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Induction Agents
Review of Induction Agents
Title | Thiopental | Methohexital | Propofol | Etomidate | Ketamine | Dexmedetomidine |
---|---|---|---|---|---|---|
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) |