1. Spotlight A Lot of Pain (Medications)

2. This presentation is based on the September 2014 AHRQ WebM&M Spotlight Case –See the full article at http://webmm.ahrq.govhttp://webmm.ahrq.gov –CME credit is available Commentary by: Shoshana J. Herzig, MD, MPH, Division of General Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School –Editor, AHRQ WebM&M: Robert Wachter, MD –Spotlight Editor: Bradley A. Sharpe, MD –Managing Editor: Erin Hartman, MS 2 Source and Credits

3. Objectives At the conclusion of this educational activity, participants should be able to: Appreciate the challenges of managing acute pain in hospitalized patients on chronic opioids Describe the importance of understanding the nature of the acute pain and its relationship to the chronic pain List key principles in safe prescribing of opioids in the hospital List patient-related and prescribing-related risk factors for opioid- related adverse events Describe steps to improve prescribing and monitoring of patients on opioids in the hospital Describe the Prescription Drug Monitoring Program (PDMP) and how it may improve prescribing 3

4. Case: A Lot of Pain A 58-year-old man was admitted to the hospital with a non-healing foot ulcer related to severe peripheral vascular disease. He also had a history of chronic obstructive disease and chronic pain. His pain was long-standing and related to multiple prior neck and back surgeries. For years he had been treated with long-acting morphine (extended- release 40 mg twice daily) as well as additional opioids for breakthrough pain. On admission, he reported 8/10 pain, despite receiving his home opioid regimen. After a surgical amputation to treat the ulcer, his pain worsened to 10/10. 4

5. Background Rates of opioid use, and long-term use for chronic non-cancer pain, have markedly increased over the last 2–3 decades –In one study, more than 25% of patients hospitalized at Veterans Administration Hospitals were receiving chronic opioid therapy Patients receiving chronic opioid therapy consume a disproportionate share of health care resources, including more emergency department visits and days in the hospital 5

6. Background (2) Providers frequently have to manage acute pain in hospitalized patients on chronic opioid therapy Achieving adequate pain control in patients on chronic opioid therapy is challenging –Patients may need higher doses (dependence) –Patients may experience great pain with less noxious stimuli (opioid-induced hyperalgesia) –Physicians may be reluctant to prescribe higher doses This can result in under-treatment of pain in this patient population 6

7. Evaluating the Acute Pain Understanding the nature or quality of the acute pain and its relationship to the patient's chronic pain complaint is crucial –Is acute pain related to an injury or procedure (e.g., post-operative pain after surgical amputation in this case)? –Is the chronic pain worse? Understanding the pain may allow optimal pharmacologic treatment –Inflammatory pain is optimally treated with nonsteroidal anti-inflammatory drugs (NSAIDs) –Neuropathic pain may respond well to gabapentin or pregabalin The American Society of Anesthesiologists recommends a multimodal approach to pain management, using at least 2 different classes of analgesics 7

8. Using Opioid Analgesics Once a decision is made to use opioid analgesics to manage acute post-operative pain, it is important to identify the optimal drug, dose, route, and regimen in assuring favorable risk-to-benefit ratio Guidance on these decisions comes mostly from expert opinion (see references below) Patient's previous long-acting opioid should be continued, if possible, to deliver the patient's usual baseline analgesia and avoid precipitating opioid withdrawal When adding additional opioids for acute pain, immediate- release opioids should be used to facilitate dose titration 8

9. Using Opioid Analgesics (2) Oral route is preferred to maximize duration of action If pain is severe, intravenous opioids may initially be required If possible, immediate-release opioid chosen for management of acute pain should be the same type as that used for chronic pain –Will minimize chances of adverse effects –Can facilitate ease of dose calculations 9

10. Titrating Doses of Opioid Analgesics To optimally calculate and titrate doses, it’s often easiest to convert to "oral morphine equivalents" (convert all opioids to same amount that would be given in oral morphine) Several online or handheld device calculators are available to help with this conversion If using the same type of opioid as used for the chronic pain, an initial dose of 10%–20% of baseline total daily dose should be used for acute pain This dose should be ordered on an as-needed basis (PRN), approximately every 4 hours for the oral route and every 3 hours for the intravenous route 10

11. Using a Different Opioid If necessary to change to an opioid that’s different from that used for the chronic pain, dose should be adjusted Guidelines recommend starting with a total opioid dose that is 25%–50% lower than calculated equianalgesic dose –Can avoid unintentional overdose due to incomplete cross-tolerance (i.e., patients may be more sensitive to different opioids) 11

12. Other Considerations in Choosing Other key considerations in choosing alternate opioids –Morphine and hydromorphone have fewer drug– drug interactions than other opioids –Most opioids, including morphine and hydromorphone, are mainly eliminated in the urine; may need to adjust dose in setting of renal failure 12

13. This Case The outpatient dose of 40 mg of extended-release morphine twice daily should be confirmed For his acute pain, as his chronic opioid is morphine, immediate-release morphine would be appropriate The recommended dose for the acute pain would be 10%–20% of his baseline of 80 mg/day –Morphine 8–16 mg orally every 4 hours –Adjusted based on response Give the inflammatory nature of the pain, absent contraindications, an NSAID could be added 13

14. Case: A Lot of Pain (2) In addition to post-operative surgical pain and his chronic pain, he also began having diffuse severe muscle spasms. Over the next 48 hours he was given increasing doses of extended-release morphine (up to a dose of morphine 165 mg orally three times a day), as well as intravenous and oral hydromorphone for breakthrough pain. In the afternoon on post-operative day 3, he was found to be somnolent, with an oxygen saturation of 87% on room air. His other vital signs were unremarkable and his oxygen saturation improved to 92% on 2 liters of oxygen by nasal cannula. His afternoon dose of extended-release morphine was held by the primary nurse who notified the surgical resident on duty. 14

15. Case: A Lot of Pain (3) The patient did well until 3 hours after the dose was held, when he became more alert, complained of 10/10 pain in his post-surgical leg, and had tremors and diffuse muscle spasms. The nurse treated symptoms with hydromorphone 6 mg orally and 1 mg intravenously per the prescribing orders. The surgical resident evaluated the patient and requested the extended-release morphine be given for ongoing severe pain. The nurse, reluctant to administer this medication in light of the patient's somnolence, attempted to explain this, but the resident insisted the medication be administered. Since the patient was writhing in bed with muscle spasms, the resident prescribed diazepam 5 mg intravenously (a muscle relaxant the patient had not been previously prescribed). 15

16. Case: A Lot of Pain (4) Approximately 5 minutes after diazepam was given, the patient turned pale, became minimally responsive, and was found to have a respiratory rate of 5 breaths per minute. A code blue was called for opioid and benzodiazepine overdose. The patient responded well to intravenous naloxone (an agent that acutely reverses effects of opioids) and increased oxygen by non-rebreather mask. He was transferred to the ICU for ongoing monitoring and treatment with naloxone. He was found to have new acute renal insufficiency, which likely had contributed to a build-up of opioids, enhancing their effects. He recovered well and was transferred back to the surgical unit 3 days later. He was ultimately discharged without any long-term effects. 16

17. Adverse Events With Opioids Opioids are among the top causes of drug-related adverse outcomes in hospitalized patients Opioid overdose (the most serious adverse events) may occur in 0.2%–4% of those exposed to opioids in the inpatient setting 17

18. Predictors of Opioid-Related Adverse Events Patient-related factors –Age –Obesity –Renal or hepatic failure –Sleep apnea –Chronic obstructive pulmonary disease Prescribing-related factors –High doses (in particular > 100 mg oral morphine equivalents per day) –Co-prescribing of other sedating medications 18

19. This Case This patient had several risk factors placing him at risk for an adverse events –Opioid doses in excess of 100 mg of morphine equivalents –Use of multiple opioid drugs –Co-prescription of other sedating medications (diazepam) –Renal failure 19

20. Opioid Overdose The prescribing phase of the medication-use process contributes most to opioid overdose Improper monitoring is the second most common contributor This would suggest multi-modal initiatives aimed at improving prescribing and monitoring may have the highest yield 20

21. Joint Commission Recommendations In 2012, The Joint Commission issued recommendations for safe use of opioids in hospitals For prescribing, they recommend a combination of education, use of information technology, and oversight and consultation with pain specialists 21

22. Use of Information Technology Information technology can be harnessed in a number of important ways: –Support desired prescribing practices –Build alerts for unsafe prescribing –Provide conversion support to ensure the calculation of correct doses 22

23. Pain Management Specialists/Pharmacists Consultation with pain management specialists or pharmacists is recommended when: –Converting from one opioid to another –Changing route of administration (i.e., from oral to intravenous or oral to transdermal) –Using high-risk opioids such as methadone, fentanyl, and intravenous hydromorphone Other scenarios should prompt consideration of consultation with an expert: –Uncertainty about prescribing decisions –Difficulty achieving adequate analgesia –Suspected addiction –Managing opioids in a patient with risk factor for an adverse event 23

24. Prescription Drug Monitoring Program The Prescription Drug Monitoring Program (PDMP) is an additional resource that can improve opioid prescribing by doing the following: –Assisting with outpatient opioid dose confirmation –Identification of potential addiction/misuse/diversion PDMPs are state-run databases that track all pharmacy dispensing of controlled substances Studies have shown that PDMPs can influence prescribing in primary care and the emergency department Hospitals should work toward linking PDMPs to electronic health records so the information is easily available 24

25. Monitoring Patients To improve monitoring, The Joint Commission recommends serial assessments of respiration and depth of sedation Institutions should also use pulse oximetry when indicated to monitor oxygen saturation –Should be considered when increasing the dose, changing from one opioid to another, or in patients with risk factors for adverse events –Although it should be noted that oxygen saturation can be falsely normal if patients are receiving supplemental oxygen 25

26. This Case The case illustrates many common errors in opioid prescribing for acute pain in a hospitalized patient on chronic opioids –A distinction should have been made between his chronic pain and the acute pain –Using hydromorphone instead of morphine likely contributed –Doses should have been reduced in the setting of renal failure –Benzodiazepines should generally be avoided in patients on opioids –Consultation with a pain management specialist may have prevented these prescribing errors and the adverse event 26

27. Take-Home Points Taking a thorough history regarding the nature of the pain, and differentiating acute from chronic pain, is crucial in directing optimal treatment and monitoring of response Always combine opioid and non-opioid analgesics to maximize analgesia and reduce opioid requirements. For acute pain, use immediate-release opioids to allow dose titration, preferably via the oral route, starting at a dose of approximately 10%–20% of the patient's total baseline opioid requirement. If changing to a different opioid, use a dose 25%–50% lower than the calculated equianalgesic dose Most opioids, with the exception of fentanyl, need to be dose reduced in the setting of renal failure 27

28. Take-Home Points (2) Avoid co-prescription of other medications with sedating properties—particularly benzodiazepines Consider consultation with a pain management specialist for patients at high risk of an opioid-related adverse event, or in situations of uncertainty or suspected addiction Hospitals should work toward integrating Prescription Drug Monitoring Program information into physician workflow when prescribing opioids 28