Pharm E4- Surgery

What stage of anesthesia?

• Analgesia → pt experiences analgesia w/o amnesia

• towards the end, both analgesia and amnesia are produced

Stage I

What stage of anesthesia?

• Excitement

• pt is amnesic, often appears delirious and may vocalize

• irregular volume/rate of respiration

• retching & vomiting if pt stimulated (dangerous)

• try to avoid this stage → rapidly increase concentration of agent to limit duration & severity of this light stage of amnesia

Stage II

What stage of anesthesia?

• Surgical anesthesia

• recurrence of regular respiration

• extends to complete cessation of spontaneous respiration (apnea)

• 4 planes

Stage III

What stage of anesthesia?

• Medullary depression → deep stage

• severe CNS depression

  • vasomotor center in medulla, resp center in brain stem

• w/o circulatory & respiratory support → rapid death ensues

• *try to spend as little time here as possible

Stage IV

Inhaled anesthetics with a low blood:gas partition (doesn’t dissolve as much in blood) have a ______ onset than those with a higher blood solubility.

Faster

The concentration of an inhaled anesthetic in a mixture of gases (% of inspired air made up of drug) is proportional to _____

Partial pressure / tension

What is the MOA of inhaled anesthetics?

Activates GABA A receptor → chloride influx & hyper polarizes cells → unlikely for AP to occur

What is minimum alveolar anesthetic concentration (MAC)?

Median concentration to get a response rate in half of patients (immobility/not responding to painful stimuli)

*lower = more potent; higher = less potent

How much MAC is used to prevent movement in 95% of patients?

1.3x

What decreases MAC? (need less drug, brain more sensitive)

Elderly & hypothermia

What has no effect on MAC?

Sex, height, weight

What increases MAC? (need more drug, brain less sensitive)

Pregnancy, alcohol abuse, chronic use of centrally acting drugs

What is the order that inhaled anesthetic events occur, from first (lower MAC) to last (higher MAC)?

Amnesia < Unconsciousness < Immobility

What drugs are inhaled anesthetics?

Nitrous Oxide, Isoflurane, Sevoflurane, Desflurane, Enflurance, Halothane

Which inhaled anesthetic?

• potent; pleasant odor; eliminated in exhaled gas

• medium rate of onset & recovery (not ideal)

• lacks analgesic potency → need adjunct agents

• can cause arrhythmias

Halothane

Which inhaled anesthetic?

• less potent & more skeletal muscle relaxant than halothane

• medium rate of onset & recovery

  • but faster than halothane

Enflurane

What SEs are seen with Enflurane?

Resp depression, hypotension, hepatic & renal dysfunction, lower incidence of of arrhythmias than halothane

Which inhaled anesthetic?

• better muscle relaxant

• medium rate of onset & recovery

  • but faster than halothane & enflurane

• little post anesthetic organ toxicity / seizures & does NOT induce arrhythmias

Isoflurane

What SEs are seen with isoflurane?

Resp depression, hypotension, increased CO

Which inhaled anesthetic?

• low volatility (stays liquid at room temp, needs heated vaporizer)

• pungent

• poor induction (need adjunct IV agent)

• rapid recovery ~5 min

• used for outpatient surgery & emergencies

Desflurane

What are SEs of desflurane?

Myocardial depression, resp depression, coronary & cerebral artery dilation, laryngospasm

Which inhaled anesthetic?

• clear, colorless liquid

• rapid onset & recovery

• unstable in soda-lime

• pretreat with zofran to prevent N/V

Sevoflurane

What SEs are seen with sevoflurane (ultrane)?

N/V (pretreat w/ zofran), agitation, brady/tachyarrhythmia, hypotension

Which inhaled anesthetic?

• odorless, colorless gas at room temp/atmospheric pressure, excreted as gas

• incomplete anesthetic & not effective alone

  • not potent, high MAC

• rapid onset & recovery

• *pretreat w/ zofran to prevent N/V

Nitrous Oxide (N2O)

What are indications for for N2O?

Outpatient dental procedures & supplement to more potent anesthetics

What SEs are seen with N2O?

Hypotension, postoperative N/V (pretreat w/ zofran), expand volume of gas in air cavities → distention of bowel, rupture pulmonary cyst, rupture TM, PTX

What are CIs to nitrous oxide?

Pregnancy, immunosuppression, pernicious anemia

Which inhaled anesthetic?

• decreases MAP, CO, & HR

Halothane

Which inhaled anesthetic?

• decreases MAP & SVR

• increases HR

Desflurane & Isoflurane

Which inhaled anesthetic?

• decreases MAP & CO

Enflurane

Which inhaled anesthetic?

• decreases MAP & SVR

Sevoflurane

What condition?

• genetic disorder that occurs with general anesthesia d/t alteration in ryanodine receptor

  • dumps out all ca into cytoplasm → muscle contraction → burn through ATP & run out of O2 → lactic acidosis d/t switching from aerobic to aerobic metabolism

• most reliable dx test → caffeine halothane contracture test

Malignant hyperthermia

The following symptoms are seen in what condition?

• rapid onset tachycardia & HTN

• severe muscle rigidity

• hyperthermia, hyperkalemia

• lactic acidosis

• *after use of volatile inhaled anesthetics (not N2O)

Malignant hyperthermia

What is the treatment for malignant hyperthermia?

Dantrolene, reduce body temperature (cold IVFs, icepack, evaporative cooling), restore elytes & give bicarb if acidotic

What drug is a peripheral muscle relaxant that treats malignant hyperthermia by reducing calcium release from sarcoplasmic reticulum, allowing muscle to decouple & decrease acid/heat production?

Dantrolene

What agents provide additive sedation to IV anesthetics, with beneficial amnestic effects, quick offset & important to achieve balanced anesthesia?

Inhaled anesthetics

What are clinical uses for intravenous anesthetics?

Induction of general anesthesia, monotherapy, adjunct to inhaled anesthetics

*quick recovery time; most lack analgesia

What drugs are IV anesthetics?

Barbiturates, benzodiazepines, opioids, propofol, etomiidate, ketamine

What drugs are barbiturates?

Thiopental, phenobarbital, pentobarbital

What IV anesthetic?

• binds to GABA receptor & reversibly depresses activity of all excitable tissue in the CNS

• induction agent

• lacks analgesic properties

• decreases BP, CO, ICP → good for cerebral swelling d/ trauma

Barbiturates

What is the DOC in patients needing anesthesia for ECT?

Barbiturates

What IV anesthetic is good to use in patients with cerebral swelling because it does not increase ICP or BV?

Thiopental

What drug?

• anesthesia induction agent

• barbiturate that rapidly crosses BBB

• produces LOC for short amount off time

• potent respiratory depressant

• dose dependent decreases in BP, SV, CO

Thiopental

What must you do to the dose of thiopental if given with nitrous oxide?

Decrease

Which IV anesthetic?

• sedative, anxiolytic, & anterograde amnesia

• slower onset of CNS depressant effects

• rarely used as monotherapy, not an induction agent

• controls acute agitation → drug of choice for pre-medication

BZD

What drugs are benzodiazepines (BZD)?

Diazepam (muscle relaxing), Lorazepam (seizures), Midazolam (surgery)

What is the BZD of choice for parenteral administration, causes a high incidence of amnesia with a rapid onset, shorter elimination half life and a steeper dose response curve?

Midazolam

What is the antidote for when excessive BZD doses are administered that has a DOA (< 90 min) and helps prevent recurrence of CNS depressant effects (may need multiple doses)?

Flumazenil

Why should flumazenil be avoided in patients with chronic CNS depressant (BZD) dependence?

Can cause withdrawal seizures which can be deadly (tx w/ benzos)

What drugs are opioids?

Morphine, fentanyl, sufentanil, remifentanil, alfentanil

Which opioid, when given too quickly, can cause chest wall rigidity & impair ventilation?

Fentanyl

Which opioids are used in lower doses as adjuncts to IV and inhaled anesthetics for perioperative analgesia?

Fentanyl & sufentanil

Which opioids have a rapid onset of action and are used as co-induction agents with IV sedative-hypnotic anesthetics?

Remifentail (potent & short acting) & alfentanil

What is associated with high doses of potent opioids?

Awareness during anesthesia & postop recall (only analgesic properties), increased postop morbidity (prolonged vent support, GI & bladder comps)

How are opioids used for postop pain relief?

Very low doses via epidural & subarachnoid routes

What has a faster onset of anesthetic action, inhaled or intravenous?

Intravenous

What is the MOA of propofol?

GABA-A receptor agonist, increases cl influx

Which IV anesthetic?

• lipid emulsion

• rapidly metabolized & excreted in urine

• reduced postop N/V & pts are able to ambulate earlier

• induction & maintenance of anesthesia

Propofol

What are clinical uses for propofol?

IV sedation in OR, procedural sedation, prolonged sedation in ICU patients (may lead to delayed arousal)

*agent of choice for ambulatory surgery (like displaced fx)

What should be monitored for with propofol?

Hypertriglyceridemia (lipid base; high doses increase fat content in pts on TPN)

Severe acidosis w/ high dose & prolonged infusions

What drug can turn the urine green?

Propofol

What SEs are seen with propofol?

Transient apnea, pain at injection site, hypotension (if concerned, use versed + fent instead)

Which IV anesthetic?

• minimal CV/respiratory depression & hypotension

• no analgesic effects → need adjunct opioids

  • decreases cardiac responses & lessens spontaneous muscle movements

• hepatic metabolism

Etomidate

What are clinical uses for etomidate?

Induction of anesthesia in pts w/ limited CV reserve; rapid sequence intubation

What SEs are seen with etomidate?

Pain on injection, myoclonic activity, postop N/V (pretreat w/ zofran), adrenocortical suppression (give additional steroids)

What is the MOA of ketamine?

Blocks glutamic acid at NMDA receptor

What is the only IV anesthetic with both anesthetic & analgesic properties?

Ketamine

Which drug?

• Produces dissociative anesthetic state

  • unresponsive to stimuli, amnesia, analgesia, ±LOC

• inc cerebral BF, O2 consumption, & ICP

  • CI in head injury

• use in combo w/ other IV and inhaled anesthetics to minimize ventilatory depression

Ketamine

What is the sedative of choice in status asthmaticus?

*inc catecholamine / NE release → bronchodilators

Ketamine

What is there a high incidence of with ketamine?

Postop psychic phenomena → dysphoric, agitated, hallucinating (MC adults)

Which IV anesthetic?

• rapid onset & moderately fast recovery (< 10 min)

• provides CV stability

• decreased steroidogenesis & involuntary muscle movements

Etomidate

Which IV anesthetic?

• moderately rapid onset & recovery

• CV stimulation, increased cerebral blood flow

• emergence reactions impair recovery

Ketamine

Which IV anesthetic?

• slow onset & recovery

• used in balanced anesthesia and conscious sedation

• provides CV stability and marked amnesia

• reverse with flumazenil

Midazolam

Which IV anesthetic?

• rapid onset & recovery

• induction & maintenance

• can cause hypotension

• useful antiemetic action

• green pee!!

Propofol

Which IV anesthetic?

• rapid onset & rapid recovery w/ bolus dose

• slow recovery following infusion

• standard induction agent

• causes CV depression

• avoid in porphyrias

Thiopental

Which IV anesthetic?

• slow onset & recovery

• opioid used in balanced anesthesia & conscious sedation

• provides marked analgesia

• reverse w/ naloxone

• chest wall rigidity!!

Fentanyl

What is drug induced alleviation of anxiety & pain combined with altered consciousness w/ small doses of sedative medications in where a patent airway is maintained and pt is responsive to verbal commands?

Conscious sedation

Which medications that don’t have reversal agents can be used for conscious sedation?

*have short t½ so d/c and they’ll be fine

Propofol, ketamine

Which agents can be used for conscious sedation and have the advantage of being reversible?

BZDs & opioids

What combination of medications can be used for conscious sedation in the ICU?

Sedative hypnotics, low dose IV anesthetics, NMBs, dexmedetomidine

What drug?

• alpha 2 agonist → analgesic & mild sedative effects

• bolus followed by continuous infusion

• t ½ 2-3 hrs, hepatic metabolism, renal excretion

Dexmedetomidine

What sedative agent causes a light sedation and is therefore a good bridge for patients when you want to wake them up to extubate & discontinue opioids / versed?

Dexmedetomidine

What SE is seen with high doses of dexmedetomidine?

Hypotension & bradycardia

What is decreased consciousness where the patient is not easily aroused by painful stimuli (sternal rub), and is often accompanied by inability to maintain patent airway (ventilate) and lack of verbal responsiveness to stimuli?

*may be indistinguishable from IV anesthesia

Deep sedation

What medications are used for deep sedation?

Thiopental, midazolam, propofol, opioids, ketamine

What adjunct agents can be used to cause amnesia and prevent bradycardia & secretion of fluids into the respiratory tract?

Anticholinergics (ex- scopolamine)

What adjunct agents are good to control anxiety & facilitate amnesia?

BZDs

What adjunct agents are useful for sedation?

Barbiturates

Which antihistamine can be used as an adjunct agent to anesthesia to prevent allergic reactions?

Diphenhydramine

What antihistamine can be used as an adjunct agent to anesthesia to reduce gastric acidity?

Famotidine

What is the MOA of local anesthetics?

Bind & block voltage gated Na channels to inhibit APs → increased threshold for excitation → slows impulse conduction → decrease in rate & amplitude of AP → inability to generate AP with blockage of multiple na channels → pain signal never makes it to CNS

How does increased extracellular calcium affect the action of local anesthetics?

Antagonize

How does elevated extracellular potassium affect the action of local anesthetics?

Enhance

Why are vasoconstrictors added to local anesthetics?

Limits bleeding, reduces systemic absorption, higher local tissue concentration, lower systemic SEs, can give larger doses (good for larger areas needed to numb)

*less effective in more lipid soluble agents

Which local anesthetics are more water soluble, less lipid soluble (decreases DOA)?

*smaller → faster rate of interaction w/ Na channel receptor

Lidocaine, procaine, mepivacaine

Which local anesthetics are more lipophilic, more potent, & have a longer DOA?

Tetracaine, bupivacaine, ropivacaine, levobupivacaine

Which local anesthetics are short acting?

*better for ophtho procedures bc you dont want to inhibit blinking reflex for prolonged periods

Procaine & chloroprocaine

Which local anesthetics are intermediate acting?

Lidocaine, mepivacaine, prilocaine, articaine

Which local anesthetic has a fast onset & intermediate DOA and is ideal for dental procedures?

Articaine

What is an injectable combo preparation of lidocaine & bupivacaine to combine the quick onset & longer duration?

Duocaine