A. Types of Anesthesia

1. General
2. Regional
3. Local

B. States of Sedation

1. Conscious Sedation
2. Sedation / Analgesia
3. Procedural Sedation
4. Deep Sedation
5. General Anesthesia

C. Properties

1. General Anesthesia
   1. State of sleep in which pain perception and its memory are ablated
   2. Analgesia, Amnesia, and Sedation
   3. Two General Types of Agents: Inhalation and Intravenous
   4. Induction and maintenance phases
   5. No prolongation of cognative dysfunction with general versus epidural in older adults [13]
2. Regional
   1. Nerve Block
   2. Epidural
   3. Spinal
3. Local
4. General and regional anesthesia can lead to hypothermia and complications [4]

D. Types of Nerve Fibers

1. Type A
   1. Alpha - motor, proprioception (6-14µm axon diameter)
   2. Beta - touch
   3. Gamma - muscle tone
   4. Delta - Pain, temperature, touch
2. Type B - autonomic
3. Type C - pain (0.5-1.5µm axon diameter)
4. Goal is generally blockade of Delta and Type C Fibers

1. Induction - usually with intravenous agent ± muscle relaxant (blocker)
2. Maintenance - inahation agent ± intravenous
3. Analgesia - usually opioid types, rapid acting; patient control (PCA) post-operative useful
4. Neuroleptic agents - alters state of consciousness, anti-nausea
5. Neuromuscular Blocking Agents - for induction, intubation, other uses

B. Intravenous Anesthetic Agents

1. Thiopental Sodium (Pentothal®)
   1. Ultrashort acting barbiturate
   2. Loss of consciousness within 30-60 seconds of iv administration
   3. Usually for procedures lasting <20 minutes
   4. Often with nitrous oxide, which reduces required doses by ~65%
   5. Very strong respiratory depressant; little to mild cardiovascular activity
   6. Contraindicated in porphyrias and cardiovascular dysfunction
2. Methohexital Sodium (Brevital®)
   1. Shorter duration than thiopental with more rapid hepatic clearance
   2. Does not induce release of histamine from mast cells
   3. Useful for very short procedures (eg. electoconvulsive therapy)
   4. Has analgesia activity
   5. Cardiovascular depressant - hypotension, anti-inotropic
3. Midazolam (Versed®)
   1. Water soluble benzodiazepine with short half life, rapid onset
   2. Induction occurs within about 80 seconds
   3. Respiratory depression may occur and patient should be monitored
   4. Slight cardiovascular decrease, but very mild
   5. Half life is ~1-2 hour
4. Diazepam (Valium®)
   1. Half life is age-dependent and can be >72 hours
   2. Onset of action is >60-120 seconds
   3. Good anti-convulsive activity
   4. Useful for moderate length local / regional procedures
5. Ketamine (Ketalar®)
   1. Non-barbiturate, given IV or IM
   2. Dissociated state of sedation and amnesia
   3. Single dose lasts ~10 minutes
   4. No cardiovascular depression; good in asthmatic patients
6. Propofol (Diprivan®)
   1. Induction or maintenance anesthesia, usually with opioids or inhalants
   2. Useful for <1-2 hour procedures not requiring analgesia
   3. Rapid induction time (within ~60 seconds)
   4. Rapid awakening when used alone
   5. Profound respiratory depression occurs, particularly with opioid drugs
   6. Cardiovascular lability can also occur, though infrequently

C. Rapid Acting Opioid Analgesics

1. Morphine
   1. Relatively weak agent with slow onset
   2. Elimination half-life 1.7-3.3 hours
   3. Causes histamine release, hypotension, reflexive sympathetic stimulation
   4. Little use in controlled anesthesia
2. Alfentanil
   1. About 10 fold more potent than morphine on a weight basis
   2. Very rapid onset of action
   3. Elimination half-life 1.4-1.5 hours
   4. Relatively wide disparity of responses between persons
3. Fentanyl (Sublimaze®)
   1. About 100 fold more potent than morphine
   2. Active half life may be shorter than elimination time due to rapid exit from CNS
   3. Elimination half-life 3.1-6.6 hours
   4. Preferred over morphine due to less hypotension, no histamine release
4. Remifentanil
   1. About 250 fold more potent than morphine
   2. Elimination half-life 0.17-0.33 hours
   3. This agent has the most rapid elimination due to hydrolysis by serum esterases
5. Sufentanil
   1. About 10 fold more potent than fentayl (1000X more than morphine)
   2. Usually more rapid anesthesia induction than fentanyl
   3. Little tendancy for accumulation, side effects
   4. Bradycardia is rare and responds to atropine
6. Narcotic Reversal
   1. Naloxone (Narcan®) - short acting and Nalmefene (Revex®) - long acting [8]
   2. Pure opiate receptor antagonists
   3. Acute, instantaneous reversal
   4. Short duration of action, usually shorter than opiate itself
   5. Need continuous IV naloxone or q30 second bolus injections
   6. Opiate blockade may cause acute hypertension

D. Droperidol (Inapsine®)

1. Butyrphenone (neuroleptic agent)
2. Produces an altered state of awareness, sedation, dysphoria
3. Little or no amnesia or analgesia
4. No respiratory effects, but some alpha-adrenergic blockade with transient hypotension
5. Anti-emetic actions
6. Frequently used in neurleptanesthesia and short procedures

E. Contraindications

1. Severe cardiorespiratory disease
2. Serotonin enhancing agents (mainly dietary aides) may cause autonomic dysfunction
3. Allergies to various agents

1. Suppress motor responses to noxious stimuli and produce amnesia
2. Affect both memory function and movement
   1. Spinal cord effects lead to reduction in movement on noxious stimuli
   2. Cerebral effecs lead to amnesia
3. Generally enhance gama-aminobutyric acid type A (GABA-A) receptors
4. Also likely inhibit nicotinic and glutamate receptors
5. Also bind to a variety of other proteins
   1. Other ligand-gated channels
   2. Various ion channels: potassium, sodium, calcium

B. Quantification of Pain Relief

1. MAC - Minimum Alveolar Concentration
   1. Inhaled anesthetic at 1 Atmosphere
   2. Results in immobility in 50% of patients subjected to surgical incision
2. Related to Oil/Gas partition coefficient
   1. Oil / Fat / Nerve
   2. MAC · Oil/Gas = 2.1

C. Factors which Influence MAC

1. Age - younger patients have higher MAC values
2. Temperature - hypothermia reduces MAC
3. Drugs - Narcotics and Diazepam decrease MAC

D. Halothane

1. Chemical Composition: CF3-CH(Cl)Br
2. Good anesthetic but mildly slow induction
   1. Most commonly used inhalation anesthetic in children in USA
   2. No longer used in adults due to halothane hepatitis
3. Decreases blood pressure and myocardial contractility, causes Tachycardia.
4. Excellent bronchodilator so used for asthma patients
5. Side Effects
   1. Tachycardia
   2. Shivering
   3. Halothane Hepatitis
   4. Induction of other ß-adrenergic mediated arrhythmias
   5. Malignant Hyperthermia (see below)
6. Halothane Hepatitis
   1. Autoimmune reaction against CuO-Halothane hepatotoxin
   2. More common in adults than children; common with repeated exposure
   3. Autoimmune response can evoke massive hepatitic necrosis and failure
   4. Rate of fulminant hepatitic failure is estimated at 1:30,000 patients exposed to agent
   5. All other agents have far lower risk of hepatitic failure, <1:800,000 or less

E. Fluranes [1,8]

1. Agents
   1. Enflurane
   2. Isoflurane (Forane®) - halogenated methy-ethyl ether, first generation
   3. Desflurane
   4. Sevoflurane
   5. These agents are potent, non-flammable and minimally metabolized
2. Enflurane
   1. Halogenated Methyl-Ethyl Ether
   2. Good muscle relaxant without hepatotoxicity
   3. May induce seizures
   4. Profound respiratory depression
3. Desflurane (Suprane®)
   1. Highly fluorinated, nearly insoluble, as potent as isoflurane
   2. Allows more rapid induction and emergence from anesthesia than isoflurane
   3. Desflurane can cause laryngospasm in children
   4. Desflurane can cause tachycardia and hypertension
4. Sevoflurane (Ultane®)
   1. Used in Japan for general anesthesia
   2. Highly fluorinated agent which causes high blood fluoride levels
   3. Pleasant odor which makes it a useful alternative to halothane in children
   4. Unstable in presence of calcium hydroxide, which absorbs CO2 during anesthesia
   5. Sevoflurane does not cause laryngospasm, and side effects are essentially zero
   6. No hepatitis or seizures, and cardiovascular system is stable on this agent

F. Nitrous Oxide

1. Nonexplosive, relatively weak agent
2. Reduces requirement for use of other inhalation (or intravenous) agents
3. Good analgesic properties; sedative for some types of regional anesthesia
4. Usually administered with neuromuscular blocking agent if muscle relaxation required
5. Sedation typically at 25% nitrous oxide; anesthesia at 25-50%

1. Pain is perceived as stimulus but is not viewed as noxious
2. Dissociation between stimulus and effects
3. Includes spinal (regiona) anesthetics
4. Ketamine is usually used (see above)

B. Effects

1. Hallucinogenic - mainly occurs in adults (ie. not children)
2. Increased Respiratory Rate
3. Short Acting

C. Utilization

1. Cardiac and Respiratory Reflexes intact
2. Blood pressure is maintained
3. Short duration of action allows for close control

D. Adverse Effects

1. Hallucinogenic
2. Increased intracranial and intraocular pressures
3. Possible long term psychological disturbances

1. Sedative / Neuroleptic
   1. Droperidol is very common (see above)
   2. Benzodiazepine - typically diazepam, lorazepam, or midazolam
   3. Decreased anxiety, usually in semi-conscious patient
2. Narcotic - decreased sensation (pain), motor activity
3. See discussion of agents above

B. Properties

1. Decreased motor activity and anxiety
2. Produces indifference to pain
3. Patients will follow commands
4. Adrenolytic, antiemetic, anti-fibrillatory

C. Complications

1. Muscle rigidity - difficulty breathing
2. Respiratory depression - narcotic effect
3. Extrapyramidal effects - strange movements
4. Bronchoconstriction

1. Depolarizing - succinylcholine is the only approved agent in this class
2. Nondepolarizing - competitive inhibition of ACh binding
3. Definitions
   1. Acetylcholine (ACh) is the neuromuscular junction hormone
   2. Binding of ACh to its receptor leads to depolarization of the nerve
   3. Depolarization occurs due to sodium and calcium entry through membrane chanel
   4. Depolarizing agents mimic ACh by binding to alpha subunit and opening chanels
   5. Nondepolarizing agents bind alpha subunits and prevent chanel opening

B. Succinylcholine (Suxamethonium®)

1. Onset within 1 minute with 7-8 minute duration of blockade
2. Useful for rapid tracheal intubation
   1. Prevents aspiration of gastric contents
   2. Therefore, its use is usually restricted to an intubation where aspiration is a concern
   3. Rocuronium has rapid onset of action and may suppress aspiration also
3. Side Effects
   1. Postoperative muscle pain
   2. Hyperkalemia
   3. Increased intraocular and intragastric pressure
   4. Malignant Hyperthermia (rare, but potentially fatal)
   5. Vagal stimulation
   6. Use with halothane may precipitate myopathic crisis
4. Malignant Hyperthermia [9,10]
   1. Occurs in about 1 case per 50,000 adults, 1 in 15,000 children (usually familial)
   2. With careful observation and supportive therapy, mortality is now <10%
   3. Mutations in the sarcolemmal calcium release channel (CRC), also called the ryanodine receptor, are responsible malignant hyperthermia (MH)
   4. At least 16 different mutations in skeletal CRC gene Ryr1 linked to MH
   5. CRC controls muscle calcium (Ca2+) flux
   6. Anesthetics inducing MH cause massive unregulated Ca2+ release
   7. Increased uptake of Ca2+ by mitochondria leads to increased CO2 production, O2 use
   8. Muscle rigidity, hyperthermia, hypercapnea, hyperkalemia, and arrhythmias occur
   9. Acidosis, rhabdomyolysis with myoglobinemia, renal failure, DIC can occur
   10. Dantrolene, which closes CRC, is major treatment modality for MH

C. Non-Depolarizing Agents

1. Quarternary ammonium compounds, bind to alpha subunit of ACh Receptor
2. Slower onset of action compared with succinylcholine
3. Longer duration of action, and fewer side effects compared with succinylcholine
4. Examples
   1. Mivacurium - short acting; may cause histamine release
   2. Vecuronium - intermediate acting (onset ~5 minutes, duration 20-25 minutes)
   3. Atracurium - intermediate acting; may cause histamine release
   4. Cisatracurium - intermediate acting; minimal histamine release
   5. Rocuronium - intermediate acting with 2-3 minute onset; no histamine release
   6. Pipecuronium - long acting (4-6 minute onset; 60-100 minute duration)
   7. Doxacurium - delayed onset (10-14 minutes) with long acting duration
   8. Pancuronium (Pavulon®) - long acting; also causes tachycardia
5. Side Effects
   1. Cardiovascular - mainly with older drugs, include hypertension and tachycardia
   2. Histamine release - tubocurarine, mivacurium
   3. Critical illness myopathy (may include calcifications, "myositis ossificans")
6. Atracurium or vecuronium (cisatracurium and rocuronium) are agents of choice

D. Indications For Use [6]

1. Endotracheal Intubation
2. Endoscopy
3. Decreased Lung (or chest wall) Compliance - eg. ARDS
4. Elevated intracranial pressure
5. Inappropriate or unsuppressible respirations
6. Tetnus
7. Status asthmaticus / Status Epilepticus
8. Reduce work of breathing
9. Surgical Procedures
10. Others

1. Calcium on nerve membranes replaced by local anesthetic
2. Decreased Na+ permeability
3. Decreased rate of depolarization
4. Failure to Propagate Action Potential
5. Requires basic pH for good lipid penetration (protonated at low pH)

B. Types of Agents

1. Esters
   1. Metabolized by pseudocholinesterase in blood
   2. Cocaine - vasoconstriction as well as numbing (sympathomimetic activity)
   3. Procaine (Novocain®) - short acting (15-90 minutes)
   4. Chloroprocaine (Nesacine®)
   5. Tetracaine (Pontocaine®) - spinal
2. Amides [5,14]
   1. Metabolized by liver
   2. Lidocaine (Xylocaine®) - 1-2 hour duration, 0.5-2% solutions
   3. Prilocaine (Citanest®) - dental anesthetic only (in USA)
   4. Bupivacaine (Marcaine®, Sensorcaine®) - long acting 4-16 hr, 0.125-0.25% solutions
   5. Ropivacaine (Naropin®) - slightly less potent than bupivacaine, less cardiotoxic
   6. Mepivacaine (Carbocaine®)
3. Allergies to Agents [7]
   1. Usually due to presence of preservatives such as methylparaben
   2. Cardiac grade lidocaine does not contain preservatives
   3. Allergies to one class of agents (eg. esters) rarely cross to other class (eg. amides)
4. Lidocaine may be quite toxic in setting of liposuction [11]
   1. Hypotension, bradycardia, and subsequent cardiac arrest have occurred
   2. Hepatic metabolism of lidocaine is saturable, and serum levels may rise quickly
   3. General anesthesia or anesthesia with conscious sedation can mask signs of early lidocaine toxicity
5. Clonidine can enhance the effects of epidural local anesthetics [14]

C. Sites of Application

1. Infiltration (local)
   1. Extravascular with caution due to intravascular administration
   2. Often used with epinephrine to reduce bleeding and intravascular uptake
2. Peripheral Nerve Block (Field Block)
3. Central Neural Block
   1. Epidural
   2. Spinal (intrathecal and subarachnoid)
   3. Topical
4. Epidural anesthesia is generally superior to parenteral opioids for post-operative pain [16]

D. Epinephrine

1. Epinephrine (1:100,000) included with anesthetic
2. Decreases venous uptake of anesthetic and increases duration of activity
3. Also causes vasoconstriction with blanching in area of infusion
4. Not recommended in distal areas of body (eg. fingertips) due to vasoconstrictor activity

E. Utility

1. Used alone for smaller proceedures - often for lacerations
2. Local anesthetic with intravenous sedation (usually benzodiazepine) for longer proceedures
3. Regional blockade as above

F. Toxicity

1. Lidocaine - Seizures (CNS effects)
2. Prilocaine - Methemoglobinemia
3. Bupivacaine - cardiovascular collapse (not likely with current dosage regimen)
4. Epinephrine can cause necrosis in local area if too much is used
5. Local skin infections, indwelling cathter problems, mental status changes

1. Mainly in children; overall ~20% of cases
2. Severe emesis very uncommon (0.15%)
3. Higher with fentanyl, lower with propofol
4. Controlled well with standard agents
   1. Serotonergic receptor type 3 antagonists are the most effective
   2. Ondansetron (Zofran®), granisetron (Kytril®), dolasetron and others
   3. Older agents including droperidol and metoclopramide are less effective

B. Aspiration Pnemonitis and Pneumonia

1. Aspiration of gastric contents occurs in about 1 in every 3000 operations
2. May be related to "emergency" surgery when patient has recently eaten
3. Overall mortality was less than 1 in 70,000 cases
4. Aspiration pneumonia may develop, particularly in ventilated patients

C. Renal Failure

1. Many anesthetic agents cause hypotension (see below)
2. Renal medulla is highly sensitive to hypoperfusion
3. In addition, anesthetics induce anti-diuretic hormone
4. Acute tubular necrosis (ATN) is very uncommon in absence of predisposing conditions
   1. Pre-existing renal disease
   2. Surgery associated with heavy blood loss or emergency situation
   3. Myoglobulinuria due to rhabdomyolysis
   4. Administration of radiocontrast dye
5. Sevoflurane metabolism may also produce nephrotoxic levels of fluoride

D. Hepatic Dysfunction

1. Cytochromie P450 mediated production of reactive metabolites
   1. Halothane
   2. Methoxyflurane
   3. Extremely rare with enflurane isoflurane
2. Liver hypoperfusion due to hypotension also plays a role
   1. Inhaled agents
   2. Sympathetic blockade
   3. Use of vasoconstrictors
   4. Opioides
   5. Surgical manipulation
3. Supportive care usually sufficient to allow liver to recover function

Resources

Mean Arterial Pressure (MAP)

References

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