Ketamine Infusions for Outpatient Pain Management

A Policy Development Project

Cheryl A. Allen, BSN, RN-BC | Ruth Conner, PhD, APRN, FNP-BC Julius R. Ivester, Jr, MD

ABSTRACT

Current literature supports using ketamine for both acute and chronic pain management. It is imperative that the development of evidence-based protocols and policies keep pace with health care delivery to ensure patient safety. This project’s objective was to formulate an outpatient ketamine infusion policy that promotes consistent and evidence-based care within a specified hospital system. This policy addresses potential side effects and minimization of adverse events by addressing patient selection, level of nursing care required, appropriate monitoring, and staff education.

Key words: chronic pain, evidence-based practice, ketamine infusion, pain, quality improvement.

Clinical Issue

Allowing pain to go untreated or undertreated has negative consequences for both the patient and the health care system, including extended hospital stays and increased hospital admissions that can lead to increased health care costs and decreased patient satisfaction.1-3 Almost 2 decades ago, Cousins et al4 recognized that health care could save between $100,000 and $1 million over the lifetime of 1 patient by preventing acute pain from becoming chronic pain. In a retrospective chart review, Coley et al1 determined that their per patient charge for unanticipated admission or readmission for postsurgical pain management was $1869. In addition, persistent or chronic pain has been estimated to cost the United States between $560 billion and $635 billion a year in treatment and lost productivity.5 Thus, health care research has long established the financial implications of undertreating or improperly treating chronic and acute pain. Recent findings suggest that ketamine hydrochloride (Ketalar; Par Pharmaceutical, Spring Valley, NY) may help prevent acute postsurgical pain from developing into difficult-to-manage chronic pain.6 Because the N-methyl-D- aspartate receptor antagonist ketamine has shown promise in conditions with difficult-to-manage pain, this older medication is now also gaining application for acute postsurgical pain.7,8 Ketamine’s use for analgesia is still considered off-label, although its utility as an analgesic is gaining acceptance. The project site had no outpatient policy on ketamine infusions for its patient population. Patients receiving ketamine infusions in an outpatient pain facility were at risk for receiving non–evidence-based care during those infusions.

Author Affiliations: Medical University of South Carolina, Charleston, South Carolina (Ms Allen, Dr Conner); Roper Hospital Ambulatory Surgery and Pain Management–James Island, Charleston, South Carolina (Ms Allen); Anesthesia Associates of Charleston PA, Charleston, South Carolina (Dr Ivester).

Problem

Medication options for chronic pain management differ from those used in acute pain management. Chronic pain conditions typically do not respond well to opioids, giving rise to nontraditional pain medications, such as ketamine, that may prevent and/or reverse central sensitization 6 and are gaining interest. 7 The project site had no policy or guiding documents for addressing patient care with ketamine infusions in the outpatient environment.

Significance

Ketamine, a realistic option for pain management, is an attractive alternative to other pain medications, such as opioids. Its attraction stems from its ability to support hemodynamic function while not suppressing respirations. In addition, ketamine has shown promise in subanesthetic intravenous doses for difficult-to-treat pain conditions, is
“safe and effective in reducing acute postoperative pain, and may help reduce opioid consumption.”

Background

Ketamine is a surgical anesthetic that may cause a dissociative state, with an altered perception of the environment and/or hallucinations. Traditionally, because of these potential psychomimetic risks, ketamine infusions were relegated to the intensive care unit. However, Schwartzman et al12 and Patil and Anitescu13 demonstrated the safe use of ketamine infusions in the outpatient environment. Because additional medications, such as propofol, benzodiazepines, and antihypertensives, may be used during subanesthetic infusions for chronic pain management, nursing care during infusion is similar to the care in a level 1 post anesthesia care unit. Because ketamine infusions have been demonstrated to be safe in the outpatient environment, health care facilities need to have a policy in place that guides patient care for this procedure.

Literature Review

Much of the literature on ketamine infusions for pain management does not distinguish inpatient from out- patient use. Common themes in the literature on the use of ketamine have included its potential to cause a dissociative state, including hallucinations and emergent reactions, as well as the potential to minimize these events by using low/subanesthetic dosing and pretreating with a benzodiazepine. Although the use of ketamine infusions for pain management raises concerns for its potential side effects, it is important to remember that most pain medications have side effects that must be taken into consideration. Ketamine’s side effects quickly resolve after the completion or discontinuation of the infusion. Potential side effects that have been reported include headache, sedation, psychomimetic issues, nausea, vomiting, and hypertension.

Schwartzman et al12 used a double-blind, placebo- controlled trial to evaluate outpatient low-dose ketamine infusions for the treatment of complex regional pain syndrome, a chronic pain condition that manifests as pain disproportionate in intensity and lasting longer than expected in consideration to the original injury. Nineteen subjects completed the study—10 in the placebo group and 9 in the ketamine group. The researchers reported that among the 19 participants, 6 complained of headache; of those, 4 were members of the group that received ketamine. The authors further reported that there were no psychomimetic events during the infusions. All participants in the study were pretreated with a benzodiazepine.

Patil and Anitescu’s13 retrospective chart review of 369 outpatient ketamine infusions in 49 patients over a 5-year period was undertaken to discern the efficacy of outpatient ketamine infusions in patients with difficult-to-manage chronic pain. Patients were pretreated with a benzodiazepine and antiemetic before the infusion. The authors noted that 23 (46.9%) patients experienced 35 adverse effects, the most common being hypertension and sedation. A literature review on acute postsurgical pain by Jouguelet- Lacoste et al8 indicated that out of 25 studies reviewed, only 1 study reported significant adverse events, which included excessive postoperative bleeding and an anaphylactic reaction to ketamine itself.

It is possible that the lack of reported significant adverse events in other studies is related to small study sizes, adequate pretreatment for anticipated side effects, proper monitoring, and patient selection.7,12-16 Although standard dosing for ketamine infusions has yet to be established— the literature indicates wide dosing ranges, which are beyond the scope of this paper to address—the likely starting dose will be conservative, then adjusted to the patient’s response. Furthermore, to mitigate ketamine’s more problematic side effects, such as nausea, psychomimetic sensations, and/or hypertension, it is feasible that other medications may be used during ketamine infusions. Side effects can be anticipated and minimized by developing patient selection criteria, providing an appropriate level of nursing care during the infusion, monitoring patients properly, developing infusion treatment protocols, and creating policies for inpatient and outpatient environments. With these elements in place, a standardized level of care in the hospital system could be offered for patients who receive ketamine infusions for pain management.

Purpose

The purpose of this quality improvement project was to develop a policy in an identified hospital system’s outpatient pain department for patients receiving ketamine infusions to treat difficult-to-manage chronic pain conditions. The policy project addressed the following: (1) patient selection criteria, (2) the level of nursing care to be provided, (3) the type/level of patient monitoring, (4) staff education, and (5) patient outcome criteria for ongoing quality improvement data.

Policy Question

Will the development and presentation of an evidence-based ketamine infusion policy by an interdisciplinary team and presentation to the chief nursing officer (CNO) and the hospital clinical practice committee result in the adoption of an outpatient ketamine infusion policy?

METHODS

Framework

Rogers’ diffusion of innovation theory, which recognizes the complex nature of change and the importance of commitment for change to be successful, was the framework of the project.17,18 Rogers’ theory is applicable because ketamine historically had negative connotations because of its psychomimetic side effects related to the large doses that typically had been used for anesthesia management. However, the side effects may be minimized in the low doses used for pain management. Because of the previously negative association with ketamine, the project leader decided that an interdisciplinary approach would help ensure that most, if not all, clinical concerns would be addressed, increasing the likelihood that the project would move forward based on clinical team consensus and commitment. Before the project start, knowledge-building interactions were used as a change tool for overcoming possible preconceived attitudes concerning ketamine’s use for analgesic purposes.

Project Design

The project began after a “preproject” period that was used for networking and informal education. At the start of the project, an interdisciplinary task force was assembled to work on policy development. Members of the team included an anesthesiologist, a nurse manager, a pharmacist, a nurse liaison to pharmacy, and the project leader. At the first meeting, the need for the project was analyzed, the protocol for policy development in the hospital system was reviewed, and a timeline was established. The project leader updated the initial literature search for any relevant studies using the same search criteria. The Cumulative Index of Nursing and Allied Health Literature, PubMed, Cochrane Database of Systematic Reviews, and National Guideline Clearinghouse were searched using the terms ketamine, ketamine infusion, safety, pain, persistent pain, chronic pain, low dose/chronic, outpatient, adverse events, practice guideline, and randomized controlled trial. Searches were limited to full-text, peer-reviewed articles, and systematic reviews, using the Boolean connector AND for different word combinations. The initial literature search yielded 336 articles. After reviewing titles and abstracts, 317 articles were discarded, leaving 19 for further, in-depth review. As a result, another 13 articles were discarded. Two additional articles were retrieved during the literature search update. Multiple drafts then were developed and reviewed by the task force, and each revision was agreed on before a change was made. Once a final version was agreed on, the policy was ready for submission to the hospital’s Policy Committee for approval.

Communication

Periodic meetings were held among the project leader, the task force, and project committee members. Various communication methods were used, including emails, phone calls, and face-to-face meetings, depending on the preferences of the task force and project committee members. Meetings had to be duplicated because not all committee members were available at the same time.

Project Timeline

The preproject phase for knowledge building and task force development took place from April to August 2016. During the fall of 2016, the official policy task force was created. Four formal meetings of 1 hour each were held. The initial meeting was held during the first week of September 2016. Subsequent meetings were held and sometimes repeated until the final meeting, which occurred in the first week of November 2016. The agenda for the initial meeting included:

  • Analysis of the need for a policy specific to the outpa- tient environment
  • Development of a timeline
  • Review of the hospital’s protocol for policy development
  • Updating the literature search for any pertinent additions

The second meeting focused on development of the initial draft document, the third focused on a review of revisions, and the fourth finalized the draft policy. The final version was submitted to the CNO for review and approval. The CNO then submitted it to the Practice Policy Committee (PPC) for consideration. It took approximately 10 weeks for a final draft to be developed, revised, and ready for submission.

Setting, Ethical Considerations, and Budget

The setting was an accredited multispecialty hospital system in the southeastern United States. Because no identifying patient data were collected and the hospital considered the research a quality improvement project, the study was exempt from institutional review board approval. There were no overt costs; however, there were hidden costs for the meetings. The hospital system absorbed the cost of staff time, and the project leader covered ancillary meeting costs.

EXPECTED OUTCOME

The expected outcome was that an interdisciplinary group could develop an evidence-based policy that reflected the concerns of each discipline represented on the task force and addressed the care of patients receiving ketamine infusions for chronic pain management in the outpatient environment. The policy was expected to gain consensus, be submitted to the appropriate committee, and gain approval.

RESULTS

A completed policy was developed by an interdisciplinary health care task force. All concerns were addressed and agreed on, and the policy (Appendix A) was submitted for the health care system CNO’s review at the end of November 2016. Additional documents were a natural out- growth from the policy development and include an admission order sheet (Appendix B) and a discharge instruction sheet (Appendix C). The policy was approved by both the CNO and the PPC in November 2016.

CONCLUSIONS

The initial reaction of the various health care disciplines that use ketamine in the outpatient environment was one of caution. This hesitation was based on the negative history of the medication as an anesthetic agent. However, by thoughtful application of Rogers’ diffusion of innovation theory and by bringing evidence-based literature to the task force, all parties were soon able to become familiar and comfortable with how the use of this treatment modality in the outpatient environment might benefit a specific patient population. An interdisciplinary approach to clinical policy development allowed each discipline’s concerns to be addressed rapidly, with the primary interest being the safety of patients. The policy was developed based on evidence-based literature, and it addressed the concerns of all task force members regarding patient safety, patient selection, appropriate monitoring during infusion therapy, staff education, and appropriate staffing. The interdisciplinary task force was able to reach consensus quickly on a clinical policy and gain the approval of both the CNO and the PPC.

In today’s world of fast-paced health care change, using an interdisciplinary group for clinical needs allows for most, if not all, clinical concerns to be addressed in a timely manner. When considering patients with chronic pain conditions, treatment in the outpatient environment offers many benefits, including lower treatment costs. In addition, the patient usually sees the same clinical staff. Under these circumstances, a therapeutic relationship may develop that allows a holistic approach to pain care. This project was specific to the health care system in which it took place, and it is recognized that it may not be applicable to other institutions. However, it is hoped that other facilities treating patients with chronic pain conditions will consider researching if and how outpatient ketamine infusions might be provided in their own system.

ACKNOWLEDGMENTS

The authors would like to thank members of the project task force: Carin Hosler, BSN, RN, Roper Hospital pharmacy nurse liaison; John Fowler, PharmD, BCPS, Roper Hospital pharmacy manager; Stacey Daffin, BSN, RN, staff nurse at the project site; Robyn Getsinger, BSN, RN, clinical manager at the project site; Debbie Liafsha, BSN, RN, and Barbara Evans, RT, staff at the project site; and Carolyn Donohue, MSN, RN, NE-BC, chief nursing officer for Roper Hospital and project mentor. They also thank Tom Smith, PhD, and John Dinolfo, PhD, at the Center for Academic Excellence of the Medical University of South Carolina, and Margaret E. Allen, freelance copy editor, for their help in the preparation of this manuscript.

REFERENCES

  • Coley KC, Williams BA, DaPos SV, Chen C, Smith RB. Retrospective evaluation of unanticipated admissions and readmissions after same day surgery and associated costs. J Clin Anesth. 2002;14(5):349-353.
  • Joshi GP, Beck DE, Emerson RH, et al. Defining new directions for more effective management of surgical pain in the United States: highlights of the inaugural Surgical Pain Congress. Am Surg. 2014;80(3):219-228.
  • Keller DS, Smalarz A, Haas EM. Developing a tool to measure pharma- coeconomic outcomes of post-surgical pain management interven- tions. J Med Econ. 2016;19(1):91-100.
  • Cousins MJ, Power I, Smith G. 1996 Labat lecture: pain—a persistent problem. Reg Anesth Pain Med. 2000;25(1):6-21.
  • Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13(8):715-724.
  • McNicol ED, Schumann R, Haroutounian S. A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain. Acta Anaesthesiol Scand. 2014;58(10):1199-1213.
  • Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77(2):357-367.
  • Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly JE. The use of intravenous infusion or single dose of low-dose ketamine for post- operative analgesia: a review of the current literature. Pain Med. 2015;16(2):383-403.
  • Ahern TL, Herring AA, Miller S, Frazee BW. Low-dose ketamine infu- sion for emergency department patients with severe pain. Pain Med. 2015;16(7):1402-1409.
  • Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016;17(2):131-157.
  • Strayer RJ, Nelson LS. Adverse events associated with ketamine for procedural sedation in adults. Am J Emerg Med. 2008;26(9):985-1028.
  • Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009;147(1-3):107-115.
  • Patil S, Anitescu M. Efficacy of outpatient ketamine infusions in refrac- tory chronic pain syndromes: a 5-year retrospective analysis. Pain Med. 2012;13(2):263-269.
  • Azari P, Lindsay DR, Briones D, Clarke C, Buchheit T, Pyati S. Efficacy and safety of ketamine in patients with complex regional pain syn- drome: a systematic review. CNS Drugs. 2012;26(3):215-228.
  • O’Connell NE, Wand BM, McAuley J, Marston L, Moseley GL. Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013;(4):CD009416. doi: 10.1002/14651858.CD009416.pub2.
  • Sigtermans M, van Hilten J, Bauer M, et al. Ketamine produces effec- tive and long-term pain relief in patients with complex regional pain syndrome type 1. Pain. 2009;145(3):304-311.
  • Rogers EM. Diffusion of Innovations. 5th ed. New York, NY: Free Press; 2003.
  • Finkelman A. Leadership and Management for Nurses: Core Competencies for Quality Care. 2nd ed. Upper Saddle River, NJ: Pearson; 2012.