Myotoxicity of Local Anesthetics: Implications for Pain Pumps
In a recent article entitled, Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles, Padera, et.al., state:
Myotoxicity is a well-recognized side effect of local anesthetic administration, perhaps particularly of extended exposure, whether from controlled-release methodologies or from catheter-related methods. Occasionally, the consequences can be clinically significant.
These authors studied a variety of controlled-release systems designed to prolong the duration of local anesthetics. The authors gave rats sciatic nerve blocks by injecting them with different bupivacaine solutions and found muscle damage in all of the animals, with greater damage from the encapsulated (higher concentrated) bupivacaine particles than from free bupivacaine (the 0.5% bupivacaine hydrochloride solution commonly used in surgeries). Local anesthetic-induced myotoxicity generally recovers rapidly, often within two weeks, however, the authors noted some controlled-release formulations cause myotoxicity at least as far out as one month after injection.
One possible explanation of this observation is that local anesthetic myotoxicity is time-dependent. Myotoxicity was found to increase with the concentration of bupivacaine, but also markedly with duration of exposure. For example, 62 +/- 12% of cells exposed to 0.025% bupivacaine survived a 2-hour exposure, whereas only 1 +/- 2% survived at 3 weeks. It is important to note that this is an extremely weak concentration of bupivacaine: twenty times weaker than 0.5%. The authors go on to say:
This finding raises the possibility that myotoxicity could be an inevitable concomitant of long-term exposure to conventional (amino-amide and amino-ester) local anesthetics, irrespective of the technology used to deliver them. Myotoxicity is a well-known occurrence in clinical or investigational use of conventional local anesthetics. Although it can have severe consequences, it has not generated much clinical concern. In fact, intramuscular local anesthetic injection is a standard treatment for trigger points in myofascial pain syndromes, and local anesthetic myotoxicity is generally reversible. The distinction that must be made, however, is that those treatments generally involve a single-shot drug injection with a brief duration, whereas microparticulate systems can result in very high local concentrations and/or weeks of local anesthetic exposures.
The findings of this article raise alarming concerns about pain pumps. The continuous repeated exposure to tissues (especially around a healing surgical wound) with local anesthetics (known to cause cell damage and even death) over a period of 48 to 120 hours seems much more likely to result in cell damage than if the same volume of the medication was injected at a single time.
The potential for irreversible cell damage—necrosis—caused by local anesthetics and infusion pumps seems site-dependent. Pain pump manufacturers have acknowledged as much. I-Flow, in its current Directions For Use for the On-Q pump states:
To avoid complications in restrictive spaces use the lowest flow rate, volume and drug concentration required to produce the desired result. In particular:
Avoid placing the catheter in the distal end of extremities (such as nose, ears, fingers, groin area, penis, toes, etc.) where fluid may build up as this may lead to ischemic injury or necrosis.
However, this warning (also contained in I-Flow’s Technical Bulletin on hand and foot surgery) is too limited in scope. While it would apply to bunionectomies, it does not apply to any other foot or ankle surgeries, including catheter placements in the top of the foot near the ankle. This is certainly a restrictive space, made even more so when it is under a compression dressing following surgery. Two pain pump cases I have involve foot surgeries with catheter placements in this location, with disastrous complications to the patients.
The more often I read about the toxicity of local anesthetics, especially bupivacaine, the more I suspect it routinely causes damage to the patient (maybe always causes damage), but that harm is often not detected because the affected cells regenerate or scarring or other damage occurs which may not manifest itself until far in the future. Even when the damage arises to visible injury, many of these injuries are not properly diagnosed as local anesthetic tissue toxicity, but rather as post-operative infections. This is what occurred in the two foot surgery cases I mentioned above.
