Review ArticleThe Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines
Section snippets
INTRODUCTION AND RATIONALE
The use of intraspinal (intrathecal [IT]) infusion of analgesic medications to treat patients with chronic refractory pain has increased since its inception in the 1980s, and the need for clinical and outcomes research in IT therapy is ongoing. New IT devices have been recently introduced, along with novel chronic infusion strategies (1). Thus far, research has not kept pace with the growing need for innovative IT pain management, and clinical care and decision making have largely relied on
METHODS
The PACC of 2016 was designed to address the deficiencies and innovations emerging since the previous PACC of 2012 regarding IT therapy. Participants were chosen based on an executive panel from the International Neuromodulation Society (INS), with participants from previous PACC guidelines automatically nominated. Other nominations were made by board members based on a needs assessment of topics to be addressed. All participants were identified to have an area of needed expertise, which could
RECOMMENDATIONS OF PACC 2016
In this manuscript, we will explore the evidence-weighted and consensus recommendations of the PACC regarding the following topics:
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Evidence assessment
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Pain care algorithms
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Disease-specific indications and considerations
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Patient-selection considerations
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Medication-selection recommendations and considerations
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Use context of neuropathic and nociceptive pain
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Recommended starting dosages
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Variables affecting chronic intrathecal therapy
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Conclusions
EVIDENCE ASSESSMENT
It is generally regarded that IT therapy offers a reliable, accurate, safe, and efficacious treatment for both cancer and noncancer pain, as well as for end-of-life pain care. There have been multiple reviews discussing the efficacy and safety of IT therapy (26., 27., 28., 29.). Recently, IT therapy options came under scrutiny by the state of California, with success of continued access available only after a demonstration of evidence was ruled favorable (30). A more thorough understanding of
PAIN CARE ALGORITHM
Careful consideration of patient selection is foundational for successful, sustainable patient care. The fact that no recommendations were made regarding patient survival and IT therapy, or anatomic region of pain, were deficiencies of the previous 2012 PACC. Therefore, the PACC of 2016 is presenting evidence and consensus-based recommendations regarding patient survival, disease process, and medication usage for IT therapy. Attention was directed to the age of the patient, although the
DISEASE-SPECIFIC INDICATIONS AND CONSIDERATIONS
Disease-specific indications for IT therapy have been defined previously (8., 27., 56.). A conceptual marriage of many factors contribute to the implementation of the therapy once disease-specific indications have been fulfilled, including: survival time, opioid exposure/sensitivity, location of pain, type of pain, medication physiochemical properties, catheter location, pump infusion strategy, and psychological features and social support of the patient. Simply stated, IT therapy is indicated
PATIENT-SELECTION CONSIDERATIONS
Updating the PACC documents of 2012 and mindful of patient selection, managing patient comorbidities has been a concern since the IDD mortality data were reported in 2009 (41). Numerous reports have suggested best practice and careful consideration for the complex interplay between disease, patient characteristics, and drugs chosen for IT delivery. As outlined previously, consideration for all the variables and vigilance is required, and we will address them individually (8., 9., 26., 27., 56.,
MEDICATION-SELECTION RECOMMENDATIONS AND CONSIDERATIONS
Since the publication of the PACC reports of 2012, more energy by these authors has focused on patient selection, procedure standardization, and infusion therapies compared to new medications. The FDA has approved ziconotide and morphine for IT infusion for the treatment of pain. Hydromorphone from Mallinckrodt plc. is undergoing clinical trial for potential IT labeling. Notwithstanding, the PACC of 2012 provided a framework to determine which IT medications to use when differentiating the
INTRATHECAL THERAPY IN NEUROPATHIC AND NOCICEPTIVE PAIN STATES
Employing the familiar nociceptive and neuropathic pain classification for medication selection as a framework, the reorganization of medication selection is based on many factors, including survival expectation, age, previous exposure to opioids, location of pain, type of pain, and catheter location. The pharmacokinetics of the IT medications employed (112) point toward a potentially greater spread with multiple bolus delivery compared to continuous infusion.
Nociceptive and neuropathic pain,
RECOMMENDED STARTING DOSAGES
Starting dosage ranges of IT medications recommended by the PACC panel have not changed since the PACC of 2012 (Tables 20 and 21). These doses assume chronic continuous infusion. Bolus strategies have been reported (1, 116), but there are limited data to support widespread adoption. IT dosing studies with bolus-only or bolus-weighted infusion strategies are presently ongoing (35). Appropriate starting opioid dosages may vary according to the patient’s baseline oral intake at the time IT therapy
Spinal Anatomy and CSF Dynamics Relevant to IT Drug Delivery
Meninges are morphologically and physiologically implicated in mechanical, immunologic, trophic, metabolic and thermal protection of the brain and spinal cord. In relation to spinal drug delivery, the spinal meninges represent the main barrier to the transfer of drugs between the CSF and the spinal cord. Therefore, it is necessary to know if any of the meninges cause resistance or limitation to the free circulation of CSF, presenting a barrier or compartmental limitation. The spinal dural sac
Pump and Catheter Materials and Mechanics
Intrathecal pumps can be mainly differentiated into systems that are continuous flow or variable flow. The driving mechanisms may include peristalsis, fluorocarbon propellant, osmotic pressure, piezoelectric disk benders, or the combination of osmotic pressure with an oscillating piston (Table 26). Pump materials are similar with the pump shell being titanium and filling ports containing silicone rubber. Physical orientation of the filling and side ports are largely consistent, with differences
PSYCHOLOGICAL CONSIDERATIONS
The general belief that identifying comorbid psychological factors, which could compromise treatment success, was borrowed from neurostimulation practice and guidelines and applied to IT therapy, especially in the noncancer pain setting. Nelson et al. in 1996 (287) proposed a list of “red flags” to success of treatment that included suicidality, alcohol or drug dependency, unresolved compensation/legal issues, severe depression, and so on, which, although not empirically derived, made sense
EDUCATIONAL REQUIREMENTS FOR IMPLANTING AND/OR MANAGING IDDS THERAPY
The extensive scope and breadth of this sixth edition of the PACC guidelines is a reflection of the growth of knowledge related to the safe implementation of implantable IT therapies. In addition to the rapid growth of the preclinical and clinical science knowledge, there has also been an increase in the number of commercially available implantable IDDSs. While all of these devices function by pumping medication from an implantable reservoir to the IT space via an implanted catheter, their
CONCLUSIONS
The previous PACC work led to improved patient safety and efficacy and advanced questions that fostered additional IT drug research. In the same spirit, this present manuscript presents the next step in algorithmic thinking. The creation of new algorithmic tracks for neuropathic and nociceptive pain is an important step in improving patient care. The panel encourages continued research and development, including the development of new drugs, devices, and safety recommendations to improve the
Acknowledgement
The PACC was initiated by INS and funded by unrestricted educational grants from Medtronic Inc., and Jazz Pharmaceuticals, Inc. No corporate entities had any direct input into the contents of the manuscript or the conclusions of the collaborators. Sarah Staples, MA, ELS, assisted with manuscript preparation.
Authorship Statements
Dr. Deer served as primary author, project organizer and editor; Dr. Doleys, Falowski, Jacobs, Kim, and Narouze, performed literature searches; Drs. Deer, Hayek, Pope, Grider, and Erdek
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[Correction added on 19 January 2017, after first online publication: the name of the third author has been corrected from “Salim Hayek” to “Salim M. Hayek”.]
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Special comment is necessary regarding the suggested formal medical and surgical education. As this manuscript serves as a living, international document, it is clear that no uniform credentialing body exists to measure (or test) specific training criteria over such a diverse group. However, basic skill standards can be measured. Each implanter must undergo appropriate surgical tissue management training, with specific experience with implanting IT therapy. Internationally, the World Institute of Pain (WIP) created an exam to standardize internationally delivered interventional pain management, and there is discussion surrounding this effort through the educational committee collaborations of NANS, INS, and WIP. In the United States, since the inception of an American Council of Graduate Medical Education (ACGME) certified training program in Pain Medicine and surgical subspecialties of Neurosurgery or Orthopedic Spine Surgery, it is recommended that implanters have underdone and completed such training. This recommendation, does not, however, impact “legacy or grandfathered” practitioners for whom no such training was available.