The only physical and chemical properties of opioids that best determine their action as spinal anesthetics is lipid solubility.
Many of the effects of opioids introduced into the epidural space, both desirable (analgesia) and undesirable (complications), strongly depend on the hydrophilicity (better water solubility) or lipophilicity (better solubility in fats) of their molecules.
Fentanyl — a lipophilic opioid — easily overcomes biological barriers (all membranes are “built” of lipids), quickly passes through the dura mater and, having barely reached the cerebrospinal fluid, is well absorbed by the roots and the spinal cord itself — by its segments, near which it was inserted. But it just as easily returns to the epidural space when its concentration decreases there. And this happens quickly, because it also passes very easily through the vascular wall.Therefore, firstly , its concentration in the blood rapidly increases (as after intramuscular administration), secondly, it does not linger long either in the epidural space or in the spinal cord. Therefore, some authors believe that epidural administration of opioids with high lipid solubility (like fentanyl) has few advantages over the intramuscular or intravenous route: both general effects are the same (including rapid respiratory depression), and local effects are short-lived [ WDNKee et al., I996. His epidural introduction is justified either for operations with a small incision at the level of two or three dermatomes (thoracogomy) —and it must be inserted in the same segments (Table 28), or for pain relief after such operations — with a catheter tip against the same segments, and Fentanyl is better administered by infusion.
Morphine — a hydrophilic opioid — passes through the dura mater slowly but surely. Once in the liquor, due to its hydrophilicity, it remains there for a long time and slowly diffuses below and above the site of administration, reducing the perception of pain in many segments. On the one hand, this was the reason for its widespread use for prolonged (up to a day) anesthesia for infrequent, even one-time, administration — as after any operations, and outside of surgery — in incurable cancer patients. Unfortunately, morphine, as an opioid with low solubility in lipids, can be the cause of “cunning” delayed apnea — even almost a day later.