Polyanalgesic Consensus Conference 2012

The need for guidance in the use of intrathecal drug administration is critical, as this is a complex and growing field of medicine. Issues include the safest and most effective methods of administering intrathecal agents based upon animal neurotoxicity data, human safety data, and the currently available efficacy data. In some instances, data helpful for creating a perfect treatment algorithm are lacking. The purpose of the Polyanalgesic Consensus Conference (PACC) is to critically evaluate currently available data, to use clinical expertise to fill the gaps in high quality evidence, and to provide guidance to health-care providers using intrathecal drug administration. The PACC is not new; the first such conference occurred in 1999 in New York. Samuel Hassenbusch, MD, PhD, and Russell Portenoy, MD, assembled a diverse group of health-care providers representing different specialties, geographic locations, and types of practice. The PACC 2000 was planned to be the first of a recurring conference that would strive to improve outcomes in both safety and efficacy. The first publication was based largely on an evaluation of the limited available literature; there was thus a great need to fill informational gaps with expert opinion. In this first PACC, morphine was the recommended first pharmacologic line of therapy, and the intrathecal use of other agents was controversial (1). Over time, some of these other agents were found to be either neurotoxic or ineffective. Four years later, it became obvious that a second conference was needed. The second conference was held and was highlighted by a change in the algorithm based on interval publications and new evidence. The major changes were the inclusion of hydromorphone as a first-line intrathecal agent and the first mention of ziconotide, which was not approved by the US Food and Drug Administration (FDA) at the time of the publication (2,3). In 2007, I was honored to be chosen to work with Drs. Hassenbusch and Krames to lead a reevaluation of intrathecal therapies in the third PACC. At that time, we also repeated a physician survey to evaluate world-wide clinical practice (4). This review of the literature, evaluation of clinical practice, and focus on clinical expertise led to the PACC 2007 publication, which changed the recommended treatment algorithm to include ziconotide as a first-line agent along the previously recommended opioids (5). During the production of this publication, the field suffered a tremendous loss with Dr. Hassenbusch’s untimely death. After a useful life of four years, and in light of significant and profound new knowledge in the field of intrathecal drug delivery, PACC 2007 became outdated. In 2011, we determined that a reevaluation of the field was appropriate. The current PACC first met in 2011 with a goal to publish these materials in 2012. This body of work chaired by myself, Robert Levy, MD, PhD, and Joshua Prager, MD, is ambitious in giving the most comprehensive and detailed guidance in the history of Intrathecal Drug Delivery Systems (IDDS). What will the reader find in this edition of Neuromodulation? The PACC 2012 includes the first separate considerations of intrathecal drug therapy for neuropathic and nociceptive pain syndromes. This is important because the literature suggests differential intrathecal drug efficacy for nociceptive versus neuropathic pain. Pharmacologic recommendations have further changed due to new evidence concerning differential drug safety and risk of granuloma formation. In the four-year hiatus between the two conferences, the associated morbidity and mortality of IDDS was highlighted in two important articles (6,7). These articles as well as an increased number of physician reported therapy related complications prompted a comprehensive evaluation of these issues and resulted in a separate PACC paper on guidance to reduce the morbidity and mortality of these therapies. The authors are hopeful that our guidance will reduce physician and staff error rates and save lives. One of the most troubling causes of patient morbidity is the development of inflammatory masses at the tips of intrathecal infusion catheters, often referred to as catheter tip granulomas. These masses are most frequently associated with high intrathecal opioid concentrations and can lead to neural injury and potentially to paraplegia. The PACC members have reexamined this important issue. Previous guidance given in two similar meetings is updated based on recent data reported to the FDA and information documented in the literature (8,9). We encourage the reader to give consideration to these important and clear-cut recommendations when clinically possible. Perhaps one of the most confusing and nonuniform issues surrounding IDDS therapy involves the proper use of trialing to determine the appropriateness of the implantation of these devices. The literature does not provide reliable comparative therapy evaluation as to the most appropriate method of trialing. The data on trialing methods have been best presented in a registry of outcomes at one year; these results were equivocal (10). In the past, several ideologic approaches to trailing have been presented each with its own benefits and drawbacks; the results of each method have been unpredictable at best. The PACC members have examined the limited data and literature to give their best guidance for trialing in 2012. At the end of the day, we believe that we have provided the best guidance possible in 2012, but one must remember that IDDS is an evolving therapy that can change rapidly with the development of a novel drug, report of an unanticipated adverse event, introduction of a new method of trialing or documentation of new drug combinations that lead to better outcomes. The keys to the future will include innovative thought, investment in science, partnership between clinicians and industry, adherence to medical ethical principles, and commitment to the S.A.F.E. (safety, appropriateness, fiscal neutrality, and efficacy) principles of algorithmic approaches to therapy (10). In closing, it is important to consider that guidelines cannot be without their flaws. The recommendations presented in this issue are based on currently available best practices and do not guarantee that complications or poor outcomes will not occur even when followed exactly as written. Health-care providers must use their clinical judgment to determine the best course of treatment for any Neuromodulation: Technology at the Neural Interface