Pain Pump Law Blog : Medical Device and Malpractice Lawyer & Attorney for Local Anesthetic Infusion Pump & Post-Operative Infection Cases

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.

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A number of articles have reported a relationship between local anesthetics and myotoxicity—damage to muscle; for example: Zink, et.al. (2004), Zink, et.al. (2003), Irwin et.al., (2002), Nonaka, et.al. (1983). Published before the widespread use of pain pumps, a 1994 article by Hogan, et.al., begins with the following accepted generalizations:

All local anesthetics that have been tested are myotoxic. Procaine produces the least and bupivacaine the most severe injury. Injection of local anesthetics intramuscularly or into adjacent subcutaneous tissue results in myonecrosis. The extent of muscle injury from local anesthetics is dose dependent and worsens with serial administration.

Local anesthetics are injected into muscle for treatment of myofascial pain, in wound margins during surgery, and for neural blockage during surgical anesthesia.

The authors describe a female patient who underwent capsular release of the left shoulder. Because continuous passive shoulder motion and physical therapy were planned immediately following the surgery, a nerve block during and after the procedure was planned. A catheter was placed in the left interscalene groove at the level of the cricoid cartilage. Bupivacaine (0.5%) with epinephrine was injected incrementally to a total volume of 45 ml (200mg), producing sensory and motor blockade of the shoulder, arm, and hand.

When the woman began experiencing shoulder pain approximately 16 hours post-operatively, she received additional bolus doses of the 0.5% bupivacaine with epinephrine through the catheter. The doctors used additional injections of the same solution through the catheter when the woman’s shoulder pain did not resolve. After 34 hours, the catheter was removed. The total dose was 228 ml (1140 mg). The woman developed persistent pain in the left side of her neck. Imaging was suggestive of a tissue injury.  Approximately 8 weeks post-op, a muscle biopsy  showed injury to the muscle fibers.

Large doses of bupivacaine were used on the patient because of the authors’ desire to provide pain relief suitable for the expected post-operative manipulations of her shoulder. Because the injections failed to produce the desired effect, they suspected the catheter tip became dislodged.

According to the authors, while myotoxicity of local anesthetics has been widely produced in experimental settings, reports in human patients are uncommon. The authors’ next observations are why this article is interesting regarding pain pumps:

Local anesthetic injection for neural blocks only occasionally requires intramuscular injections of large volumes…. These are not usually repeated, and the injection site is difficult to examine. Small volumes are used with injections for intercostal, supraspinatus or musculocutaneous nerve blocks and with trigger point injections and stellate ganglion blocks.

Because experimental studies show myonecrosis after single injections of even minimal doses of local anesthetic, it is likely that myopathy occurs after most injections but is not recognized because of rapid and complete recovery.

Local pain for which trigger point injections are performed may disguise myopathic changes, and discomfort and dysfunction after injections performed for surgical anesthesia can be readily attributed to surgery or concealed by surgical pain. Splinting prevents tenderness from being identified. The pain of inflammation develops only after 3 or 4 days, and the appearance of atrophy takes longer; thus, these events frequently may be missed or not correlated to the administration of anesthetic agents. (My emphases)

Caveats: this 1994 article pre-dates the widespread use of pain pumps.  The authors utilized Bupivacaine (0.5%) with epinephrine. Several years ago, pain pump manufacturers began recommending against using local anesthetics with epinephrine. Further, the large volume of Bupivacaine injected into the woman’s shoulder undoubtedly exceeded the manufacturer of Bupivacaine’s maximum recommended dose of 400 mg within a 24-hour period. In light of the numerous recent reports of chondrolysis, the fact that such a large volume of Bupivacaine with epinephrine was injected into the woman’s shoulder near cartilage is alarming (although the authors seem to believe that the catheter had become dislodged from its original location).

Nonetheless, the article raises a number of concerns regarding continuously infused local anesthetics and pain pumps.  As the authors’ comments make clear, at the time this article was written, local anesthetics were typically used in relatively small amounts around the surgical site and to produce nerve blocks.   Even small amounts, however, routinely cause cells to die, but they typically regenerate without incident. Post-operative pain and inflammation often mask symptoms that may actually be associated with damage to tissues.

In small amounts, given the beneficial pain relief afforded by local anesthetics, the temporary harm they cause would seem to be an acceptable side effect.  What happens, though, when these drugs are continuously infused, in or near an open wound, in total volumes larger than commonly used in the past?   There must be factors that cause the usually temporary harm to tissues to take the form of more visible and potentially permanent complications such as wound dehiscence, blistering, sloughing, and necrosis.  These would seem to include:

• Local anesthetic volume
• Local anesthetic concentration
• Rate of infusion
• Duration of infusion
• Surgery/catheter site
• Patient-specific factors-age, weight, risk-factors

The pain pump and local anesthetic manufacturers have failed to properly considered these factors and, instead, make blanket, one-size fits all recommendations to surgeons. 

A bigger question:  Why is the medical community still so routinely using higher concentrations of Bupivacaine when it is known to cause damage to a variety of human cells-- cartilage, muscle, nerve, renal, and undoubtedly others?

 

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In a 2004 Product Insert, I-Flow Corporation stated its On-Q PainBuster was intended to provide continuous infusion of a local anesthetic directly into an intra-operative site for post-operative pain relief. By April 2009, I-Flow had modified this language to say that the product is intended to provide continuous deliver of medication (such as local anesthetics) to or around surgical wound sites and/or close proximity to nerves for pre-operative, peri-operative and post-operative regional anesthesia and/or pain management.

This seemingly minor change is significant because it is indicative of potential problems with pain pump catheters being placed directly into a surgical site. (Although images from I-Flow's most recent product materials still show the catheter being inserted directly into the wound site).

In 2003, Brower and Johnson published an article entitled Adverse Effects of Local Anesthetic Infiltration on Wound-Healing.  As background they explain:

Wound infiltration with LA (local anesthetics) can provide excellent analgesia under at least some circumstances, although optimal dose and wound installation technique are not well-defined. However, there is a substantial body of literature suggesting that LA infiltration can have deleterious effects on wound healing. These reports are spread across a wide range of literature, including surgical, anesthetic, ophthalmologic, pharmacologic, and cellular bio-chemistry and are often not appreciate in total. The risks reported therein should be considered in clinical decisions to use wound infiltration and in future studies to assess its benefits.

In reviewing the available studies on the effects of local anesthetics on wound healing, the authors report a number of noteworthy conclusions:

Overall wound healing may also be affected by any effect of LA on a cell type adjacent to the wound. In particular, myotoxicity from local infiltration of LA, particularly bupivacaine, could weaken the wound site even if fibroblasts and other cells directly involved in wound healing were not affected.
Taken together with the body of published studies discussed here strongly suggests that LAs can inhibit the first two stages of wound healing, the inflammatory and granulation/proliferation stages. Inhibition of healing appears to be a general property of all commercially available LAs.

Pain pump manufacturers want surgeons to be able to place catheters directly into the wound site because it is easier to visualize than placement for a nerve block, which might require an anesthesiologist. These devices are marketed to surgeons, in no small part, as means for them to perform (and bill for) an additional procedure on their own. The wound healing problems raised by Brower and Johnson seem quite consistent with the sorts of adverse events involving pain pumps (beyond chondrolysis) that have been reported to the FDA.

Perhaps if the local anesthetic is not directly bathing the surgical wound, but an area proximate to it, the patient can still receive pain relief at this site without negatively affecting wound healing. I am aware of cases, however, in which the catheter was placed some distance to the surgical site and severe wound healing complications developed anyway. It is possible these instances had more to do with the location of the surgeries--the dorsum (top) of the foot--than whether the catheter was placed in or out of the incision.

More positive perspectives on local anesthetic infusion directly into a surgical wound site include portions of a book chapter by Rawal (2006) (PDF) and an editorial by Kehet and Liu (2007) (PDF).

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The controversy and litigation over local anesthetic infusion pumps—pain pumps—has to date largely been focused on shoulder surgeries and chondrolysis. There is a perception that these devices were intended by their manufacturers for use primarily in the shoulder. I have seen some complaints and discovery documents from plaintiffs lawyers even refer to these devices as “shoulder pain pumps.”

In fact, these devices have been and continue to be routinely used in surgeries throughout the body. What hasn’t received sufficient attention is the fact that numerous adverse events involving types of surgery other than to the shoulder have been reported for many years, including prior to the problem of chondrolysis in the shoulder being identified with these devices.

In 2004, two FDA researchers published a journal article, Local Anesthetic Infusion Pump Systems Adverse Events Reported to the Food and Drug Administration. They summarized 40 injuries reported to the FDA that followed the use of pain pumps at a variety of surgical sites including orthopedic, gastrointestinal, and podiatric. The complications encountered with the pain pumps included tissue necrosis, surgical wound infection, and cellulitis. 45% of the surgeries were orthopedic, typically total knee replacements. 20% were for podiatric surgeries, including bunionectomies, plantar fasciotiomies, and others.

All of the reports that specified the local anesthetic involved Bupivacaine (most common trade name—Marcaine) with or without adrenaline. The consequences of these adverse events were typically severe and required intervention and additional medical and surgical treatment. The authors’ review of the literature found little had been written to support a causal link between pain pumps and the complications that had been reported to the FDA. Therefore, the authors’ conclusion was tentative and stated the reports may represent sentinel events, i.e., an early warning that is representative of a widespread problem, or alternatively, these may be isolated incidents.

The FDA Medical Device adverse event database shows that at least 60 additional adverse events involving tissue necrosis and other wound-healing complications and pain pumps manufactured by I-Flow Corporation (the largest manufacturer of pain pumps) alone have been reported to the FDA since December 2003, the end-point of the article’s scope. It seems likely these events are not isolated and indicate a serious problem with these devices, beyond their likely relationship to chondrolysis in shoulder surgeries. There is a substantial body of evidence that Bupivacaine, even without epinephrine, causes severe damage to a variety of human tissue including muscle, subcutaneous skin, as well as cartilage.

Prior to the advent of pain pumps, local anesthetics were typically used in relatively small amounts to provide nerve blocks or in the margins of surgical wounds to provide pain relief. Even if harm to tissues occurred it likely went unnoticed because cells damaged by local anesthetics typically regenerate and surgical pain and dressings may have masked such harm. Pain pumps infuse much larger volumes of these drugs, which appears to be especially problematic in certain areas of the body such as joint spaces--shoulder and knee--and the foot.

I believe pain pump manufacturers have improperly relied on the dose and concentration recommendations made by the makers of Bupivacaine for past uses, without adequate research to support its safe use when continuously infused in larger volumes. Even when pain pump manufacturers have been confronted with evidence of adverse events involving their products, they have failed to adequately warn surgeons and the public of these risks. It is likely that hundreds of patients, if not more, have suffered injuries, many life-altering, as a result.

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