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

I am working on another post relating to FDA regulation of pain pumps, but expect it may be a week or two before I am able to complete it.  In the meantime, I thought I would share an article I recently came across----Disposable Infusion Pumps by Skryabina and Dunn.  It contains useful explanations of how some of the most common types of these pumps actually function.

These devices are used for many purposes beyond that of a "pain pump"--delivering local anesthetics post-operatively at or near a surgical site.  These include the delivery of other medications, including chemotherapy, antimicrobials, antibiotics, as well as the delivery of anesthetics or analgesics by other routes, eg., continuous epidural, peripheral nerve block, and i.v..  The authors provide concise descriptions of the mechanisms of several types of non-electric pumps including elastomeric, positive-pressure (spring-powered and gas-pressured powered), negative-pressure (vacuum), and patient-controlled analgesia (PCA) pumps. 

The flow rates of medications through disposable pumps are significantly inaccurate--typically within +/-15% or even +/-20%.  (Compared to +/-3% with electronic syringe pumps and +/-5% with electronic volumetric pumps).  I believe most pain pump manufacturers include the +/-15% figures in their written materials--see, eg. the flow rate table included in the product Insert for the On-Q Pump with Fixed Flow Rate. 

Nonetheless, I assume most surgeons who use a pain pump labeled with a 2 ml/hr flow rate are likely to believe that the device delivers only 48 ml of local anesthetic in the first 24 hours.  In fact, the same flow rate table in the Insert for the On-Q Pump (along with all other documents for the On-Q I've seen) shows that a 100 ml pump will actually deliver 65 ml in the first 24 hours.  For the first several hours, the flow rate is actually 2.5 ml or higher. 

If the anesthetic is 0.50% Marcaine, 65 ml means 325 mg.  The maximum 24 hour dose for Marcaine is 400 mg and, as I've stressed before, this is based on the risk of systemtic toxicity (neurological or cardiac) and not local (tissue) toxicity.  Surgeons commonly use additional injections of local anesthetics around surgical sites during procedures.  Thus, it would take only an additional 15 ml of 0.50% Marcaine, along with a 100 ml 2 ml/hr. pump, to reach a 400 mg dose in the first 24 hours after surgery. 

I believe many pain pump manufacturers have blithely assumed that any 24 hour dose of Marcaine as long as it remains less than 400 mg, in most any part of the body, regardless of the concentration, and regardless of the route of administration (continuous infusion vs. others), is inherently safe.  For all who have sustained injuries from pain pumps caused by local anesthetic toxicity, this has been a tragically flawed assumption. 

 

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I recently came across a post by Armand Rosetti which summarized some news articles relating to I-Flow Corporation and its Chief Executive, Donald Earhart. Especially interesting are some statements Mr. Earhart made in a November 5, 2008 conference call with investment analysts regarding the company’s third quarter earnings.  Earhart was answering questions regarding the status of the shoulder chondrolysis lawsuits, and said:

I’ve said this argument before on the conference calls, is that a pain pump or a delivery device, whether it be a syringe or one of our pumps delivering a drug, how do you blame the device, because there’s no way the device can cause the disappearance of cartilage. It would have to be whatever is delivered into the site or would have to be the technique by the doctor or would have to be the sutures or it would have to be the staples or it would have to be something else used during the surgery, but it can’t be our pump, because our pump can’t cause cartilage to disappear…. It’s like using a syringe to deliver a narcotic. We can’t be held responsible for the side effects, if I’m the syringe manufacturer, of the drug.

This raises an important point.  Clearly, it is the toxicity of the local anesthetic that causes the direct harm to the patient--whether the result be the destruction of shoulder or other joint cartilage, tissue necrosis around a surgical site, or other injury.  How then can a plaintiff reasonably seek to blame the maker of the device and not the drug?  Because a pain pump manufacturer retains a legal responsibility to patients to provide that their devices may be safely used with local anesthetics in a manner intended by the manufacturer of the local anesthetic.  Continuous infusion through a pain pump is not a listed intended use of a local anesthetic; it is an off-label use.   A statement such as I-Flow makes in its current Directions for Use for the On-Q pump, “medications or fluids must be administered per instructions provided by the drug manufacturer,” has little meaning when the use in question is not addressed by the manufacturer. 

Mr. Earhart and I-Flow appear to take for granted that continuous infusion is no different than the uses approved by the local anesthetics manufacturers. I contend pain pumps represent a categorically different use both because of the larger volume of local anesthetic infused and the significantly greater duration of exposure of the affected tissues to the medication. For example, a single bolus dose of 100 mg (20 ml) of Marcaine to produce a nerve block may well create less risk of local tissue toxicity than continuously infusing smaller volumes—2ml/hr—but with a larger total volume 240 mg (100 ml) over a much longer time—2-5 days.

On the other hand, the uses to which a syringe is put--—local infiltration around a surgery site and injections to produce various types of nerve blocks—are approved uses by the drug manufacturer.  Because there are a variety of known risks of patient injury with their devices, pain pump manufacturers have a duty  to timely and adequately convey warnings of such risks to the physicians who use them. 

 

 

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On February 19, the FDA approved a revised label for Marcaine (Bupivacaine Hydrochloride), manufactured by Hospira.  The label contains the following warning regarding the risk of chondrolysis:

Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.

This language generally seems appropriate to me, however, I fail to understand why the FDA permitted the following sentence, "There is insufficient information to determine whether shorter infusion periods are not associated with these findings."  This seems to be an ill-advised attempt by Hospira to create ambiguity about the safety of intra-articular infusion.   The FDA Alert which prompted this warning goes out of its way to note that intra-articular injections of local anesthetics in orthopedic procedures have been given for years without reported incidents of chondrolysis.  The FDA then flatly states:  Neither local anesthetics nor infusion devices are approved for an indication of continuous intra-articular infusion.

The revised Marcaine label also has the following language: 

There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. MARCAINE is not approved for this use.

Since the drug is not approved for this use, without regard to the duration of the infusion, why permit the slightest hint of confusion to remain in the label? Especially in light of the research of Constance R. Chu, M.D. that exposures even as short as 30 minutes cause massive death in cartilage cells. 

 

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In my last post, I noted the following language in the FDA's November 13, 2009 warning regarding chondrolysis and pain pumps:

Local anesthetics are approved as injections for the production of local or regional anesthesia or analgesia. The approved drug labels for local anesthetics do not include an indication for continuous intra-articular post-operative infusions or use of infusion devices such as elastomeric pumps. The FDA has not cleared any infusion devices with an indication for use in intra-articular infusions of local anesthetics. (emphasis mine)

This is an accurate and important statement:  pain pumps are an off-label use of local anesthetics. 

Someone else, likely on the side of pain pump manufacturers, seems to agree because this language is now missing from an updated version of the FDA Warning, dated February 16, 2010.  The same paragraph now reads:

Local anesthetics are approved as injections for the production of local or regional anesthesia or analgesia. Neither local anesthetics nor infusion devices are approved for an indication of continuous intra-articular infusion.

I gather that since the warning is focused on the association of chondrolysis and pain pumps, the manufacturers either disputed the statement from the FDA that pain pumps are not an approved indication for any use or contended that it was outside the scope of the warning.   The FDA is requiring pain pump manufacturers and, more importantly, local anesthetic manufacturers, to include warnings of the risk of chondrolysis with continuous intra-articular infusion.  It will be especially interesting to see the drug label changes and whether the manufacturers address the risks of continuous infusion in general and not just into joint spaces. 

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On November 13, 2009, the FDA announced it will require pain pump manufacturers and the manufacturers of the local anesthetics used in them to update their product labels to contain a warning about the risk of chondrolysis following continuous infusion with local anesthetics into joint spaces after orthopedic surgery. 

One paragraph of the FDA announcement particularly caught my attention:

Local anesthetics are approved as injections for the production of local or regional anesthesia or analgesia. The approved drug labels for local anesthetics do not include an indication for continuous intra-articular post-operative infusions or use of infusion devices such as elastomeric pumps. The FDA has not cleared any infusion devices with an indication for use in intra-articular infusions of local anesthetics. (emphasis mine)

This statement confirms my contention that continuous infusion via pain pumps is an off-label use of any local anesthetic.  For example, when Hospira in its label for Marcaine (Bupivacaine) makes recommendations for maximum dose volume for particular uses including local infiltration, peripheral nerve blocks, and epidurals, these same recommendations should not be considered applicable to continuous infusion because it is a categorically different use.  

The duration of anesthesia with MARCAINE is such that for most indications, a single dose is sufficient.
Maximum dosage limit must be individualized in each case after evaluating the size and physical status of the patient, as well as the usual rate of systemic absorption from a particular injection site. Most experience to date is with single doses of MARCAINE up to 225 mg with epinephrine 1:200,000 and 175 mg without epinephrine; more or less drug may be used depending on individualization
of each case.
These doses may be repeated up to once every three hours. In clinical studies to date, total daily doses have been up to 400 mg. Until further experience is gained, this dose should not be exceeded in 24 hours. (emphasis mine)

It is clear from the focus on single doses that these recommendations contemplate traditional nerve blocks and not continuous infusion.  As I understand it, most nerve blocks are performed using far less than 175 or 225 mg of Marcaine.  Moreover, the concerns regarding dosage at these volumes have been for neuro- and cardiotoxcity; in other words, systemic and not local toxicities.  Pain pumps represent a categorically different use because of the much larger volume of local anesthetics infused and the great duration of exposure the affected tissues have to the mediation —typically at least two days and as long as five days post-operatively.

Nonetheless, I-Flow's dose recommendations for its own products explicitly rely on the 400 mg total daily maximum recommendation for Marcaine as a toxic ceiling below which pain pumps allegedly may safely continuously infuse this medication.  A commonly-used 100 ml 2 ml/hr. pain pump would mean a 24-hour dose of 240 mg (24 hrs x 2 ml x 5 mg/per ml).  On what evidence are pain pump manufacturers relying that this volume of 0.5% Marcaine is safe for continuous infusion following any surgical procedure? 

Given the known toxic properties of Marcaine and other local anesthetics, in my opinion the proper standard for physicians and manufacturers should be:  what are the lowest dose, concentration, and flow rate that will produce the desired analgesic effect?  Pain pump manufacturers have a financial incentive not to frame the use of their produce in these terms, however.  Because they market their products to surgeons as a more effective alternative to oral narcotics, they are inclined to recommend the use of the most potent of the commonly-used anesthetics--Marcaine--at a high concentration--0.5%--and in large volumes.  More on these issues in my next post.  

 

 

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