PT 14 Anesthetics General and Local

General Anesthesia

Puts patient into a reversible state of unconsciousness & with no recall of surgical events; usually administered for extensive surgical procedures

Laparotomy, thoracotomy, joint replacement, amputation

Adequate dosage

high enough to produce adequate level of anesthesia

Avoiding overdose

dosage must not be too high

Balancing effect

aim for high dosage with minimal side effects

Requirements of General Anesthesia

Rapid onset of anesthesia

Skeletal muscle relaxation

Inhibition of sensory and autonomic reflexes

Easy adjustment of anesthetic dosage during procedure

Minimum of toxic side effects

Rapid, uneventful recovery after administration is terminated

Amnesia

Stage I Induction stage

Analgesia

loss of somatic sensation but consciousness intact; some awareness of events

Patient is somewhat detached

Stage II Induction stage

Excitement (delirium)

unconscious and amnesiac but agitated & restless (thrashing); must move on quickly to stage III

Marked by increased HR and irregular breathing

Can progress to stage III by using both IV & inhaled anesthetic agent

Stage III Induction Stage

Surgical Anesthesia

desirable & begins with onset of regular, deep respiration; relaxed muscle tone

Target stage for surgery

Anesthetic should not be administered longer than necessary; might cause delay in recovery

Tapering off dosage towards end of procedure

Stage IV Medullary Paralysis

cessation of spontaneous respiration due to inhibition of respiratory control centers in medulla oblongata; respiratory & circulatory support must be provided

Spontaneous breathing stops; cardiovascular collapse & BP failure

Types of Inhaled Anesthetics (Volatile Liquids)

Desflurane(Suprane)

Enflurane(Ethrane)

Halothane(Fluothane)

Isofulrane(Forane)

Sevoflurane(Utane)

Types of Inhaled Anesthetics (gas)

Nitrous Oxide (Nitrogen monoxide)

Types of IV anesthetics (Barbiturates)

Methohexital(Brevital Sodium)

Thiopental (Pentothal)

Types of IV anesthetics (Benzodiazepines)

Diazepam (valium)

Lorazepam (Ativan)

Midazolam (Versed)

Types of IV anesthetics (Opioids)

Butorphanol (Stadol)

Fentanyl Derivatives(Sublimaze, others)

Meperidine (demerol)

Nalbuphine (Nubain)

Oxymorphone (Opana)

Pentazocine (Talwin)

Types of IV anesthetics(others)

Dexmedetomidine (Precedex)

Etomidate(Amidate)

Ketamine (Ketalar)

Fospropofol (Lusedra)

Propofol (Diprivan)

Balanced Anesthesia

usage of IV and inhaled agents in various combinations throughout surgery to provide optimal anesthetic effects with minimal side effects

Selection of General Anesthesia Depends on

Type & length of procedure

Surgeon's preference

Patient's decision

Coexisting diseases

Any possible drug interactions

Patient's position - affects anesthetic distribution

Advanced delivery systems of General anesthesia

Computerized feedback

Automated adjustments

Safety features with built-in alarms

Precision delivery

Inhaled Anesthetics

Long time for onset

Easier method of adjusting dosage during procedure

Exist either as gases or volatile liquids that can be easily mixed with air or oxygen then inhaled by a patient

Administered through endotracheal tube or a mask over the face

Ether

first anesthetic agent but replaced due to being volatile

Chloroform & cyclopropane were other earlier agents no longer in use due to being volatile/toxic

Halogenated volatile liquids

currently used, include enflurane, halothane, isoflurane, and the newer agents desflurane and sevoflurane

Desflurane & sevoflurane are often preferred because of rapid onset, faster recovery, and better control

Nitrous Oxide

only gaseous anesthetic widely used; reserved for short-term procedures such as tooth extractions

IV injected Anesthetics

Rapid onset, able to pass through first two stages quickly

Primary disadvantage is relative lack of control over level of anesthesia

CNS depressants can be injected intravenously to provide general anesthesia

Barbiturates

thiopental & methohexital have been used to induce anesthesia in many situations; fast onset & relatively safe but usage has recently declined in favor of newer drugs like propofol

Benzodiazepines and Opioid Analgesics

used to induce or help maintain general anesthesia; usually used as preoperative sedatives but larger doses can be used alone or in combination with other general anesthetics for short surgical or diagnostic procedures, or for when other agents are contraindicated

Ketamine

produces dissociative anesthesia wherein the patient appears detached or dissociated; awake but sedated & unable to recall events

May cause minimal respiratory depression

Psychotropic side effects (hallucinations, strange dreams, delusions etc.)

Takes a while to be eliminated from the body but does not cause respiratory or cardiac dysfunction

Useful for short diagnostic or surgical procedures and during invasive procedures in children & high-risk patients

Neuroleptanesthesia

combining opioid fentanyl with droperidol (antipsychotic) to produce a type of dissociative anesthesia; dissociation from environment with or without loss of consciousness

Used for short surgical procedures, including endoscopy or burn dressings or for patients who were seriously ill and might not tolerate general anesthesia using more conventional methods

No longer used routinely due to the development of safer regimens using fast-acting anesthetics or by combining opioids with propofol or midazolam (benzodiazepine)

Droperidol

currently used as antiemetic during and after surgery

Propofol

short-acting hypnotic that takes effect rapidly & is often drug of choice for general anesthesia; used for some short procedures or to maintain anesthesia in long procedures

Useful when early mobilization is desirable such as for THR/TKR patients who are at risk for embolism

Continuous Propofol Infusion

used to sedate critically ill ICU patients who are mechanically ventilated

Propofol Infusion Syndrome

rare but potentially fatal; bradycardia, metabolic acidosis, hyperlipidemia, rhabdomyolysis (destruction of muscle cells due to necrosis), and liver enlargement

Etomidate

hypnotic-like drug that causes a rapid onset of general anesthesia with a minimum of cardiopulmonary side effects; useful in patients with compromised cardiovascular or respiratory function

Fospropofol

converted to propofol in the body; used as an alternative to propofol during minor surgeries & diagnostic procedures

Dexmedetomidine

newer anesthetic used primarily for short-term (less than 24 hours) sedation in mechanically ventilated patients in the ICU

Can be used as adjunct during surgery to provide adequate anesthesia using relatively lower doses of the primary anesthetics

Differs chemically & functionally from more traditional anesthetics (stimulates alpha receptors in the brain)

Pharmacokinetics of General Anesthesia

Widely & uniformly distributed throughout the body

High degree of lipid solubility

May be temporarily stored in adipose tissue then slowly washed out during recovery

Confusion, disorientation, and lethargy may occurs as drug is redistributed to CNS

Dosages must be adjusted carefully depending on child's age and current level of function in the liver, kidneys, & other organs

Elimination occurs primarily through excretion from the lungs, biotransformation in the liver, or a combination of these two methods

If the person was anesthetized for an extended period of time and has large deposits of fat, this washout may take quite some time

Older People in General Anesthetics

need smaller concentrations of anesthetic, there is a greater chance that too much anesthetic will be administered during surgery

Mechanism of Action of General Anesthetics

Inhibit neuronal Activity thru out the CNS

In the Brain it decreases activity of neurons in the reticular system (RAS) resulting in Sedation, Hypnosis and Amnesia

In the Spinal Cord it produces Immobility and inhibits responses to stimuli

Unitary or General Perturbation Theory

Based on the premise that general anesthetic molecules dissolve directly in the nerve membrane's lipid bilayer

Once molecules are dissolved, they generally perturb membrane function by increasing its fluidity & disrupting the phospholipid bilayer

Decreased membrane excitability due to inability of ion channels to open & initiate action potential

Theory is based on the direct correlation between potency & lipid solubility; all general anesthetics produce the same effect despite different chemical structures

Specific Receptor Theory

Recent evidence suggest that general anesthetics bind to specific receptors located on the outer surface of CNS neurons (particularly GABAA)

GABA increases chloride influx which causes inhibition

Barbiturates, benzodiazepines, propofol, enflurane, halothane, and sevoflurane, increase the effects of GABA

Other agents may affect glycine receptors; increases chloride influx but to a greater extent and leads to increased inhibition

Halothane and Similar Inhaled Agents

may also activate specific pre- and postsynaptic potassium channels at excitatory synapses, thus increasing potassium exit from the cell and causing hyperpolarization and inhibition of these neurons

Also bind to ACh receptors on CNS neurons & inhibit their functions

N-Methyl-D-Aspartate (NMDA) Receptor

important site of action for certain agents, normally stimulated by excitatory amino acids like glutamate; blocked by ketamine & nitrous oxide

Opioids

decrease transmission in nociceptive pathways by binding to specific pre- and postsynaptic opioid receptors in the brain and spinal cord

Serotonin receptors and Neuronal Ion channels

other potential cellular targets but response is still debated

Dexmedetomidine (specific Receptor Theory)

Unique mechanism of action as an alpha-2 receptor agonist

Alpha 2 Receptors

located presynaptically in specific CNS pathways; activation of these receptors generally causes inhibition of neuronal activity in these pathways

Stimulation causes hypnosis via an effect in the locus coeruleus area of the brain

Preop medications that Decrease anxiety; facilitate induction of anesthesia

Amobarbital

Pentobarbital

Phenobarbital

Secobarbital

Preop medications that Decrease anxiety and tension; provide sedation and amnesia

Diazepam

Lorazepam

Midazolam

Pre op Medications that provide sedative hypnotic effects. Reduces Vomiting

Antihistamines:

Hydroxyzine

Promethazine

Prevent Salivation and respiratory tract secretions; reduce post op nausea and vomiting

Anticholinergics:

Atropine

Glycopyrrolate

Scopolamine

Reduce Gastric acidity; help prevent aspiration pneumonitis

H2 Receptor blockers antacids:

Cimetidine

Ranitidine

Reduce Post op Nausea and Vomiting

5-HT (serotonin) Receptor antagonist:

Granisetron

Ondasetron

Preop Medications

Given to patient 1-2 hours before administration of general anesthesia

Sedatives in Preop

usually administered orally or by IM injection; relaxes patient, reduces anxiety, and some may cause amnesiac effect

Commonly used are barbiturates, opioids, and benzodiazepines

Antihistamines in Pre op

dual advantage of producing sedation and reducing vomiting (antiemesis) during and after surgery

Histamine type 2 receptor blockers

drugs that decrease stomach acidity but can also reduce the risk of serious lung damage if gastric fluid is aspirated during general surgery

Dexamethasone

anti-inflammatory steroid that can help control post-op symptoms such as pain & vomiting

Ondansetron and granisetron

decrease postoperative nausea and vomiting via their ability to block certain CNS 5-HT3 (serotonin) receptors associated with GI function

Atropine and Scopolamine

anticholinergics that can help decrease post-op nausea & vomiting

Depolarizing Blocker

Succinylcholine

Nondepolarizing Blockers

Atracurium

Cisatracurium

Doxacurium

Gallamine

Metocurine

Mivacurium

Pancuronium

Pipecuronium

Rocuronium

Tubocurarine

Vecuronium

Succinylcholine

Anectine, Quelicin

Atracurium

Tracrium

Cisatracurium

Nimbex

Doxacurium

Nuromax

Gallamine

Flaxedil

Metocurine

Metubine

Mivacurium

Mivacron

Pancuronium

Pavulon

Rocuronium

Zemuron

Pipecuronium

Arduan

Tubocurarine

Tubarine

Vecuronium

Norcuron

Neuromuscular Blocker

Skeletal muscle paralysis is essential; patient must be relaxed to allow proper positioning and to prevent spontaneous contractions

Easier for patient to be mechanically ventilated due to thoracic wall being more compliant

Patient must be well into stage III and going into stage IV before muscle paralysis is complete

Drug that ensures skeletal muscle paralysis is given in conjunction with a general anesthetic to allow the use of a lower dose of anesthetic

Blocks postsynaptic ACh receptor at skeletal NMJ

Selection depends on desired length of action, side effects, patient factors, and reversibility

Possible side effects of NM blockers

Cardiovascular problems (tachycardia)

Increased histamine release - causes bronchoconstriction and consequently respiratory arrest

Hyperkalemia - increases plasma potassium levels that can lead to heart attack

Residual muscle pain & weakness

Immunological reactions (anaphylaxis)

Residual Paralysis

most serious complication in Nm blockers which skeletal muscle contraction remains depressed for several hours after the drug should have worn off

Neostigmine or edrophonium

inhibit acetylcholinesterase to prolong ACh effects and hasten motor function recovery

Sugammedex

rapidly inactivates two common neuromuscular blockers (rocuronium, vecuronium) by encapsulating them & terminating their ability to block the neuromuscular junction; works faster & has less side effects

Nondepolarizing Blockers

Pancuronium, vecuronium, and rocuronium

Competitive antagonists of the postsynaptic receptor

Prevents ACh from binding & results in paralysis of muscle cell

Depolarizing Blockers

Succinylcholine only agent in clinical use

acts like Ach by binding to and stimulating receptor to depolarize cell

Phase I - Prolonged Depolarization enzymatic degradation of drug is not as rapid as ACh degradation, so muscle cell is depolarized for a prolonged period; muscle is unresponsive to further stimulation

Phase II blockade - muscle cell eventually repolarizes but will remain unresponsive to stimulation by ACh due to receptor modification

Muscle tremor & fasciculation due to initial depolarization but followed by period of flaccid paralysis

Gradual return to neuromuscular function as drug is metabolized

Nerve stimulation, twitch response, and critical verification

Local Anesthesia

well-defined areas

Produces loss of sensation in specific body part or region

Involved introducing an anesthetic drug near the peripheral nerve that innervates the area to block neural transmission

Relatively rapid recovery & lack of residual effects

Does not interfered with cardiovascular, respiratory, or renal function

During childbirth, local (spinal) anesthesia imposes a lesser risk to the mother and neonate than general anesthesia

Primary disadvantage is length of time required to establish an anesthetic effect & the risk that analgesia will be incomplete/insufficient for the procedure

In nonsurgical situations, can be used to provide analgesia (either short-term or long-term pain relief)

May be used to block efferent sympathetic activity in conditions such as complex regional pain syndrome

PTs may administer local anesthetics via phonophoresis or iontophoresis if prescribed by a physician

Common Local Anesthetics

- Articaine

- Benzocaine

- Bupivacaine

- Butamben

- Chloroprocaine

- Dibucaine

- Levobupivacaine

- Lidocaine

- Mepivacaine

- Pramoxine

- Prilocaine

- Procaine

- Tetracaine

Atricaine

Onset of Action : Rapid

Duration: Intermediate

Principle use: Peripheral nerve block

Benzocaine

Principal use: Topical

Bupivacaine

Onset of action: slow to intermediate

Duration: Long

Principle use: Infiltration; peripheral nerve block; epidural; spinal; sympathetic block

Butamben

Principal use: topical

Choloroprocaine

Onset: Rapid

Duration: Short

Use: Infiltration; peripheral nerve block; epidural; IV regional block

Dibucaine

use: Topical

Etidocaine

Onset: rapid

Duration: long

Use: Infiltration; peripheral nerve block; epidural

Levobupivacaine

onset: Slow intermediate

duration: short to long

use: Infiltration; peripheral nerve block; epidural

Lidocaine

Onset: Rapid

Duration: Intermediate

Use: Infiltration; Peripheral Nerve block; Epidural; Spinal; Transdermal; Topical; Sympathetic Block; IV regional Block

Mepivacaine

Onset: Intermediate to rapid

Duration: Intermediate

Use: Infiltration; peripheral nerve block; Epidural; IV regional block

Pramoxine

Use: topical

Prilocaine

Onset: Rapid

Duration: Intermediate

Use: Infiltration; Peripheral Nerve block

Procaine

Onset: Intermediate

Duration: Short

Use: Infiltration Peripheral nerve block; spinal

Tetracaine

Onset: Rapid

Duration: intermediate to long

Use: topical; spinal

Common chemical structure of local anesthetic

lipophilic & hydrophilic groups connected by an intermediate chain

Selection of Local anesthetic is based on

Operative site & nature of procedure

Type of regional anesthesia desired

Patient's size & general health

Anesthetic's duration of action

Cocaine

first clinically used local anesthetic but no longer used due to abuse; high incidence of addiction & systemic toxicity

Pharmacokinetics of Local anesthetics

Administration varies depending on specific clinical situation; drug should remain at site of administration

Preventing the anesthetic from reaching the bloodstream is beneficial because local anesthetics can cause toxic side effects when sufficient amounts reach the systemic circulation.

Buildup in bloodstream should be monitored if larger doses are administered repeatedly/continuously to treat acute or chronic pain

Elimination occurs through metabolic hydrolysis in the liver & then excreted by kidneys

Procaine (pharmacokinetics)

injected into trigeminal nerve area during dental procedure; more effective if not washed away from administration site by blood flow through that region