Factors that Increase MAC

HASHI needs more than 1 MAC

Hyperthermia

Alcohol abuse (chronic)

Sodium (hypernatremia)

Hyperbaric pressure

Increased central neurotransmitters

Factors that Decrease MAC

Less than 1 MAC makes you SHOP HAHA

Sodium (hyponatremia)

Hypothermia

Opioids

Pregnancy

Hypoxia

Alcohol (acute)

Hypovolemia

Age

Nitrous Oxide

Inhaled general anesthetic.  Inorganic gas that is less potent than other inhaled anesthetics (MAC = 104%).  Commonly used in combination with other agents because high solubility makes it very easy to control.

Causes direct myocardial depression, and is a mild sympatomimetic.  Increases CBF and ICP by vasodilation. 

AE include decreased methionine synthetase and granulocytopenia

Isoflurane

Inhaled general anesthetic that is a halogenated ether (decreases flammability).  MAC = 1.17%. Positive chronotrope and negative inotrope, that also causes vasodilation and increased HR.  Also acts as a bronchodilator.  Little effects on CBF. 

AE include cardiac ischemia due to positive chronotropy.  DOES NOT CAUSE ARRHYTHMIAS OR HEPATOTOXICITY COMPARED TO HALOTHANE

Desflurane

Inhaled general anesthetic that is a halogenated ether (reduces flammability).  MAC = 6.6%.  Causes significant SYMPATHETIC STIMULATION if [] increases too rapidly. 

AE include being extremely volatile and needing a special inhaler.  Also is very irritating.  Non-flammable and does not cause hepatotoxicity

Sevoflurane

Inhaled general anesthetic that is a halogenated ether (decreases flammability).  Similar to desflurane, but is MUCH LESS IRRITATING TO THE AIRWAY!!  Also acts as a bronchodilator and vasodilator and decreases HR.

AE include possibility of renal injury, but generally very safe.

Thiopental, Thiamylal, Methohexital

Mechanism of Action and Elimination

Barbituate IV general anesthetics with a binding site on the GABA_A receptor Cl^- channel.  This functions to decrease GABA dissociation from the receptor and, at higher concentrations, to activate the Cl channel autonomously.  Dosing based on BMI, age, and volume status

Rapidly mixes with the central blood pool and eliminated by redistribution.  With prolonged infusion, uptake by fat and clearance play increasing roles in the elimination

Barbituate Organ System Effects

CNS - Increased pain sensitivity in sub anesthetic [], decreased CBF, central O2 consumption, and ICP

CV - Venodilation (↓VR, ↓SV), ↓Contractility, Does not change SVR/MAP

Respiratory - Causes respiratory depression, and can lead to hypercarbia and hypoxemia

Barbituate Side Effects

When giving IV barbituates, you have to TAPE the syringe

Thrombosis/phlebitis

Anaphylaxis (non-IgE)

Porphyria (problems in heme synthesis)

Excitatory phenomena (rare)

Midazolam, Lorazepam, Diazepam

Mechanism and Pharmacokinetics

Benzodiazapenes that act on the GABA_A receptor to increase chloride conductance, but require the presence of GABA to function.  As receptor occupancy increases, anesthetic effects increases. Termination primarily via redistribution.  Must be used as adjuncts to other anesthetics

Duration of action:

Diazepam>Lorazepam>Midazolam

Benzodiazapene Organ

System Effects

CNS - Decreases cerebral O2 consumption, CBF, and induces ANTEROGRADE AMNESIA

CV - Minimal effects when used alone (additive effects with others), ↓BP with ↓SVR, does not block sympathetic response to noxious stimuli (get reflex tachy and HTN)

Respiratory - Central respiratory depression with increasing dose and apnea

Benzodiazapene Side Effects

Venous irritation at injection site

Prolonged post-operative sedation (REVERSED BY FLUMAZENIL)

Phencyclidines

Hallucinogenic IV general anesthetics that include LSD and PCP.  Ketamine is the only clinically used phencyclidine. 

Ketamine Organ System Effects

and Elimination

CNS - Dissociative anesthesia (eyes open, reflexes intact), muscle activity intact, ↑CBF, O2 use and ↑ICP.  Can induce seizures. Vivid dreams/agitation common in adult females

CV - Stimulates CV system (so useful in patients in shock), with increased HR, BP and CO.  ↑Myocardial O2 demand

Respiratory - Potent bronchodilator, so very useful in asthmatics, causes increased oral secretions

Elimination by hepatic metabolism and urinary excretion

Side Effects of Ketamine

-Increased myocardial O2 demand makes it difficult to use in patients with history of MI/angina/CAD

-Seizure risk

-Cannot be used in Schizophrenia

-↑ICP can cause herniations

Etomidate Organ System Effects

CNS - No analgesia, ↓CBF, CMRO2, and ICP, can induce seizures

Respiratory - Minimal effect on ventilation or bronchial sm m tone

CV - NO EFFECTS ON CV SYSTEM AT ALL, however, does not blunt sympathetic responses

Endocrine - Only one with endocrine, causes transient hypoadrenalism by inhibitng 11-β hydroxylase, resulting in decreased synthesis of cortisol and aldosterone

Etomidate Side Effects

and Elimination

AE include:

Nausea and vomiting very common (must give anti-emetics)

Pain on injection (must administer lidocaine first)

Myoclonus (uncoordinated muscle fasciculations)

Termination due to redistribution, while elimination is via hepatic metabolism and produces inactive metabolite

Propofol Elimination and Side Effects

Most popular and commonly used general IV anesthetic.

Termination by redistribution, while elimination is via hepatic conjugation to glucoronide and sulfate and renal excretion

AE include pain at injection site (must use lidocaine), myoclonus (less than etomidate), and contraindicated in hypovolemia

Propofol Organ System Effects

CNS - Acts at GABAA Cl channels, but has no analgesic properties; ↓ICP and perfusion due to ↓BP

Respiratory - Dose related respiratory suppression, with apnea common, though does cause bronchodilation

CV - Veno and vasodilator causing ↓preload and afterload, as well as ↓myocardial contractility.  Cannot use in trauma patients

General Use for Opioids

and Side Effect

Useful adjuvants to other anesthetics, that function to ↓MAC with inhaled anesthetics.  However, they do have a ceiling effect, and do not function as anesthetics themselves, because they have only analgesic properties (do not cause amnesia) so risk of recall exists.  Few CV effects and no organ toxicity

AE include non-specific CNS depression, some risk of anaphylaxis via histamine release, postoperative respiratory depression, and chest wall rigidity (especially with fentanyl)

Anesthetics for:

1) Routine Induction

2) Asthmatics

3) Hypovolemia

4) Myocardial Dysfunction

5) Continuous infusion

6) Porphyria

1) Routine Induction - Propofol, (thiopental)

2) Asthmatics - Bronchodilators Ketamine or Propofol

3) Hypovolemia - Ketamine, Etomidate, or Midazolam

4) Myocardial Dysfunction - Etomidate, Midazolam, or Fentanyl

5) Continuous Infusion - Propofol, ketamine (give lidocaine with both)

6) Porphyria - Propofol

Local Anesthetic Additives

(name 4 and benefits)

Epinephrine - Prolongation of block with local dosing, avoidance of cardiotoxic effects

Bicarbonate - LA are weak bases, so addition of HCO3 brings pH closer to pKa and makes more in unionized (active) form

Opioids - Can have additive analgesic effects with LAs, therefore allowing lower dosing of both agents, avoiding toxicity

Alpha 2 agonists (clonidine) - Act synergistically with LAs providing peripheral/neuraxial blocks.  No neurotoxicity.  Allow lower dosing

Lidocaine

(Local Anesthetic)

Most widely used amide local anesthetic for topical, nerve block or epidural.  Can be used for spinal block, but induces neurotoxicity at high doses.  Moderately rapid onset and duration; prolonged by addition of a vasoconstrictor (which also reduces toxicity). 

Specific toxicities associated with respiratory depression and cauda equina syndrome. 

Secondary use for ventricular arrhythmias

Bupivacaine and Levobupivacaine

(Local Anesthetic)

Longer duration amide local anesthetics that have greater sensory blockade than motor, making it ideal for epidurals during labor to allow movement with no sensation (walking anesthesia).  Also commonly used for spinal anesthesia.

Some risk of cardiotoxicity (torsades de pointes)

Ropivacaine

(Local Anesthetic)

Mepivacaine

Amide local anesthetic similar to lidocaine, with minimal vasodilation, so similar in effects to lidocaine + epinephrine.

Chloroprocaine

Ester local anesthetic with rapid onset and short duration of action, giving it a minimal toxicity profile due to rapid elimination.  High pKa makes it highly ionized, but low toxicity profile allows high (sufficient) doses to be given. 

Commonly used early until more long-lasting anesthetics "kick in"

Cocaine

(Local Anesthetic)

Opioid local anesthetic, unique in its vasocontrictor effects, and useful in anesthesia of nasal mucosa for intubation in the nose (prevents pain and bleeding).

Get similar effects with lidocaine + phenylephrine (α-1 agonist)

Non-anesthetic Properties of LAs

(Mechanism and specific situations)

Decrease release of inflammatory mediators

Prevent PMN chemotaxis and migration

Inhibit widening of endothelial gap junctions

Reduce superoxide radical formation

Commonly used in:  Acute lung injury, asthma, burns, MI, and sepsis

Also used in brain injury/ischemia and proves to salvage more neurons