. Dependent on blood flow to Liver. FAST. Dependent on blood flow to Liver. FAST. Dependent on blood flow to Liver. FAST. Dependent on blood flow to Liver. FAST. Dependent on blood flow to Liver.
E 1/2 life 11 hrs. 4 hrs. 0.5-1.5 hrs 2-5 hrs 2 hrs 1.5 hrs
Metabolites Active: Pentobarbital (in high doses only) (inactive) (inactive) (inactive) Active: Norketamine (30-50% as effective as Ketamine) (blank)
Enzyme Induction (ETOH is enzyme inducer!!) YES YES NO NO YES: Tolerant within 2 doses (esp burn patients!) (blank)
Liver/Kidney Disease Decreased protein binding and clearance Decreased protein binding and clearance Almost Unchanged Decreased protein binding and clearance Decreased protein binding and clearance Decreased protein binding and clearance
IV Sedation/ Infusion Not suitable for infusion except when isoelectric EEG needed; 15-40 mg/kg, then 0.5 mg/kg/min sedation: 0.5-1.5 mg/kg Not suitable for infusion; sedation: 0.2-0.4 mg/kg INFUSION OKAY; Sedation/MAC: 25-100 mcg/kg/min; GA/TIVA: 100-300 mcg/kg/min Very Titratable No Infusion: adrenocortical suppression Not suitable for infusion INFUSION OKAY; 0.2-0.7 mcg/kg/HR
Misc. Trivia Flush IV tubing well- precipitates; precipitates in artery*; Free Radical Scavenger; USE: approved for OB, long neuro cases to ICU, burst suppression painful injection, flush IV tubing well-precipitates; precipitates in artery*; off formulary in most countries USE: ECT and cardioversion with preop opioid/BZDP painful injection (use Lido), Antiemetic; propofol infusion syndrome; euphoria; gen.-contains sulfites; new h2o soluble-perineal burning; free radical scavenger; Ctxt Sens 1/2 time painful injection, PONV 30-60%, Adrenocortical suppression; dec dose in hypovolemia Delirium & Hallucinations on emergence: treat with BZDPs, propofol, barbs, opioids more natural, restorative sleep; anxiolysis, dec MAC 30-60% and opioid req, spinal mediated musc relax; dec hormonal/endocrine response to stress; treats postop shivering; reverse sedation with -1
Contras Acute Intermittent or Variegate Porphyria; Avoid Intra-arterial inj; Asthmatics; CHF; hypovolemia Acute Intermittent or Variegate Porphyria; Avoid Intra-arterial inj OB except asthmatics; children <17 yrs or ICU adults at high doses (>4mg/kg/hr) Acute Intermittent or Variegate Porphyria Neuro Trauma; CCA depletion (from other anesthetics, shock, hypovolemia, recreational drug users); Pts on MAOIs abrupt d/c (causes HTN)
Dose Adjust Increase Kids, Decrease elderly, ~30-40% Increase Kids, Decrease elderly, ~30-40% Increase Kids, Decrease elderly, ~30-40% Increase Kids, Decrease elderly, ~30-40% Increase Kids, Decrease elderly, ~30-40% Increase Kids, Decrease elderly, ~30-40%
Inhibits Hypoxic Pulm Vasocontriction No No Yes (blank) (blank) (blank)
Created by: jestevenson
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