Pain Management Interventions for Hip Fracture

1. Pain Management Interventions forHip Fracture Prepared for: Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov

2. Outline of Material • Introduction to pain management during treatment for hip fracture. • Systematic review methods. • The clinical questions addressed by the comparative effectiveness review (CER). • Results of studies and evidence-based conclusions about effectiveness and harms of pain management interventions. • Gaps in knowledge and future research needs. • What to discuss with patients and their caregivers. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

3. Health Impact in the United States ofHip Fracture From Low-Impact Injury • The incidence of hip fracture increases with age. • At age 50, the rates are 22.5 per 100,000 for men and 23.9 per 100,000 for women. • At age 80, the rates are 632.2 per 100,000 for men and 1,289.3 per 100,000 for women. • Mortality rates in the 1st year postfracture are high. • 25% for women; 37% for men. • Return to prefracture level of function is poor. • 25–50% of patients have not returned home by 1 year postfracture. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

4. Consequences of Pain From Hip Fracture • Pain following hip fracture has been associated with: • Delirium • Depression • Sleep disturbance • Altered response to treatment for comorbidities • Inadequately managed pain is associated with: • Delayed ambulation • Cardiovascular and pulmonary complications • Delayed transition to less-intensive care settings • Aggravation of comorbidities and mortality risk Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

5. Implementation of Hip FracturePain Management (1) • May be used preoperatively, intraoperatively, and postoperatively. • May be pharmacological or nonpharmacological. • May combine approaches that disrupt pain in more than one component of pain pathways. This is called “multimodal” pain management. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

6. Implementation of Hip FracturePain Management (2) • Pain management is guided by: • The prior medical status of the patient • Fracture characteristics • Requirements of the treatment plan • The patient population with pain due to hip fracture is predominantly elderly women who have significant and/or multiple comorbidities. • Over age 80: 1,289 per 100,000 women versus 632 per 100,000 men. • Comorbidities can affect both perception of pain and response to pain treatments (both benefits and harms). Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

7. Implementation of Hip FracturePain Management (3) • Usual care: Current guidelines recommend systemic analgesia, primarily with nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, as the 1st-line approach for management of moderate to severe pain in elderly patients in general. • Complications of opioids include: • Alterations in mental status • Nausea and vomiting • Respiratory depression • Tolerance • Which alternative or adjunctive methods are safe and effective options that can be used within the clinical circumstances of older adults with hip fracture? Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

8. Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development • Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, members of the public, and others. • A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment. • The results of these reviews are summarized into Clinician Guides and Consumer Guides for use in decisionmaking and in discussions with patients. The Guides and the full report, with references for included and excluded studies, are available at www.effectivehealthcare.ahrq.gov. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

9. Rating the Strength of Evidence From the CER • The strength of evidence was classified into four broad categories: Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

10. Clinical Questions Addressed by the CER (1) • In older adults, what is the effectiveness of pain management interventions for controlling acute (up to 30 days postfracture) and chronic pain (up to 1 year postfracture), compared to usual care or other interventions? • What is the effect of pain management interventions on outcomes other than pain (up to 1 year postfracture), compared to usual care or other interventions? • For example: mortality, mental status Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

11. Clinical Questions Addressed by the CER (2) • What are the nature and frequency of adverse effects associated with pain management interventions, up to 1 year postfracture? • Myocardial infarction, renal failure, and stroke • How do patient subpopulation characteristics affect effectiveness and safety? Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

12. Pain Management Interventions Includedin This CER (1) • Systemic Analgesia • Both narcotic (opioids) and non-narcotic (NSAIDs, acetaminophen) medications are typical in “usual care.” • Nerve Blocks (regional blocks) • Injection of anesthetics into nerve bundles prevents the generation and conduction of nerve impulses to the spinal cord and brain. • Traction • A traditional approach for the population of patients with hip fracture. • Preoperative skin or skeletal traction. • Goal is to stabilize the fractured leg, to reduce pain, and to improve fracture reduction. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

13. Pain Management Interventions Examined in this CER (2) • Anesthesia • Neuraxial: spinal and epidural • Injection of an anesthetic into the epidural or subarachnoid space in the spinal column • Transcutaneous Electrical Neurostimulation (TENS) • Applies electrical energy to peripheral nerves, to reduce the perception of pain • Uses varying amplitudes and frequencies, depending on indication • Rehabilitation • Part of standard postoperative care • Goal is to increase mobility and reduce pain by improving muscle strength and range of motion • Participation can be limited by delirium and degree of pain experienced by the patient Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

14. Pain Management Interventions Examined in this CER (3) • Complementary and Alternative Medicine (CAM) • Systems, practices, and products that are not part of conventional medicine, such as: • Acupressure: applying pressure at body sites away from the pain locale. • Jacobson relaxation technique: alternating between contracting and relaxing muscles. • Multimodal Pain Management • The use of multiple strategies as part of the clinical pathway. • Intent is to decrease pain to a greater extent than with one intervention alone. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

15. Clinically Significant Outcomes of Interest • Acute and Chronic Pain Intensity • Overall pain • Pain on movement • Pain at rest • Most research has focused on acute pain, the emotional and sensory response to injury, which lasts for the duration of injury and healing. • For hip fracture studies, the duration for acute pain is defined as occurring up to 30 days postfracture. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

16. Measuring Pain in Clinical Studies (1) • The patient’s self-report of pain is the standard for evaluating the character and intensity of pain. • There is no consensus about the exact cutoff for determining a clinically significant reduction in pain. • Two methods commonly used to assess the intensity of pain: • Visual analog scale (VAS): • On a 10-cm line, “where the far left is no pain and the far right end is the worst pain ever, point to how your pain feels.” • Numerical scale: • For example, “On a scale of 0–10, where 0 is no pain and 10 is the worst pain possible, how would you rate your pain?” • Numerical scales show a linear correlation with VAS results. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

17. Measuring Pain in Clinical Studies (2) • For the evidence presented here, pain measurements were evaluated as differences between intervention and comparator VAS means as measured after treatment. • Test intervention VAS mean − control intervention VAS mean = VAS mean difference. • The values are reported as centimeters (cm) difference. • For example, a mean difference of -1.0 expresses an additional 1-cm shift of the indicated point on the VAS toward “less pain,” achieved by the test intervention when compared with the control intervention. • Absolute change from baseline for test and control interventions is not reported here. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

18. Other Clinically Significant Outcomes and Adverse Events • The evidence about these outcomes and events was evaluated: • Clinically significant outcomes: • 30-day mortality rate • Mental status (delirium) • Quality of life • Serious Adverse Events: • Stroke • Myocardial infarction • Renal failure Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

19. Summary of Study Characteristics Evaluated in the Effectiveness Review: PICOTS • Population: Elderly patients experiencing pain from nonpathological, low-impact injury hip fractures. • Interventions: Pain management methods, including systemic analgesia, neuraxial anesthesia, nerve blocks, traction, TENS, rehabilitation, complementary and alternative methods, and multimodal approaches. • Comparators: usual care (non-narcotic and opioid), and/or other interventions. • Outcomes: pain intensity, mental status, 30-day mortality, serious adverse events (stroke, myocardial infarction, renal failure). • The evidence about only these key outcomes was scored for strength of evidence. • Timing: acute care, within 30 days of fracture. • Setting: acute care. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

20. Controlled Trials of Pain Interventions Examined in the Effectiveness Review Intraop = intraoperative; postop = postoperative; preop = preoperative. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

21. Controlled Trials Reporting Effectiveness for Acute Pain • Of the 71 controlled trials of pain management interventions reviewed, only 37 directly measured effects on pain. Others measured secondary outcomes (e.g., mental status). Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

22. Effectiveness of Systemic Analgesics forAcute Pain: Trials, Results, and Conclusions • No studies compared effectiveness, benefits, and harms of the systemic analgesics commonly used in pain management (non-narcotic and opioid) for elderly patients with hip fractures. • The evidence is insufficient to make any conclusions about the effectiveness or safety of these interventions or other systemic analgesics in elderly patients with hip fractures. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

23. Effectiveness of Anesthesia on Acute Pain: Trials, Results, and Conclusions • The evidence is insufficient to understand the effectiveness against acute pain of differing doses, modes of administration, and the addition of opioids to the anesthetic injection. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

24. Effectiveness of Nerve Block on Acute Pain (Overall Pain): Trials and Results Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm. *Centimeters difference; †Meta-estimate.

25. Effectiveness of Nerve Block onAcute Pain: Conclusions • In general, nerve blocks provide greater relief from the acute pain of hip fracture than usual care alone. • Strength of Evidence = Moderate • Nerve blocks used intraoperatively may be as effective as epidural and spinal anesthesia for relief of acute pain. • Strength of Evidence = Low Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

26. Effectiveness of Skin Traction on Acute Pain: Trials, Results, and Conclusions • Meta-analysis indicates that skin traction does not provide more relief from acute pain than standard care. • The difference between treated and control groups for reported intensity of pain is neither clinically important nor statistically significant. • Strength of Evidence = Low • In one trial, skeletal traction exhibited no statistically significant difference in pain relief when compared with skin traction. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

27. Effectiveness of TENS on Acute Pain: Trials, Results, and Conclusions • The meta-estimate indicates that TENS may relieve pain more than a sham control with standard care in both preoperative and postoperative use. • However, the evidence is insufficient to form a conclusion about potential benefits to assist in decisionmaking. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

28. Effectiveness of Complementary and Alternative Medicine Techniques for Acute Pain: Trials, Results, and Conclusions • Acupressure and the Jacobson relaxation technique may contribute to pain reduction over that from standard care alone, but the evidence is insufficient to permit a conclusion about the extent of potential benefits. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

29. Effectiveness of Rehabilitation on Acute Pain: Trials, Results, and Conclusions • Stretching and strengthening exercises reduced acute pain (back pain) more than standard care alone, but the evidence is insufficient to permit a conclusion about benefits. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

30. Evidence About Effectiveness for Other Outcomes • Clinically important outcomes that may show differences between pain-control methods include: • Mortality rate (at 30 days) • Mental status (delirium) • Health-related quality of life Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

31. Effectiveness of Pain Management Interventions on Other Important Outcomes • The evidence is insufficient to estimate the effect on mortality rate, mental status, or health-related quality of life of these interventions: Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

32. Effectiveness of Anesthesia on Other Important Outcomes • Continuous and single-dose modes of spinal anesthesia do not differ in effects on the 30-day mortality rate or mental status. • For all other comparisons of doses, modes of administration, and the addition of opioids to the injection, the evidence is insufficient to determine an estimate of the effect. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

33. Effectiveness of Nerve Block on Other Important Outcomes • In all studies, nerve blocks were compared with standard care alone. • Nerve blocks do not affect 30-day mortality rates. • Nerve blocks do reduce the incidence of delirium. • NNT (number needed to be treated to have one additional patient benefit, when compared with usual care,) from randomized controlled trial (RCT) data = 9. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

34. Summary of Benefits (1) • Nerve Blocks • Reduce the intensity of acute pain. • Strength of Evidence = Moderate • Can be as effective as spinal anesthesia for relief of acute pain. • Strength of Evidence = Low • Reduce the likelihood of delirium (NNT = 9). • Strength of Evidence = Moderate • Do not affect mortality rates. • Strength of Evidence = Low Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

35. Summary of Benefits (2) • Spinal Anesthesia • Continuous versus single-dose modes do not differ in effect on mortality rates or incidence of delirium. • Strength of Evidence = Low • The evidence is insufficient to understand the effectiveness and benefits of differing doses, modes of administration, and the addition of opioids to the anesthetic injection. • Skin traction • Does not reduce the intensity of acute pain. • Strength of Evidence = Low Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

36. Summary of Benefits (3) • Rehabilitation, Acupressure, Jacobson Relaxation Technique, and TENS: • The current evidence indicates that these modalities show some promise for pain relief, but the data are too limited to permit conclusions about the benefits or harms. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

37. Adverse Events Influenced by Pain Management Interventions • Evidence about clinically significant, serious adverse events influenced by pain interventions was examined for the effectiveness review. • These events are: • Stroke • Myocardial infarction • Renal failure Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

38. Studies Reporting Evidence AboutAdverse Events Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

39. Adverse Events Influenced by Pain Management Interventions • Overall, adverse event rates were similar in both treated and control groups, but studies were not powered to identify statistically significant differences. • Myocardial infarction, stroke, and renal failure were either rarely reported or no significant differences were found between groups. • The evidence is insufficient to understand the association of pain management interventions with clinically significant, serious adverse events that occur in elderly patients with hip fracture. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

40. Influence of Subpopulation Characteristics on Effectiveness and Safety (1) • Response to pain management may be affected by patient subpopulation characteristics, including: • Age • Sex • Comorbidities • Prefracture functional status Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

41. Influence of Subpopulation Characteristics on Effectiveness and Safety (2) • Only two studies of nerve blocks were performed with consideration of subpopulation characteristics. • One study in individuals with Preopexisting heart disease. • One study in individuals who were independent before their hip fracture. • No other studies were designed to determine effects of patient characteristics on outcomes. • The evidence is insufficient to understand the influences of subpopulation characteristics on effectiveness, benefits, or adverse events. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

42. Conclusions About Benefits and Adverse Events • Overall, there is limited evidence about the comparative effectiveness, benefits, and harms of pain management interventions used for elderly patients with hip fracture. • Evidence of moderate strength supports the findings that nerve blocks reduce pain and the incidence of delirium when compared with usual care alone. • Evidence of low strength supports the finding that preoperative traction does not improve relief from acute pain. • For all modalities, including those most commonly used (acetaminophen, NSAIDs, and opioids), the evidence is inadequate to estimate harms and the incidence of common adverse events in elderly patients with hip fracture. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

43. Knowledge Gaps and Future Research Needs (1) • Few studies of pain management interventions have been performed that specifically address effectiveness, benefits, and harms in elderly patients with hip fracture. • There are no studies that compare the effectiveness and safety of the systemic opioid and NSAID analgesics that are used for elderly patients with hip fracture. • There is no evidence about the effectiveness of multimodal approaches for acute pain relief, and the evidence is insufficient to understand the influence of the pain-relief approach on adverse events. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

44. Knowledge Gaps and Future Research Needs (2) • How rehabilitation techniques may affect either acute or chronic pain is unexplored. • Knowledge is very limited about the benefits and adverse events associated with pain management approaches in the long term (beyond 30 days). • Applicability of current studies is limited, as patients in institutional settings and those with cognitive impairment were rarely represented. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

45. Knowledge Gaps and Future Research Needs (3) • To improve evidence quality and reduce bias, future research should use blinded outcome assessors, validated and standardized outcome-assessment tools, adequate concealment of allocation to an intervention (where applicable), and appropriate handling of missing data. • Multicenter research studies are needed that are large enough for statistical analysis of subgroups (by age, gender, comorbidities, or prefracture functional status) and for detection of adverse effects. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.

46. What To Discuss With Your Patients and Their Caregivers • Managing pain during the period from injury through rehabilitation is important for advancing return to function and quality of life. • There are options for pain management that may be suitable for patients with a variety of comorbidities. • There is limited evidence about the benefits and harms of pain-control interventions when they are used for elderly patients with hip fractures. Abou-Setta AM, Beaupre LA, Jones CA, et al. AHRQ Comparative Effectiveness Review No. 30. Available at: http://effectivehealthcare.ahrq.gov/hippain.cfm.