Review Article
The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines

https://doi.org/10.1111/ner.12538Get rights and content

ABSTRACT

Introduction

Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice.

Methods

The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain.

Results

The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations.

Conclusion

New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery.

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:

  • Evidence assessment

  • Pain care algorithms

  • Disease-specific indications and considerations

  • Patient-selection considerations

  • Medication-selection recommendations and considerations

  • Use context of neuropathic and nociceptive pain

  • Recommended starting dosages

  • Variables affecting chronic intrathecal therapy

  • 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

REFERENCES (289)

  • PragerJ et al.

    Best practices for intrathecal drug delivery for pain

    Neuromodulation

    (2014)
  • RauckRL et al.

    A randomized, double-blind, placebo controlled study of intrathecal ziconotide in adults with severe chronic pain

    J Pain Symptom Manage

    (2006)
  • WallaceMS et al.

    Intrathecal ziconotide in the treatment of chronic nonmalignant pain: a randomized, double-blind, placebo-controlled clinical trial

    Neuromodulation

    (2006)
  • PoreeL et al.

    Spinal cord stimulation as treatment for complex regional pain syndrome should be considered earlier than last resort therapy

    Neuromodulation

    (2013)
  • DeerTR et al.

    A definition of refractory pain to help determine suitability for device implantation

    Neuromodulation

    (2014)
  • KumarK et al.

    Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome

    Pain

    (2007)
  • HayekSM et al.

    Treatment-limiting complications of percutaneous spinal cord stimulator implants: a review of eight years of experience from an academic center database

    Neuromodulation

    (2015)
  • deVosCC et al.

    Spinal cord stimulation with hybrid lead relieves pain in low back and legs

    Neuromodulation

    (2012)
  • LindblomU et al.

    Influence on touch, vibration and cutaneous pain of dorsal column stimulation in man

    Pain

    (1975)
  • DeerTR et al.

    Polyanalgesic Consensus Conference–2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel

    Neuromodulation

    (2012)
  • DeerTR et al.

    Polyanalgesic Consensus Conference–2012: recommendations to reduce morbidity and mortality in intrathecal drug delivery in the treatment of chronic pain

    Neuromodulation

    (2012)
  • ProvenzanoDA et al.

    An international survey to understand infection control practices for spinal cord stimulation

    Neuromodulation

    (2016)
  • KohlerP et al.

    Effect of perioperative mupirocin and antiseptic body wash on infection rate and causative pathogens in patients undergoing cardiac surgery

    Am J Infect Control

    (2015)
  • BryceE et al.

    Nasal photodisinfection and chlorhexidine wipes decrease surgical site infections: a historical control study and propensity analysis

    J Hosp Infect

    (2014)
  • FarneyRJ et al.

    Sleep-disordered breathing associated with long-term opioid therapy

    Chest

    (2003)
  • YakshTL et al.

    Pharmacokinetic analysis of ziconotide (SNX-111), an intrathecal N-type calcium channel blocking analgesic, delivered by bolus and infusion in the dog

    Neuromodulation

    (2012)
  • TylerCB et al.

    Investigation of “cross-tolerance” between systemic and intrathecal morphine in rats

    Physiol Behav

    (1986)
  • KimD et al.

    Role of pretrial systemic opioid requirements intrathecal trial dose and non-psychological factors as predictors of outcome of intrathecal pump therapy: one clinician’s experience with lumbar postlaminectomy pain

    Neuromodulation

    (2011)
  • PopeJE et al.

    Advanced waveforms and frequency with spinal cord stimulation: burst and high frequency energy delivery

    Expert Rev Med Devices

    (2015)
  • Consent Decree of Permanent Injunction. United States of America vs. Medtronic, Inc., and S. Omar Ishrak and Thomas M....
  • DeerTR et al.

    Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel

    Neuromodulation

    (2012)
  • HayekSM et al.

    Intrathecal therapy for chronic pain: current trends and future needs

    Curr Pain Headache Rep

    (2014)
  • DeerTR et al.

    Factors to consider in the choice of intrathecal drug in the treatment of neuropathic pain

    Expert Rev Clin Pharmacol

    (2015)
  • SmithTJ et al.

    Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival

    J Clin Oncol

    (2002)
  • HayekSM et al.

    Age-dependent intrathecal opioid escalation in chronic noncancer pain patients

    Pain Med

    (2011)
  • DominguezE et al.

    Predictive value of intrathecal narcotic trials for long-term therapy with implantable drug administration systems in chronic non-cancer pain patients

    Pain Pract

    (2002)
  • GriderJS et al.

    Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain

    Pain Physician

    (2011)
  • HamzaM et al.

    Prospective study of 3-year follow-up of low-dose intrathecal opioids in the management of chronic nonmalignant pain

    Pain Med

    (2012)
  • BernardsCM.

    Recent insights into the pharmacokinetics of spinal opioids and the relevance to opioid selection

    Curr Opin Anaesthesiol

    (2004)
  • FrieseS et al.

    The influence of pulse and respiration on spinal cerebrospinal fluid pulsation

    Investigat Radiol

    (2004)
  • BernardsCM.

    Cerebrospinal fluid and spinal cord distribution of baclofen and bupivacaine during slow intrathecal infusion in pigs

    Anesthesiology

    (2006)
  • DoleysDM et al.

    MMPI profile as an outcome “predictor” in the treatment of noncancer pain patients utilizing intraspinal opioid therapy

    Neuromodulation

    (2001)
  • Product Surveillance Registry (PSR) Database

    (2015)
  • HayekSM et al.

    Intrathecal therapy for cancer and non-cancer pain

    Pain Physician

    (2011)
  • DeerTR et al.

    Consensus guidelines for the selection and implantation of patients with noncancer pain for intrathecal drug delivery

    Pain Physician

    (2010)
  • FalcoF et al.

    Intrathecal infusion systems for long-term management of chronic cancer pain: an update of assessment of evidence

    Pain Physician

    (2013)
  • KlothD.

    President’s Message

    NANS Newsletter

    (2015)
  • YakshTL.

    New horizons in our understanding of the spinal physiology and pharmacology of pain processing

    Semin Oncol

    (1993)
  • StaatsPS et al.

    Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial

    JAMA

    (2004)
  • PopeJE et al.

    Intrathecal therapy: the burden of being positioned as a salvage therapy

    Pain Med

    (2015)
  • Cited by (221)

    View all citing articles on Scopus

    For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http://www.wiley.com/WileyCDA/Section/id-301854.html

    [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”.]

    1

    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.

    View full text