Regional and Anatomy

Epidural fat causes opioid sequestration: lipid soluble opioids such as fentanyl and sufentanil have decreased net transfer from epidural to intrathecal space. Lipid solubility reduces bioavailability.

Similarly, etidocaine, which is 7x more potent than lidocaine but more lipid soluble, is effective equipotent in the epidural space. 

• CSF volume is 100-160ml in adults and produced 500ml/day. CSF has very little movement and does not distribute drugs effectively. 

• Spinal cord extends to sacrum in utero and shrinks to L3 at birth to L1 as an adult. Spinal cord gives off 31 pairs of spinal nerves that are made up of an anterior motor root and posterior sensory root. T1-L2 intermediolateral gray matter contains cell bodies of preganglionic sympathetic neurons. 
• Epidural test dose with 3ml of local anesthetic containing 1:200,000 of epinephrine is used to detect increase in HR of 30 in 30. Pts who are beta-blocked may use BP elevation of >20mmHg. Women in labor who have natural HR elevations 2/2 contractions can use isoproterenol. 

Baricity and Positioning is the ratio of the density of a local anesthetic solution divided by density of CSF. Baricity affects block height and thoracic blocks can be achieved with hyperbaric solution in supine or trendelenberg positioning. Hypobaric with sitting position is not used because it results in too high of a block. Saddle blocks can be achieved with hyperbaric solution in sitting or hypobaric in prone. Hypobaric solution given in lateral supine position is also useful as unilateral block on the upward side. Distribution by gravity becomes fixed after enough dilution in CSF (can take 60 minutes). Isobaric solutions tend to have variable block concentrated in the lower thoracic. 

Dose, volume, and concentration

In isobaric solutions: Volume and concentration have no effect. Lower total dose can produce lower blocks (at least in bupivacaine but not tetracaine).

In hyperbaric solutions: positioning is king. But lower total doses again produces lower blocks in bupivacaine but not tetracaine (2.5 dermatomes lower). 

Dosing does affect duration of block with larger doses creating longer blocks. 

Injection site

Only in isobaric solutions does this matter. Decreasing injection site by 1 vertebrae can lower height by 2 dermatomes with bupivacaine.

• CSF volume down (higher block) - pregnancy, older, kyphoscoliosis, ascites (engorgement of epidural veins). Obesity increase CSF volume!
• Adding fentanyl to spinal quickens onset and deepens sensory block
• Intrathecal fentanyl compared to morphine: less respiratory depression, less urinary retention, less n/v
• Chassaignac's tubercle is C6 transverse process, which is the landmark for stellate ganglion block. Remember stellate ganglion is C7-T1 ganglion but you can't inject directly because overly vertebral artery.
• Infraclavicular is most dangerous for pneumothorax and chylothorax
• Axillary block has 3 nerves surrounding the axillary artery. The one across from the artery is radial, and one closest is median. Remember to block musculocutaneous nerve and also intercostobrachial nerves.
• Medial knee is covered obturator nerve
• Remember peroneal nerve wraps around lateral fibula, while tibial is medial to that
• 5 nerves in ankle block, superficial peroneal, deep peroneal, sural, tibial, and femoral

Anatomy
V3 - Anterior Tongue
IX - Posterior Tongue, Soft palate, oropharynx,
Internal branch of X - Hypopharynx above VC, VC
Recurrent branch of X - VC, Larynx, Trachea

Celiac plexus at L1
Artery of Adamkiewicz T8-L1

Hypertensive Meds

Labetalol:
blocks ₁-, ₁-, and ₂-receptors. The ratio of -blockade to -blockade has been estimated to be approximately 1:7. Reduction in BP w/o change in HR or CO. Onset 5 min, halflife 5 hours

B-blockers:
Atenolol excreted unchanged by kidney. Metoprolol, propranolol, labetalol have hepatic metabolism. Esmolol is metabolized by RBC esterases.
Esmolol has half life of 9min

POISE trial
8000 patients with CAD received metoprolol XL before surgery continued for 30 days. Decreased MI but increased mortality and stroke.

Pheo:
Avoid sux as abdominal fasciculates could release catecholamines. Ketamine should be avoided as it is sympathomimetic. Halothine potentiates dysrhythmias of epineprhine. Histamine release provokes catecholamines so no atracurium. Neuroaxial techniques block postganglionic discharge of catecholamines but do not block receptors so pheo still active. Chronic elevations of catecholamines can lead to cerebral hemorrhage, renal failure, heart failure, MI, dysrhythmias.

Hypotensive Meds

Norepinephrine receptors are G-protein linked and divided into a1, a2, b1, b2
a1 - raises intracellular calcium: vasoconstriction, mydriasis, uterine contraction, sphincter contraction
a2 - presynaptic endings, inhibits adenylate cyclase: vasodilatation, sedation, less addiction?
b1 - activates adenylate cyclase: positive chronotropy, dromotropy, inotropy
b2 - epi > norepi, activates adenylate cyclase: bronchodilation, vasodilation, tocolysis

Norepinephrine's action in the synapse is terminated by
1. Reuptake by postganglionic nerve ending (inhibited by TCA)
2. Diffussion by receptor sites
3. Metabolism by MAO and COMT (inhibited by entacapone, tolcapone, nitecapone)

Phenylephrine:
Continuous infusion (100 mcg/mL at a rate of 0.25–1 mcg/kg/min). Gradual tachyphylaxis

Epinephrine:
Used for vfib (50mcg to 1mg) and anaphylaxis (100-500mcg bolus followed by infusion). Volatile anesthetics such as halothane potentitate dysrhythmic effects of epinephrine.
Continuous infusion (4 mcg/ml at rate of 2-20mcg/min)

Norepinephrine:
Bolus (0.1 mcg/kg) followed by infusion at rate of 2–20 mcg/min

Ephedrine:
Used in obstetrics because does not decrease uterine Q. Non-catecholamine so longer-lasting. Some antiemetic properties particularly 2/2 hypotension from neuroaxial injections

Dopamine
1-20 mcg/kg/min infusion

Dobutamine
2-20 mcg/kg/min infusion

Clondine and Precedex:
A2 agonists, sedative, analagesic, sympatholytic effects. Reduces anesthetic requirements. Abrupt withdrawal leads to hypertensive crisis.
dexmedetomidine loading dose 1 mcg/kg over 10 min followed by an infusion at 0.2–0.7 mcg/kg/hr
Clonidine oral (3–5 mcg/kg), intramuscular (2 mcg/kg), intravenous (1–3 mcg/kg)

b1,b2 are G-proteins that stimulates adenyl cyclase increasing cAMP, which activates protein kinase A, which increases intracellular calcium

a1 is also a G-protein that stimulates phospholipase C which also increases calcium

NO stimulates guanyl cyclase and increases cGMP

Phosphodiesterases break down cAMP and cGMP, PDE5-I such as viagra causes increase in cGMP and PDE3-I such as milrinone causes increase in cAMP. Theophylline and Aminophylline are nonselective PDE-I

Opioids/NSAIDs

Alfentanil has lower lipid solubility than fentanyl but higher non-ionized fraction so it works really fast. 

All opioids can be retained by the lungs (first-pase uptake) and then redistribute once systemic concentrations fall.

Opioids have context-sensitive halflife because blood concentration is decreased from redistribution at small doses and biotransformation at large doses.

Normeperidine can cause seizures. Norfentanyl is nonactive but used to determine abuse. Codeine is a prodrug that has variable biotransformation depending on CYP enzymes. Pseudocholinesterase deficiency does not affect esmolol or remi. Both meperidine and morphine metabolites are excreted in urine. Alfentanil biotransformation is impaired by erythromycin

Meperidine has atropine-like affects (tachycardia) and causes cardiodepression unlike other opioids. Meperidine, hydromorphone, and morphine evoke histamine release and bronchospasm (benzylisoquinolones). Fentanyl-like opioids induce chest wall rigidity.

APNEIC THRESHOLD - greatest PaCO2 at which a patient remains apneic increases with opioids.

Opioids decrease CMRO2, cerebral q and volume, ICP but less than barbiturates, propofol, or benzos

NSAIDS inhibit COX, which catalyzes the production of prostaglandin H1, a key mediator of inflammation. COX2 is less selective than COX1 purely by size (ie. a bigger molecule fits in COX2 but not COX1). COX1 is widely distributed in the body and COX2 is made for inflammation. COX2 decreases the risk of platelet dysfunction but causes increased thrombosis.