Anesthesia Embodies control of three great concerns of humankind: Consciousness Pain Movement.
Pharmacokinetics What the body does to the drug –describes relationship bw DOSE and CONCENTRATION Involves: Absorption, Distribution, Elimination Route of Administration affects Absorption and therefore pharmacokinetics different rates of drug entry into the circulation based on admin route (IV, sublingual, IM, SubQ)
Distribution – delivery from the circulation to the tissues. Molecular size, capillary permeability, polarity, and lipid solubility, protein and tissue binding. The fluid volume in which a drug distributes is termed the volume of distribution (Vd).
Elimination – Varies widely Some drugs: Excreted unchanged Decomposed by plasma enzymes Degrated by liver
Take home Response to drugs varies widely Age Weight Sex Pregnancy, Disease state, Drug interactions Genetic factors
“The most important monitor in the operating room is the anesthesiologist, who continously assesses the patient’s response and adjusts the doses of anesthetic agents to match the surgical stimulus”
ABSITE Pearls Sublingual and rectal drugs do not pass through liver first So no “first pass effect” First-pass effect concentration of a drug is greatly reduced before it reaches the systemic circulation.concentrationdrug Zero order kinetics – constant amount of drug elimated regardless of dose 1 st order kinetics – constant amount of drug elimanted regardless of dose
Pharmacodynamics What the drug does to the body How plasma concentration of drug translates into effect on body Depends on biologic variability, receptor physiology, and clinical evaluations of the actual drug.
Vocabulary Agonist: causes a response. (full/partial) Antagonist: blocks an agonist Additive effect: effect is sum of parts Synergistic effect: effect greater than sum of parts Potency: dose required for effect. Efficacy: power to produce a desired effect. Dose-response curves compare dose and pharmacologic effect Effective dose (ED 50 ) desired effect in 50% of the gen pop. Lethal dose (LD 50 ) death in 50% of animals to which it is given. Ratio of the lethal dose and effective dose, LD 50 /ED 50, is the therapeutic index.
Local Anesthetics Local anesthetics block nerve conduction by stabilizing sodium channels in their closed state, preventing action potentials from propagating along the nerve.
Amides and Esters. Amides: Lidocaine, bupivacaine, ropivacaine have in common an amide all have ‘I’ in first part of name Lidocaine has a more rapid onset and is shorter acting than bupivacaine; however, both are widely used for tissue infiltration, regional nerve blocks, and spinal and epidural anesthesia.
Esters: Cocaine, tetracaine, and benzocaine have an ester linkage – Increased incidence of allergic reactions. Epinephrine is a vasoconstrictor, reduces local bleeding, and keeps local anesthetic in the nerve proximity for a longer period of time. Faster; Block Quality improved, longer duration Less local anesthetic absorbed in bloodstream – reducing toxicity Avoid epi in nose – toes – fingers - hose
Local Anesthetic Toxicity CNS – tinnitus, slurred speech, seizures, and unconsciousness CV - hypotension, increased P-R intervals, bradycardia, and cardiac arrest NEURO FIRST! Toxic dose Lidocaine 5 mg/kg Infected tissue hard to anesthetize 2 nd ary to acidosis.
Spinal Anesthesia Injected directly into the dural sac surrounding the spinal cord (subarachnoid space, where CSF lives) Possible complications include hypotension, especially if the patient is not adequately prehydrated High spinal block requires immediate airway management Spinal headache is related to the diameter and configuration of the spinal needle, and can be reduced to approximately 1%
Epidural Anesthesia Local anesthetics are injected into the epidural space surrounding the dural sac of the spinal cord Achieves analgesia from the sensory block, muscle relaxation from blockade of the motor nerves, and hypotension from blockade of the sympathetic nerves as they exit the spinal cord Provides only two of the three major components of anesthesia— analgesia and muscle relaxation Anxiolysis, amnesia, or sedation must be attained by supplemental IV administration of other drugs Complications are similar to those of spinal anesthesia
Epidural Bigger needle, accidental dural puncture often results in severe headache Blood patch in epidural space
General Anesthesia A triad of three major and separate effects: unconsciousness (and amnesia) analgesia muscle relaxation A combination of IV and inhaled drugs
Intravenous agents Produces unconsciousness and amnesia - frequently used for the induction of GA Barbiturates (sodium thopental), Benzodiazepines (versed), Propofol, Etomidate, Ketamine.
Barbiturates Fast acting Decreased cerebral blood flow and metabolic rate Hypotension
Propofol Very rapid on and off Amnesia and sedations NO ANALGESIA Profound hemodynamic effects – HYPOTENSION Respiratory Depression Decreased cerebral blood flow
Ketamine Dissociation (cataleptic state, amnesia and analgesia) NO RESPIRATORY DEPRESSION Hallucinations, increased secretions, increased cerebral blood flow CONTRAINDICATED IN HEAD INJURY Good for Kids
Etomidate Fewer hemodynamic changes, fast acting Continuous infusion can lead to adrenal insufficiency
Benzodiazepines Hepatically metabolized Anticonvulsant Amnestic Anxiolytic Respiratory depression NOT analgesic Flumazenil – competitive inhibitor may cause seizures and arrythmias, contraindicated in pts with elevated ICP or status epilepticus
Analgesia Narcotic – morphine (histamine release, constipation), demerol (seizures), codeine, fentanyl (80x stronger than morphine) Act on mu receptors Profound anagesia, respiratory depression, no cardiac effects, blunt sympathetic response Metabolized by liver, excreted by kidned NARCAN Non-narcotic Toradol Ketamine
Neuromuscular Blocking Agents Depolarizing – Succinylcholine – fast, short acting Rapid onset and offset Hyperkalemia ( not for burns, renal failure, SCI) Non-depolarizing – inhibit NMJ compete with ACH Pancuronium – long acting Rocuronium, vecuronium, – intermediate Reversed by neostigmine, edrophonium, Block ACETYLCHOLINESTERASE Increase ACH
Paralytics Diaphragm – last muscle to go down, first to recover Neck and face muscles – first to go down, last to recover
Inhalational Agents Provides all three characteristics of GA: unconsciousness, analgesia, and muscle relaxation A dose-dependent reduction in MAP (myocardial depression) Minimum alveolar concentration (MAC) - measure of anesthetic potency = smallest conc of agent at which 50% will not move w incision Small MAC MORE lipid soluble = MORE POTENT Speed of induction INVERSELY PROPORTIONAL to solubility Nitrous FAST but HIGH MAC = LOW POTENCY
Halothane – doesn’t smell bad, good for kids, HEPATITIS Enflurane - seizures
ASA Class I – healthy II – mild disease without limitation (controlled HTN, DM, obesity, older age) III – severe disease (angina, previous MI, moderate COPD) IV – severe constant threat to life (unstable angina, renal failure, severe COPD) V- moribund (rutured AAA, saddle PE)
Malignant Hyperthermia MH is a life-threatening, acute disorder, developing during or after general anesthesia Defect in calcium metabolism muscle excitation 1 st sign = incrase in end tidal CO2, fever, tachcardia, rigidity, acidosis, hyperkalemia, cardiac arrest, rise in temperature is often a late sign of MH genetic predisposition Triggering agents include all volatile anesthetics and the depolarizing muscle relaxant succinylcholine
Treatment must be aggressive and begin as soon as a case of MH is suspected Stop all volatile anesthetics and give 100% O 2 Hyperventilate the patient up to three times the calculated minute volume Begin infusion of dantrolene sodium 2.5mg/kg IV Repeat as necessary to titrate for clinical signs Continue dantrolene for atleast 24 hours Give bicarbonate to treat acidosis if dantrolene ineffective Treat hyperkalemia with insulin, glucose, and calcium Continue to monitor core temperature