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LECTURE NOTES – GENERAL ANESTHESIA (DR.

CORPORAL) 1
GENERAL ANESTHESIA - Use Neuromuscular blocking agents
- If you are uncomfortable in intubating, the more there will be o muscle relaxation, ↓ risk of aspiration
edema unless patient is cyanotic - GCS 7-8: indication for intubation → protect the airway in case
o Do ventilation instead there will be vomiting (protective)
- Contraindication for ventilation: Full stomach (has eaten 6hrs - Alternatives: facemask; Laryngeal mask
before event)
o May vomit → regurgitate → aspiration pneumonia C. HYPOTHERMIA – body temp < 36
1. Lower core temp set point → thermoregulatory
5 components: vasoconstriction activated to defend against heat loss
1. Amnesia 2. Vasodilation redistributes heat from central to peripheral
2. Analgesia body compartments – decline in core temperature
3. Unconsciousness 3. Metabolic rate and total body oxygen consumption
4. Immobility in response to noxious stimulation o ↓ by 30% = ↓ heat generation
5. Attenuation of autonomic responses to noxious stimulation *Modalities to maintain normothermia
- Using warm IV fluids
Methods: - Heat exchangers in the anesthesia circuit
1. Inhalational Anesthesia - Forced-warm-air covers
2. Total IV Anesthesia (TIVA) – via dextrose - Water-filled garments with microprocessor feedback control to a
3. Mixed Inhalation and IV Anesthesia core temperature set point

Objectives: D. NAUSEA AND VOMITING


1. Minimizing deleterious direct and indirect effects of anesthetic 1. Caused by an action of anesthetics on the chemoreceptor
agents and techniques trigger zone and the brainstem vomiting centre
o Cardiodepressants- most o Modulated by: Serotonin (5-HT), Histamine, Ach, DA, and
2. Sustaining physiologic homeostasis during surgical procedures Neurokinin (NK1)
o Major blood loss *Modalities for tx
o Tissue ischemia - 5HT3-receptor antagonists: Ondasetron, Dolasetron
o Fluid shifts - Metoclopramide, Dexamethasone, Droperidol
o Exposure to a cold environment - Avoidance of N2O
o Impaired coagulation - Use of Propofol
o Reperfusion of ischemic tissue - Use of NSAIDs instead of opioids
3. Improving postoperative outcomes o Tramadol, fentanyl, morphine (opioid)
o blocks surgical stress response o Mefenamic acid (NSAIDs)
Tourniquet – controls bleeding o Coxibs – Celecoxib, Eterecoxib (selective COX-2 inhibitor)
- Careful of reperfusion injury when removing tourniquet - NK1 antagonist: Aprepitant, Rolapitant
Electrolytes may cause tachycardia
- Should know how to manage patients EMERGENCE AND POSTOP PHENOMENA
Michael Jackson – died because of Propofol 1. Hypertension and tachycardia– SNS regains tone, pain
2. Emergence excitement (5-30%) – tachycardia, restlessness,
EFFECTS OF ANESTHESIA crying, moaning, and thrashing
A. HEMODYNAMIC EFFECTS 3. Neurologic signs – delirium, spasticity, hyperreflexia, Babinski sign
- ↓ Systemic blood pressure 4. Postanesthesia shivering – core hypothermia
o Direct vasodilation and myocardial depression o tx: Meperidine
o Blunting of baroreceptor control o Give Demerol for shivering
o Generalized decrease in central sympathetic tone 5. Airway obstruction – residual anesthetic effects
o Enhanced by underlying volume depletion or preexisting 6. Negative-pressure pulmonary edema – strong inspiratory efforts
myocardial dysfunction against a closed glottis
Clinical case: In trauma cases o Laryngospasm – cannot exhale or inhale (during extubation)
→ Give non-sugar, and non-D5 containing solution → stress increases → triggered by secretions or with light anesthesia during
catecholamines → hyperglycemia (do not worsen) deep intubation
- Crystalloids – 1:3 (500ml blood loss:1500ml) 7. Reduced pulmonary function, hypoxemia
- Colloids – 1:1 (500ml blood loss:500ml) 8. Pain
- Blood products – 1:1
POTENCY: measured by determining conc’n of general anesthetic that
B. RESPIRATORY EFFECTS prevents movement in response to surgical stimulation
1. Reduction/elimination of ventilatory drive and reflexes that MAC: minimum alveolar conc’n that prevents movement in response
maintain airway patency to surgical stimulation in 50% of subjects
2. Gag reflex is lost MACawake: minimum alveolar conc’n at which 50% of subjects
o Give Succinylcholine – used for intubation (w/in 1 minute appropriately respond to verbal commands
patient is paralyzed)
3. Stimulus to cough is blunted
4. Lower esophageal sphincter tone is reduced - both passive and
active regurgitation may occur
- Endotracheal intubation: introduced by Kuhn in the early 1900s →
Decline in number of aspiration deaths during GA
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LECTURE NOTES – GENERAL ANESTHESIA (DR. CORPORAL) 2
12th edition TABLE

- Anesthetic conc’n required to produce amnesia and immobility NMDA receptors


vary significantly among different inhalational anesthetic agents - KETAMINE – dissociative anesthesia
suggesting different cellular and molecular mechanisms for o Patients are unconscious but eyes are open
different endpoints o Hallucination, vivid dreams
MECHANISM OF ANESTHESIA o Inhibits NMDA receptor by binding to phencyclidine site
*Unitary Theory of Anesthesia o NMDA antagonist
- Anesthesia is produced by perturbation of physical properties of o No effect on GABAa and glycine receptors
cell membrane - Nitrous Oxide
*Meyer-Overton Rule - Cyclopropane
- The greater is the lipid solubility of the compound in olive oil the - Xenon
greater is the anesthetic potency o Inhibits NMDA-activated currents
- Lipid bilayer: target of action
- Has largely been discarded Two-pore K channel
- This realization has focused thinking on identification of specific - Located in both pre-synaptic and post-synaptic sites
protein binding sites for anesthetics - Activation leads to hyperpolarization – reducing NT release
- Inhalational anesthetics, Xenon, Nitrous oxide, Cyclopropane
*Molecular Actions of General Anesthetics o Activate some members of a class of K channels
- GABAa receptors
- Glycine receptors Cellular mechanisms of Anesthesia
- Nicotinic ACh receptors 1. Hyperpolarization of neurons
- NMDA receptor 2. Substantial effects on synaptic transmission & smaller effect
- Two-pore K channel on action potential generation propagation

GABA receptors- inhibitory PARENTERAL ANESTHETICS


Cl channels gated by inhibitory GABAa receptors → General - Hydrophobicity – key factor governing pharmacokinetics
anesthetics ↑ sensitivity of GABAa receptor to GABA → enhance - IV bolus – go to highly perfused and lipophilic tissues of the brain
inhibitory neurotransmission & depressing NS activity and spinal cord → produce anesthesia
- If GABA is stimulated → Cl channels open → hyperpolarizes the - Blood levels fall rapidly – drug redistribution out of the CNS back
cell into the blood
- Hyperpolarization → downer - Anesthetic diffuses into muscle and viscera (less perfused area) –
adipose tissue (poorly perfused area)
PROPOFOL, ETOMIDATE
B3 subunit of GABAa receptor inhibit response to noxious stimuli CONTEXT SENSITIVE HALF TIME
B2 subunit of GABAa receptor sedative effect - Time required for blood or plasma concentrations of a drug to
decrease by 50% after discontinuation of drug administration
GLYCINE receptors – inhibitory - Cannot be predicted by the elimination half-life – because it also
NICOTINIC ACh receptors – only found in skeletal muscles → depends on drug distribution
diaphragm can be affected - Helps explain the duration of action of a drug given by infusion
- NMDA = Glycine + Glutamine must attach before it is activated after stopping the infusion

Inhalational anesthetic PROPOFOL, FOSPROPOFOL


- enhance the capacity of glycine to activate glycine-gated chloride - 1% (10mg/ml) emulsion in 10% soybean oil, 2.25% glycerol, 1.2%
channels – inhibitory neurotransmission in the spinal cord and purified egg
brainstem - Significant pain on injection; short duration of action
o Also causes opening of Cl channels - Good for ambulatory surgery
- Inhibit some classes of neuronal nicotinic ACh receptors – mediate - GABAa agonist → ↑ Cl conduction → Hyperpolarization →
analgesia and amnesia sedation & hypnosis
- Less likely to provoke bronchospasm – induction agent of choice in
ASTHMATICS
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LECTURE NOTES – GENERAL ANESTHESIA (DR. CORPORAL) 3
S/E - inadvertent intra-arterial injection of thiobarbiturates can induce a
- ↓CBF, ICP, IOP severe inflammatory and potentially necrotic reaction that can
- ↓ BP (dose dependent) threaten limb survival
o due to vasodilation & depression of myocardial contractility - DO NOT TRIGGER MALIGNANT HYPERTHERMIA
- NO ANALGESIC EFFECT – add opioid usually fentanyl
- Anti-emetic action INHALATIONAL ANESTHETICS
- Safe for use in pregnant women - Administered as gas
o Transient depression in the newborn - Troublesome property: low safety margin
- DOES NOT TRIGGER MALIGNANT HYPERTHERMIA - Most dangerous drugs in clinical use: Therapeutic index
*Propofol Infusion Syndrome (LD50/ED50) from 2-4
o Prolonged, higher-dose infusions in young or head-injured px - Toxicity = side effects – selection based on matching a patient’s
o Metabolic acidosis, hyperlipidemia, rhabdomyolysis, enlarged pathophysiology with drug side effect profiles
liver Uptake of Inhalational Anesthetics
▪ Alteration in mitochondrial metabolism and electron
transport chain function

ETOMIDATE
- GABAa receptor agonist
- Primary indication: anesthetic induction of patients at risk for
HYPOTENSION
o Propofol cannot be given to hypotensive px → bradycardia, ↓
BP
- Maintains CV stability in px with coronary artery dse,
cardiomyopathy, cerebral vascular disease or hypovolemia
- Pain on injection – reduced by lidocaine
- Induce hiccups
- No histamine release
- 2 major drawbacks
o Nausea and vomiting
o Inhibits adrenal biosynthetic enzymes required for the
production of cortisol and some other steroids
- Shows uptake of inhalational anesthetics
KETAMINE - Less solubility = faster equilibrium of alveolar and inspired
- NMDA ANTAGONIST anesthetic
- For patients at risk for hypotension and bronchospasm o Least soluble = Fastest: Nitrous Oxide, Desflurane,
o Indirect sympathomimetic activity Sevoflurane, Isoflurane, Halothane
o support BP on induction → ↑ MAP, HR, CO - High solubility → distributes in tissues → slower equilibrium
o potent bronchodilator Elimination
- ↑ myocardial O2 consumptioin - For agents with low blood and tissue solubility, recovery is fast,
- Metabolized to norketamine regardless of duration of anesthetic administration
- CATALEPTIC STATE - For inhalation agents w/ high blood and tissue solubility, recovery
o profound analgesia, unresponsiveness to commands, breathe will be function of the duration of anesthetic administration
spontaneously, amnesia, eyes open, nystagmus with pupillary - Accumulated amounts of anesthetic in the fat reservoir will
dilation, salivation, lacrimation, and spontaneous limb prevent blood(and therefore alveolar) partial pressures from
movements → DISSOCIATIVE ANESTHESIA falling rapidly
o Give atropine first – muscarinic antagonist → decreases
salivary secretions ISOFLURANE
- Nervous system: ↑ CBPF, ICP - Pungent odor, airway irritant, and can stimulate airway reflexes
o Emergence of delirium: hallucinations, vivid dreams, and during induction of anesthesia
delusions that can be reduced by giving benzodiazepene o coughing & laryngospasm
o Usually MEDAZOLAM → forgets dreams o Can use when patient is asleep
- Induction and recovery: faster
BARBITURATES - Relaxes uterine smooth muscle – not recommended for analgesia
- Sodium thiopental – induce anesthesia or anesthesia for labor and vaginal delivery
- Thiamylal – veterinary use o Used to deliver placenta
- Methohexital – px for electroconvulsive therapy o Then decrease when placenta is delivered to contract uterus
→ stops bleeding
- ↓ CMR, CBF, ICP anticonvulsant effect
- higher incidence of wheezing in asthmatics (histamine release) SEVOFLURANE
- Contraindicated in px with acute intermittent or variegate - Pleasant smell, rapid onset, lack of irritation to the airway
porphyria – can induce fatal attacks o preferred for inhalation induction
- Induce aminolevulinic acid synthase - Can undergo an exothermic reaction w/ dessicated CO2 absorbent
o an enzyme responsible for phorphobilinogen synthesis – (BARALYME) to produce airway burns or spontaneous ignition,
excessive phorphobilinogen levels explosion and fire

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LECTURE NOTES – GENERAL ANESTHESIA (DR. CORPORAL) 4
- SHOULD NOT be used in anesthesia machine in w/c CO2 absorbent o Megaloblastic anemia & peripheral neuropathy
has been dried by prolonged gas flow through absorbent – can - It will exchange N2 in any air-containing cavity in the body → N2O
also produce CO will enter the cavity faster than nitrogen escapes
- Used for Out-patient surgery - Contraindicated in px w/: expanding pneumothorax, obstructed
- (-) tachycardia- prefer for px prone to myocardial ischemia middle ear, air embolus, obstructed loop of bowel, intraocular air
- Potent bronchodilator bubble, pulmonary bulla,intracranial air
Metabolism: CYP2E1
- Byproduct: hexafluoroisopropanol; inorganic fluoride ANESTHETIC ADJUNCTS (nice to know)
- COMPOUND A (pentafluoroisopropenyl fluromethyl ester)
o potentially nephrotoxic Benzodiazepines: Midazolam, a2-adrenergic agonists:
- FDA recommends: Sevoflurane be administered w/ fresh gas flows Diazepam, Lorazepam Dexmedotomidine
of 1-2 Lithium w/ 2 MAC-hours to minimize exposure to *Anxiolysis, amnesia, sedation – *Shorter (<24hrs) sedation of
compound A prior to induction of anesthesia critically ill adults
*sedation during procedures not *Sedation, analgesia, little
DESFLURANE requiring general anesthesia respiratory depression
- Requires use of specially heated vaporizer that delivers pure vapor *Used for intubation postop
- Very low blood:gas partition coefficient (0.42) and not very soluble *S/E: hypotension, bradycardia
in fat Analgesics: NSAIDs, COX-2 Neuromuscular blocking agents
o Alveolar & blood conc rapidly rise to level of inspired Inhibitors, acetaminophen,
concentration Opioids (fentanyl, meperidine,
- Induction and recovery: very fast – used for OPD morphine)
- Irritates the tracheobronchial tree *Reduce aesthetic requirements *Depolarizing muscle relaxant:
o coughing, salivation & bronchospasm & minimize hemodynamic succinylcholine → trigger
Metabolism: CYPs changes produced by painful malignant hyperthermia
- By product: Trifluoroacetic acid stimuli *Nondepolarizing muscle
- Anesthesia machine with dessicated CO2 absorbent: can produce *Opioids- acts on u receptors relaxants: Atracurium,
greatest  Carbon Monoxide (CO) Cisatracurium, Rocuronium
*immobility
HALOTHANE *antagonist for depolarizing
- Stored in amber bottles with thymol as preservative muscle relaxant: NEOSTIGMINE
o Light-sensitive subject to spontaneous breakdown or EDROPHONIUM +
- Bronchodilator Glycopyrrolate or Atropine
- Sensitize the myocardium to the arrhythmogenic effects of (offset muscarinic activation)
epinephrine
-  ICP especially in px w/ space-occupying intracranial masses OXYGEN
- 21% of air
*Halothane-induced hepatic necrosis - Sea level represents a partial pressure 21 kPA (158 mm Hg)
o Biotransformation by CYP → produce trifluoroacetic acid - Higher altitude = ↓ atmospheric pressure = ↓Partial pressure of
o Trifluoroacetylcholine- alter proteins O2 (PO2)
o Fever, anorexia, nausea, vomiting, rash, peripheral - Partial pressure drives the diffusion of O2
eosinophilia, hepatic failure - Elevated altitude: ↓ uptake and delivery of O2 to tissues
o Fatality rate (50%) o Compensatory mechanism: Polycythemia (↑Hgb)
- HYPERBARIC THERAPY: ↑ atmospheric pressure
ENFLURANE o ↑ PO2 and uptake and delivery of O2 to tissues
- Mild, sweet odor o Used for Bends
- By product: Fluoride - Blood: O2 carried byhemoglobin
- Patient taking isoniazid: enhanced metabolism of enflurane - Hemoglobin binds to 1.38ml of O2 per gram
- bronchodilator - Sigmoidal oxyhemoglobin dissociation curve
- Unsual property of producing Electrical seizure activity - Shift to the right:
o ↑ temp, ↑ PCO2, ↓pH, ↓affinity to O2 (delivers O2 where it
NITROUS OXIDE is needed)
- Colorless, odorless gas - Shift to the left:
- Very insoluble in blood and other tissues o ↑ affinity to O2
o Rapid induction and emergence
- “SECOND GAS EFFECT” Effects of Hypoxia
o concentrate co-administered halogenated anesthetics - marked alteration in gene expression, mediated in part by hypoxia
o on discontinuation of N2O administration, nitrous oxide gas inducible factor-1a
can diffuse from blood to the alveoli diluting O2 in the lung → - Cessation of aerobic metabolism
DIFFUSIONAL HYPOXIA - Exhaustion of high energy intracellular stores
o To avoid hypoxia, 100% O2 rather than air should be - Cellular dysfunction
administered when N2) is discontinued - Death
- N2O can oxidize Cobalt of vit B12
o preventing vit B12 from acting as a cofactor for methionine Oxygen administration:
synthesis → vit B12 deficiency - Nasal Cannula: 24-28% FIO2 at 2-3L/min – max: 40% FIO2

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LECTURE NOTES – GENERAL ANESTHESIA (DR. CORPORAL) 5
- Face mask: max: 60% at 6-15 L/min to >85% by adding a 600- o can result from oxygen toxicity or relative hypoxia
1000mL reservoir bag
- Cyanosis: 5g/dL of deoxyhgb is present in arterial blood End table
- Normal hgb: 67% saturation - Laparoscopy – insufflate CO2
- Anemia: 50% O2 saturation - Nitric oxide – inhaled NO is used to dilate pulmonary vasculature
in persistent pulmonary hypertension in the newborn
Oxygen toxicity - Helium – pulmonary function testing, treatment of respiratory
- Retinopathy of prematurity (ROP) obstruction
o eye disease in premature infants involving abnormal
vascularization of the developing retina

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LECTURE NOTES – GENERAL ANESTHESIA (DR. CORPORAL) 6

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