Finishing up of General Anesthetics and Local Anesthetics

Degradation of CO₂ Absorbers:

Degradation of CO₂ absorbers (barolime or soda lime) produces Compound A (pentafluroisopropenyl fluromethylether). It is not a metabolism product, but degradation. This is unique to sevoflurane. Compound A and fluoride are both nephrotoxic in rats, and quite possibly humans at large quantities. A wide variety of patients have been exposed to both sevofluorane and compound A and their kidney function did not change. Compound A forms glutathione conjugates in the liver, mediated by beta lyase of the Cytochrome P-450 microsomal superfamily of isozymes. This is an enzyme in the kidney. The nephrotoxicity was found during research on rats, where the beta lyase works 10X better than in humans, so compound A’s degradation product sevofluorane doesn’t seem to be a problem in humans even though it showed that result in rats.

Local and Regional Anesthetics

There are two classes of local’s. They are either amides or esters. Every local has both a hydrophobic and hydrophilic part. The hydrophobic part is generally a ring structure and the hydrophilic is generally an acid. Between the two is either the amide or ester bond. When you are asked to distinguish an amide from an ester, you just need to look at the nomenclature. All locals are –caine’s. On the generic name of the drug, if there’s the letter “I” anywhere in the name before “-caine,” it’s an amide. Let’s practice: lidocaine = amide. Bupivicaine = amide, cocaine = ester, procaine = ester, (xylocaine) = amide because (xylocaine) is a brand name; (xylocaine) is the brand name for lidocaine.

Locals are often mixed with other agents like preservatives, or epinephrine for vasoconstriction. Locals given alone are called plain, and those given with epi are called a local anesthetic with epinephrine. You must be careful when using epi. Epi will aid the anesthetic by increasing its duration of action because locals are generally weakened by diffusion, but epi will hold the drug in place longer because of its vasoconstricting capabilities. Epi is generally used because it will make the drug last longer and decrease bleeding (which can be both a + because it will decrease bleeding around a wound, and a – because you may not recognize any “bleeders” before you tie off the incision, causing a hematoma under the skin later when the epi wears off.) A negative aspect of epi is if it is used in terminal circulation like fingers, toes, ear cartilage, nose you may cut off the only circulation to the area. Although true allergies are extremely rare many patients will claim to be allergic to “novocaine” (which contrary to many med student’s beliefs is not used anymore) but they are just uncomfortable when feeling the natural effects of epinephrine, so make sure you ask your patients what symptoms they experience when they were given the local anesthetic.

Locals tend to be toxic. 2% lidocaine is 20mg/mL. If the toxicity for lidocaine is 5-7 mg per Kg body weight of patient (70 kg patient needs about 350 - 490 mg of lidocaine to be toxic, that’s 17.5 - 24.5 mL of 2% lidocaine or 10 – 14.5 carpules for all you mathematically challenged), you must be careful how much is given, because depending on how quickly it diffuses throughout the body, some major damage can be done. Like other drugs, locals have varying levels of diffusion and pharmacology. However, toxicity and duration of action go hand in hand with locals. Drugs that are short acting are generally nontoxic. Nessicaine and chlorprocaine can be given very rapidly but because it is “broken up so quickly we can’t even give enough of it to create toxicity.” Longer acting drugs can produce toxicity. Bupivicaine is not even given in ¾% strength anymore because there were too many problems with toxicity.

Toxicity for locals involve CNS and the heart. The major problem for these generally arise when they are accidentally given in the wrong location. For example, when an epidural is given but the needle is putting anesthetic into the epidural vein. To prevent this a test dose is given to make sure the dose is given into the epidural space. Using an epidural as our example, to make sure that the injection is being placed in the correct location, a small injection is given in the epidural space. If the patient says they have a feeling of impending doom, that their heart is racing, they don’t think they’re breathing right (even though they generally are), the test dose was given into the epidural vein. This is fine, because the response lasts about 20 seconds, while adjustments are made in the site of injection. A second test dose can then be given, and after no response, the anesthetic is given. This actually happens kind of frequently.

Poisons This also explains how Locals work:

Tetrodotoxin (TTX) and saxotoxin. They generally occur in Japanese puffer fish. They block Na channels, inhibiting axonal conduction. They are two of the most potent poisons known. The duration of action of these NMJ blockers are similar to anesthetics, except that their mechanism of action is for days to weeks. If someone eats puffer fish that is not properly prepared, they can be ventilated with hemodynamic support for a week or two until the poison is metabolized. Locals are much quicker in action by comparison so they can be given therapeutically when not given systemically.

Category: Anesthesia Notes