Inpatient pain management in sickle cell disease

Inpatient pain management in sickle cell disease Abstract Purpose A novel strategy for management of acute pain associated with sickle cell disease (SCD), referred to as the oral tier approach, is described. Summary SCD is an inherited blood disorder characterized by episodic acute pain known as vaso-occlusive crisis (VOC), which is the most common reason for emergency department visits and hospital admissions in patients with SCD; these patients are often treated with parenteral opioids on admission and then transitioned to oral opioids prior to discharge. In this report, experience with use of the oral tier approach in 3 patients with SCD hospitalized for management of VOC is reported. As per usual practice, acute pain was initially managed with parenteral opioids via patient-controlled analgesia (PCA). Once pain control was established, an oral tier was added. The oral tier consisted of 3 orders. The first order was for an oral opioid, to be administered every 3 hours on a scheduled basis; however, the patient could refuse 1 or more of these scheduled doses. Two additional orders specified that the patients could receive additional oral opioids in incremental doses for moderate (grade 4–7) or severe (grade 8–10) pain if appropriate. To facilitate transition to an oral regimen with which the patients might be discharged, they were encouraged to use oral opioids in preference to parenteral opioids. Opioid usage and average daily pain scores for the 3 patients are reported. Conclusion Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC. analgesics, anemia, opioid, pain/drug therapy, pain measurement, sickle cell/drug therapy KEY POINTS The oral tier is a flexible, simple, and safe approach that has been successfully used to facilitate the transition from a parenteral to an oral pain regimen in inpatients with acute sickle cell pain crisis. This strategy allows patients to control inpatient opioid dosing within safe limits and allows providers to more rapidly identify an effective discharge opioid dosing regimen. Healthcare professionals can recommend this novel approach in order to promote patient satisfaction and shorter lengths of stay. Sickle cell disease (SCD) is a group of inherited blood disorders that affect approximately 100,000 Americans.1 Patients with SCD express a variation of normal adult hemoglobin referred to as hemoglobin S (HbS). In the homozygous variant of SCD (the HbSS genotype), which is the most common type of SCD and sometimes referred to as sickle cell anemia, both globin alleles are S mutants.2,3 As people living with SCD age, most will experience the onset of chronic, virtually daily pain, which is punctuated by episodes of acute pain.3 Acute episodic pain, known as vaso-occlusive crisis (VOC), is the hallmark symptom of SCD.4–6 Patients suffering from VOC often visit the emergency department (ED) for pain relief. The standard of care is appropriate hydration and pain management with repeated doses of parenteral opioids, other analgesics, and nonpharmacologic measures.2,3 If adequate pain control cannot be achieved in an infusion center or ED with repeated boluses of parenteral opioids, patients are admitted for pain management until the sickling process abates.4 Appropriately treating acute pain may improve quality of life and decrease length of stay and readmission rates.7–9 In the case series presented here, we describe a novel opioid management strategy referred to as the oral tier. The oral tier is a flexible, simple, and safe approach that facilitates the transition from parenteral to oral opioids. Background When admitted to our institution, patients are switched from repeated i.v. opioid boluses to automated patient-controlled analgesia (PCA). Typically, PCA with either hydromorphone or morphine is used due to those drugs’ favorable pharmacokinetic profiles.10,11 The PCA device is programmed to deliver a demand dose, which is determined by experience from prior admissions or calculations based upon the patient’s outpatient opioid usage. The PCA device is also programmed with a minimum demand dose (“lockout”) interval of 10 minutes. The basal infusion feature is rarely used, because long-acting opioids are typically continued on an outpatient basis. Similarly, the “bolus as needed” feature is seldom used. The amount of opioid necessary to control acute pain may vary considerably among patients, depending upon the nature of the pain and the common phenomenon of native or acquired opioid tolerance.12 Most established patients have individualized pain treatment plans, which are created by the patient’s hematologist and are available in the electronic medical record to guide ED and admitting providers. Multiple techniques are used to assess the degree of pain control. For inadequate pain control, the PCA demand dose is increased by 50–100%. If the patient experiences unacceptable adverse effects, especially excessive sedation or respiratory depression, the dose is typically decreased considerably or the lockout interval is increased. The following guidelines are used to assess the appropriateness of PCA orders: (1) If the delivered dose rate is less than 1 dose per hour, the dose may be too high, and the patient may be at risk for excessive sedation or respiratory depression; (2) if the delivered dose rate is more than 2 doses per hour, the patient may benefit from a higher dose to prevent the need for frequent dosing attempts, which may contribute to uninterrupted sleep. We think a delivered dose rate of 1–2 doses per hour is optimal. At least every 4 hours, nursing staff assess vital signs, including respiratory rate; level of consciousness; and pain scores, as determined using a numerical rating scale on which the patient self-reports pain on a scale of 0 to 10, with 0 indicating no pain and 10 indicating severe pain.13 Lastly, pain control is subjectively assessed by asking patients if they are receiving enough pain medications. When pain has been adequately controlled with PCA, an oral tier is added. Selection of the most appropriate oral agent can be influenced by insurance coverage, drug shortages, physician preferences, and opioid diversion risk. Current guidelines recommend a switch from parenteral to oral opioids based upon a calculation of equianalgesic doses.14 The standard approach to calculate a safe and effective oral opioid regimen typically involves 4 steps15,16: For each type of opioid administered over the past 24 hours, capture the name, route of administration, and total amount administered. Select a short-acting oral opioid for inpatient use, typically one that will be continued on an outpatient basis at discharge. Using appropriate conversion factors, convert the total amount of opioid administered in 24 hours to an equivalent amount of the selected short-acting opioid. If the previously used parenteral agent differs from the selected short-acting opioid agent (for example, with conversion from i.v. morphine to oral oxycodone), consider reducing the total opioid equivalent by 25–50% to account for incomplete cross-tolerance. If indicated, divide the total daily opioid amount into approximately equal amounts of short- and long-acting medications. This standard approach is commonly implemented with as-needed inpatient orders. We see 3 problems with this approach. First, activation of an as-needed order requires that the patient get the attention of the nurse, usually by pressing a bedside button; this results in delays that are painful and frustrating to the patient. Second, as-needed orders specify a single dose amount, whereas patients need varying amounts of opioid to control their varying pain. Third, as-needed orders typically are written with time intervals that exceed the expected duration of effect of an oral opioid dose. The oral tier is intended to address these problems and facilitate rapid discharge. It should be noted that with this approach patients are not switched from PCA to oral opioids; rather, PCA is continued and an oral tier added. This approach allows a smooth transition, and we have found it to be safe for patients. The oral tier consists of 3 opioid orders. The opioid agent chosen for the oral tier is typically the patient’s outpatient short-acting opioid. The dosing can be based on expected need (according to calculations described above) or doses similar to what the patient had been using on an outpatient basis. The first order specifies an amount of an opioid to be administered on a scheduled basis every 3 hours, with the stipulation that the patient may refuse. The order might read, “morphine 30 mg orally every 3 hours (scheduled), patient may refuse.” This order helps to ensure that the nurse will be at the bedside every 3 hours, at which time points the patient will undergo a pain assessment and participate in a decision about oral dosing. It eliminates the delays and frustrations intrinsic to as-needed dosing. The second and third orders specify additional amounts of opioid to be administered on an as-needed basis for moderate or severe pain at the same time as the scheduled dose. These orders might read, “morphine 15 mg orally every 3 hours p.r.n. for moderate (pain score 4–7) pain OR morphine 30 mg orally every 3 hours p.r.n. for severe (pain score 8–10) pain.” Nurses may withhold the oral opioids for contraindications such as excessive sedation or respiratory depression. Based on this example, a patient may receive 0, 15, 30, or 45 mg of oral morphine every 3 hours. The benefit of this approach is that we are able to quickly decrease the dosage of the PCA while simultaneously identifying an oral regimen that is safe for discharge. Once the oral tier is initiated, patients are encouraged to use the oral tier in preference to PCA. With the addition of the oral tier, a PCA-delivered dose rate of less than 1 dose per hour is no longer considered a marker of a possibly too-high dose, as the delivered dose rate is expected to gradually approach 0 as patients take more of the oral medication. Many patients are able to transition to an oral opioid exclusively over a few days without any change in PCA device settings. Other patients are not able to make this transition by choice, in which case the lockout interval is incrementally increased (e.g., from 10–20 to 30–60 minutes) over 2 or 3 days. Once this transition has occurred and acute pain has either subsided or is controlled with the oral tier, both patients and providers can recognize that discharge is appropriate. The discharge regimen may be expected to remain stable or to be tapered over time. The 3 cases below describe the successful use of the oral tier. In these cases, the mean pain score is the daily mean of all 3-hour patient-reported pain scores. Additionally, total parenteral opioid is reported as milligrams per hour, as opposed to total daily dose, since patients are admitted for less than a full 24 hours on days of admission or discharge; this allows for a more accurate depiction of changes in opioid utilization throughout the hospital stay. Although we describe only 3 cases, our experience indicates that our approach is safe. Over the past 6 years we have had an average daily census of approximately 4 patients, the vast majority of whom were treated in the manner described here. Case summary 1 A 20-year-old man with chronic pain secondary to SCD (HbSS genotype) had an outpatient opioid regimen of morphine sulfate extended release (ER) 15 mg tablets, 1 tablet every 12 hours; and hydromorphone hydrochloride 8 mg tablets, 1–3 tablets every 3 hours as needed for breakthrough pain (prescribed quantity, 42 tablets for 7 days). The patient had been made aware that he was limited to an average of 6 hydromorphone tablets per day; within this limit, he could use the hydromorphone as needed for pain. His pain management regimen also included gabapentin 900 mg twice daily. On day 1 (see Figure 1 and Table 1), the patient presented to the ED and was subsequently admitted for management of VOC involving the lower-extremity joints and back. He received a total of 16 mg of i.v. morphine sulfate in the ED. His home medications (morphine sulfate ER 15 mg every 12 hours and gabapentin 300 mg 3 times daily) were continued during the admission. Intravenous hydromorphone PCA was initiated with a demand dose of 0.4 mg and a lockout interval of 10 minutes. These PCA settings were unchanged from day 1 to day 3 of his hospital stay. He also received i.v. ketorolac tromethamine 30 mg every 6 hours on days 1 through 3. At the end of day 1, including time spent in the ED, he received a total of 17.2 mg of i.v. hydromorphone hydrochloride equivalents from both PCA and i.v. bolus doses. The delivered PCA dose rate was 2.2 doses per hour. His average pain score was 7.3. Figure 1. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 1. Total parenteral hydromorphone use is reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. Total oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Figure 1. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 1. Total parenteral hydromorphone use is reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. Total oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Table 1. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 1 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 aTotal parenteral hydromorphone reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. bTotal oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Open in new tab Table 1. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 1 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 aTotal parenteral hydromorphone reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. bTotal oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Open in new tab On day 2, an oral tier was initiated with hydromorphone hydrochloride 8 mg by mouth every 3 hours (scheduled) and hydromorphone hydrochloride 8 mg every 3 hours as needed for moderate pain or hydromorphone hydrochloride 16 mg every 3 hours as needed for severe pain. He received 56.8 mg of i.v. hydromorphone hydrochloride, with a delivered dose rate of 6.5 doses per hour, and 96 mg of oral hydromorphone hydrochloride. His average pain score was 4.4. On day 3 the patient’s PCA was discontinued after he had received 13.6 mg of i.v. hydromorphone hydrochloride, with a delivered dose rate of 0.9 doses per hour. He received a total of 192 mg of oral hydromorphone hydrochloride. His average pain score was 5.4. On day 4, he received 96 mg of oral hydromorphone hydrochloride prior to discharge. He was discharged on his previous home opioid regimen. His average pain score was 5.8, which he considered acceptable. The patient attended a follow-up appointment at his outpatient clinic within 2 weeks of discharge. Case summary 2 A 30-year-old woman with chronic pain due to SCD (HbSS genotype) had an outpatient opioid regimen of transdermal fentanyl 75 µg/hr, oxycodone hydrochloride immediate release (IR) 10 mg tablets, 1–2 tablets every 3 hours as needed for mild or moderate pain (prescribed quantity, 100 tablets for 3 weeks); and morphine sulfate IR 30 mg tablets, 1–3 tablets every 3 hours as needed for severe pain (prescribed quantity, 40 tablets for 3 weeks). It should be noted that a regimen involving 2 short-acting opioids is very unusual at our practice site. The patient’s outpatient pain management regimen also included ibuprofen 400 mg tablets, up to 4 tablets daily as needed for pain, and transdermal lidocaine. On day 1 (see Figure 2 and Table 2) the woman presented to the ED of a nearby hospital with VOC involving both shoulders, the neck, and both wrists. The pain was refractory to ED management, including 32 mg of i.v. morphine sulfate administered over a period of 6 hours. That day she was transferred to our institution’s inpatient service, where she received a single dose of subcutaneous morphine sulfate 2 mg and was started on i.v. morphine sulfate PCA with a demand dose of 2 mg and a lockout interval of 10 minutes. Her home medications (transdermal fentanyl, transdermal lidocaine, and ibuprofen) were continued. She did not receive any doses from her PCA device, and the average pain score was 6. Figure 2. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 2. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Figure 2. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 2. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Table 2. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 2 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab Table 2. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 2 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab On day 2, the PCA lockout interval was extended to 30 minutes. An oral tier was initiated with oxycodone hydrochloride IR 10 mg every 3 hours (scheduled) and oxycodone hydrochloride IR 10 mg every 3 hours as needed for moderate pain or oxycodone hydrochloride IR 20 mg every 3 hours p.r.n. for severe pain. She received a total of 76.8 mg of i.v. morphine sulfate, with a delivered dose rate of 1.6 doses per hour, and 10 mg of oxycodone hydrochloride IR. Her average pain score was 5. On day 3, the PCA lockout interval was extended to 60 minutes. The patient received a total of 20 mg of i.v. morphine sulfate, with a delivered dose rate of 0.4 doses per hour, and 60 mg of oxycodone hydrochloride IR. Her average pain score was 4.5. On day 4, PCA was discontinued, and the patient received 20 mg of oxycodone prior to discharge. She was discharged on her previous home opioid regimen. Her average pain score was 4.5, which she considered acceptable. The patient attended a follow-up appointment at her outpatient clinic within 2 weeks of discharge. Case summary 3 A 30-year-old woman with chronic pain due to SCD (HbSS genotype) had an outpatient opioid regimen of morphine sulfate ER 30 mg every 12 hours and oxycodone hydrochloride IR 30 mg tablets, 1–3 tablets every 3 hours as needed for breakthrough pain (prescribed quantity, 70 tablets for 7 days). She presented to our institution’s infusion center with a significant increase in lower extremity and lower back pain. On day 1 (See Figure 3 and Table 3) the patient received 45 mg of i.v. morphine sulfate in the infusion center, with inadequate pain relief, and was admitted. Intravenous morphine sulfate PCA was initiated with a demand dose of 4 mg and a lockout interval of 10 minutes. Morphine sulfate ER 30 mg orally every 12 hours was continued, and an oral tier was initiated with oxycodone hydrochloride IR 30 mg every 3 hours (scheduled) and oxycodone hydrochloride IR 30 mg orally every 3 hours as needed for moderate pain or oxycodone hydrochloride IR 60 mg orally every 3 hours as needed for severe pain. She received a total of 52 mg of i.v. morphine sulfate via PCA, with a delivered dose rate of 1.4 doses per hour, and 30 mg of oxycodone hydrochloride IR. She was also started on i.v. ketorolac tromethamine 30 mg every 6 hours (scheduled). Her average pain score was 6.9. Figure 3. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 3. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Figure 3. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 3. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Table 3. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab Table 3. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab On day 2, the PCA lockout interval was increased to 20 minutes. She received a total of 80 mg of i.v. morphine sulfate, with a delivered dose rate of 0.9 per hour, and 120 mg of oxycodone hydrochloride IR. Her average pain score was 6.75. On day 3, the PCA lockout interval was increased to 60 minutes. The patient received a total of 44 mg of i.v. morphine sulfate, with a delivered dose rate of 0.5 dose per hour, and 180 mg of oxycodone hydrochloride IR. Her average pain score was 7.11. On day 4, PCA was discontinued, and the patient received 90 mg of oxycodone hydrochloride IR prior to discharge. She was discharged on her previous home regimen. Her average pain score was 6.33, which she considered acceptable. The patient did not arrive for a scheduled outpatient clinic appointment and was subsequently readmitted the following week for treatment of medical problems unrelated to sickle cell crisis. Discussion The dynamic nature of acute pain in SCD is apparent in these 3 case summaries. In all 3 patients, the amount of opioid needed per hour to provide acceptable pain relief decreased dramatically over 4 days. The flexibility of the combination of PCA and an oral tier allowed patients to decrease their use of PCA and increase their use of the oral tier simultaneously while maintaining adequate pain control; it facilitated a rapid transition to an oral regimen appropriate for discharge. The willingness of patients to be discharged with pain scores greater than 4 exemplifies the accommodation of this patient population to higher pain scores as long as they have access to home opioids that they can use in a flexible manner. A limitation of this case series was the small sample size and the lack of a true comparator group. Because of this, we were unable to assess additional factors, such as whether transitioning to the oral tier made an impact on length of stay or reduced medication errors. Each of these patients and their individual opioid requirements were well known to the service providers involved. They had been previously admitted and initiated on an oral tier in the past. In implementing the oral tier approach, we have used very little naloxone to reverse suspected opioid overdose, and there have been no deaths attributed to opioid overdose. The issue of whether the success of the oral tier has contributed to our low usage of naloxone has not yet been assessed. A more robust study must be conducted to make this assessment. Conclusion Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC. Disclosures The authors have declared no potential conflicts of interest. References 1. Centers for Disease Control and Prevention . What is sickle cell disease? (revised August 2017). https://www.cdc.gov/ncbddd/sicklecell/facts.html ( accessed 2018 Aug 22 ). 2. Howard J , Telfer P. Sickle cell disease in clinical practice . London : Springer ; 2015 : 3 - 70 . Google Preview WorldCat COPAC 3. Yawn BP , Buchanan GR , Afenyi-Annan AN et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members . JAMA. 2014 ; 312 ( 10 ): 1033 - 48 . Google Scholar Crossref Search ADS PubMed WorldCat 4. National Heart, Lung, and Blood Institute . The management of sickle cell disease . Bethesda, MD : National Institutes of Health ; revised 2002 Jun. NIH publication no. 02-2117. WorldCat COPAC 5. Manwani D , Frenette PS . Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies . Blood. 2013 ; 122 ( 24 ): 3892 - 8 . Google Scholar Crossref Search ADS PubMed WorldCat 6. Payne R . Pain management in sickle cell disease . Ann N Y Acad Sci. 1989 ; 565 : 189 - 206 . Google Scholar Crossref Search ADS PubMed WorldCat 7. Strassels S , Mcnicol E , Wagner A et al. Persistent postoperative pain, health-related quality of life, and functioning 1 month after hospital discharge . Acute Pain. 2004 ; 6 ( 3 ): 95 - 104 . Google Scholar Crossref Search ADS WorldCat 8. Coley KC , Williams BA , DaPos SV et al. Retrospective evaluation of unanticipated admissions and readmissions after same day surgery and associated costs . J Clin Anesth. 2002 ; 14 ( 5 ): 349 - 53 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Morrison RS , Magaziner J , McLaughlin MA et al. The impact of post-operative pain on outcomes following hip fracture . Pain. 2003 ; 103 ( 3 ): 303 - 11 . Google Scholar Crossref Search ADS PubMed WorldCat 10. Morphine sulfate package insert . Lake Forest, IL : Hospira, Inc. ; 1984 (revised 2011 Nov). WorldCat COPAC 11. Dilaudid (hydromorphone) package insert . Stamford, CT : Purdue Pharma L.P. ; 1984 Jan (revised 2016 Dec). WorldCat COPAC 12. Dumas EO , Pollack GM . Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective . AAPS J. 2008 ; 10 ( 4 ): 537 - 51 . Google Scholar Crossref Search ADS PubMed WorldCat 13. Bijur PE , Latimer CT , Gallagher EJ . Validation of a verbally administered numerical rating scale of acute pain for use in the emergency department . Acad Emerg Med. 2003 ; 10 ( 4 ): 390 - 2 . Google Scholar Crossref Search ADS PubMed WorldCat 14. Chou R , Fanciullo GJ , Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain . J Pain. 2009 ; 10 ( 2 ): 113 - 30 . Google Scholar Crossref Search ADS PubMed WorldCat 15. Pereira J , Lawlor P , Vigano A et al. Equianalgesic dose ratios for opioids. A critical review and proposals for long-term dosing . J Pain Symptom Manage. 2001 ; 22 ( 2 ): 672 - 87 . Google Scholar Crossref Search ADS PubMed WorldCat 16. Derby S , Chin J , Portenoy RK . Systemic opioid therapy for chronic cancer pain . CNS Drugs. 1998 ; 9 ( 2 ): 99 - 109 . Google Scholar Crossref Search ADS WorldCat © American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Health-System Pharmacy Oxford University Press

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Abstract

Abstract Purpose A novel strategy for management of acute pain associated with sickle cell disease (SCD), referred to as the oral tier approach, is described. Summary SCD is an inherited blood disorder characterized by episodic acute pain known as vaso-occlusive crisis (VOC), which is the most common reason for emergency department visits and hospital admissions in patients with SCD; these patients are often treated with parenteral opioids on admission and then transitioned to oral opioids prior to discharge. In this report, experience with use of the oral tier approach in 3 patients with SCD hospitalized for management of VOC is reported. As per usual practice, acute pain was initially managed with parenteral opioids via patient-controlled analgesia (PCA). Once pain control was established, an oral tier was added. The oral tier consisted of 3 orders. The first order was for an oral opioid, to be administered every 3 hours on a scheduled basis; however, the patient could refuse 1 or more of these scheduled doses. Two additional orders specified that the patients could receive additional oral opioids in incremental doses for moderate (grade 4–7) or severe (grade 8–10) pain if appropriate. To facilitate transition to an oral regimen with which the patients might be discharged, they were encouraged to use oral opioids in preference to parenteral opioids. Opioid usage and average daily pain scores for the 3 patients are reported. Conclusion Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC. analgesics, anemia, opioid, pain/drug therapy, pain measurement, sickle cell/drug therapy KEY POINTS The oral tier is a flexible, simple, and safe approach that has been successfully used to facilitate the transition from a parenteral to an oral pain regimen in inpatients with acute sickle cell pain crisis. This strategy allows patients to control inpatient opioid dosing within safe limits and allows providers to more rapidly identify an effective discharge opioid dosing regimen. Healthcare professionals can recommend this novel approach in order to promote patient satisfaction and shorter lengths of stay. Sickle cell disease (SCD) is a group of inherited blood disorders that affect approximately 100,000 Americans.1 Patients with SCD express a variation of normal adult hemoglobin referred to as hemoglobin S (HbS). In the homozygous variant of SCD (the HbSS genotype), which is the most common type of SCD and sometimes referred to as sickle cell anemia, both globin alleles are S mutants.2,3 As people living with SCD age, most will experience the onset of chronic, virtually daily pain, which is punctuated by episodes of acute pain.3 Acute episodic pain, known as vaso-occlusive crisis (VOC), is the hallmark symptom of SCD.4–6 Patients suffering from VOC often visit the emergency department (ED) for pain relief. The standard of care is appropriate hydration and pain management with repeated doses of parenteral opioids, other analgesics, and nonpharmacologic measures.2,3 If adequate pain control cannot be achieved in an infusion center or ED with repeated boluses of parenteral opioids, patients are admitted for pain management until the sickling process abates.4 Appropriately treating acute pain may improve quality of life and decrease length of stay and readmission rates.7–9 In the case series presented here, we describe a novel opioid management strategy referred to as the oral tier. The oral tier is a flexible, simple, and safe approach that facilitates the transition from parenteral to oral opioids. Background When admitted to our institution, patients are switched from repeated i.v. opioid boluses to automated patient-controlled analgesia (PCA). Typically, PCA with either hydromorphone or morphine is used due to those drugs’ favorable pharmacokinetic profiles.10,11 The PCA device is programmed to deliver a demand dose, which is determined by experience from prior admissions or calculations based upon the patient’s outpatient opioid usage. The PCA device is also programmed with a minimum demand dose (“lockout”) interval of 10 minutes. The basal infusion feature is rarely used, because long-acting opioids are typically continued on an outpatient basis. Similarly, the “bolus as needed” feature is seldom used. The amount of opioid necessary to control acute pain may vary considerably among patients, depending upon the nature of the pain and the common phenomenon of native or acquired opioid tolerance.12 Most established patients have individualized pain treatment plans, which are created by the patient’s hematologist and are available in the electronic medical record to guide ED and admitting providers. Multiple techniques are used to assess the degree of pain control. For inadequate pain control, the PCA demand dose is increased by 50–100%. If the patient experiences unacceptable adverse effects, especially excessive sedation or respiratory depression, the dose is typically decreased considerably or the lockout interval is increased. The following guidelines are used to assess the appropriateness of PCA orders: (1) If the delivered dose rate is less than 1 dose per hour, the dose may be too high, and the patient may be at risk for excessive sedation or respiratory depression; (2) if the delivered dose rate is more than 2 doses per hour, the patient may benefit from a higher dose to prevent the need for frequent dosing attempts, which may contribute to uninterrupted sleep. We think a delivered dose rate of 1–2 doses per hour is optimal. At least every 4 hours, nursing staff assess vital signs, including respiratory rate; level of consciousness; and pain scores, as determined using a numerical rating scale on which the patient self-reports pain on a scale of 0 to 10, with 0 indicating no pain and 10 indicating severe pain.13 Lastly, pain control is subjectively assessed by asking patients if they are receiving enough pain medications. When pain has been adequately controlled with PCA, an oral tier is added. Selection of the most appropriate oral agent can be influenced by insurance coverage, drug shortages, physician preferences, and opioid diversion risk. Current guidelines recommend a switch from parenteral to oral opioids based upon a calculation of equianalgesic doses.14 The standard approach to calculate a safe and effective oral opioid regimen typically involves 4 steps15,16: For each type of opioid administered over the past 24 hours, capture the name, route of administration, and total amount administered. Select a short-acting oral opioid for inpatient use, typically one that will be continued on an outpatient basis at discharge. Using appropriate conversion factors, convert the total amount of opioid administered in 24 hours to an equivalent amount of the selected short-acting opioid. If the previously used parenteral agent differs from the selected short-acting opioid agent (for example, with conversion from i.v. morphine to oral oxycodone), consider reducing the total opioid equivalent by 25–50% to account for incomplete cross-tolerance. If indicated, divide the total daily opioid amount into approximately equal amounts of short- and long-acting medications. This standard approach is commonly implemented with as-needed inpatient orders. We see 3 problems with this approach. First, activation of an as-needed order requires that the patient get the attention of the nurse, usually by pressing a bedside button; this results in delays that are painful and frustrating to the patient. Second, as-needed orders specify a single dose amount, whereas patients need varying amounts of opioid to control their varying pain. Third, as-needed orders typically are written with time intervals that exceed the expected duration of effect of an oral opioid dose. The oral tier is intended to address these problems and facilitate rapid discharge. It should be noted that with this approach patients are not switched from PCA to oral opioids; rather, PCA is continued and an oral tier added. This approach allows a smooth transition, and we have found it to be safe for patients. The oral tier consists of 3 opioid orders. The opioid agent chosen for the oral tier is typically the patient’s outpatient short-acting opioid. The dosing can be based on expected need (according to calculations described above) or doses similar to what the patient had been using on an outpatient basis. The first order specifies an amount of an opioid to be administered on a scheduled basis every 3 hours, with the stipulation that the patient may refuse. The order might read, “morphine 30 mg orally every 3 hours (scheduled), patient may refuse.” This order helps to ensure that the nurse will be at the bedside every 3 hours, at which time points the patient will undergo a pain assessment and participate in a decision about oral dosing. It eliminates the delays and frustrations intrinsic to as-needed dosing. The second and third orders specify additional amounts of opioid to be administered on an as-needed basis for moderate or severe pain at the same time as the scheduled dose. These orders might read, “morphine 15 mg orally every 3 hours p.r.n. for moderate (pain score 4–7) pain OR morphine 30 mg orally every 3 hours p.r.n. for severe (pain score 8–10) pain.” Nurses may withhold the oral opioids for contraindications such as excessive sedation or respiratory depression. Based on this example, a patient may receive 0, 15, 30, or 45 mg of oral morphine every 3 hours. The benefit of this approach is that we are able to quickly decrease the dosage of the PCA while simultaneously identifying an oral regimen that is safe for discharge. Once the oral tier is initiated, patients are encouraged to use the oral tier in preference to PCA. With the addition of the oral tier, a PCA-delivered dose rate of less than 1 dose per hour is no longer considered a marker of a possibly too-high dose, as the delivered dose rate is expected to gradually approach 0 as patients take more of the oral medication. Many patients are able to transition to an oral opioid exclusively over a few days without any change in PCA device settings. Other patients are not able to make this transition by choice, in which case the lockout interval is incrementally increased (e.g., from 10–20 to 30–60 minutes) over 2 or 3 days. Once this transition has occurred and acute pain has either subsided or is controlled with the oral tier, both patients and providers can recognize that discharge is appropriate. The discharge regimen may be expected to remain stable or to be tapered over time. The 3 cases below describe the successful use of the oral tier. In these cases, the mean pain score is the daily mean of all 3-hour patient-reported pain scores. Additionally, total parenteral opioid is reported as milligrams per hour, as opposed to total daily dose, since patients are admitted for less than a full 24 hours on days of admission or discharge; this allows for a more accurate depiction of changes in opioid utilization throughout the hospital stay. Although we describe only 3 cases, our experience indicates that our approach is safe. Over the past 6 years we have had an average daily census of approximately 4 patients, the vast majority of whom were treated in the manner described here. Case summary 1 A 20-year-old man with chronic pain secondary to SCD (HbSS genotype) had an outpatient opioid regimen of morphine sulfate extended release (ER) 15 mg tablets, 1 tablet every 12 hours; and hydromorphone hydrochloride 8 mg tablets, 1–3 tablets every 3 hours as needed for breakthrough pain (prescribed quantity, 42 tablets for 7 days). The patient had been made aware that he was limited to an average of 6 hydromorphone tablets per day; within this limit, he could use the hydromorphone as needed for pain. His pain management regimen also included gabapentin 900 mg twice daily. On day 1 (see Figure 1 and Table 1), the patient presented to the ED and was subsequently admitted for management of VOC involving the lower-extremity joints and back. He received a total of 16 mg of i.v. morphine sulfate in the ED. His home medications (morphine sulfate ER 15 mg every 12 hours and gabapentin 300 mg 3 times daily) were continued during the admission. Intravenous hydromorphone PCA was initiated with a demand dose of 0.4 mg and a lockout interval of 10 minutes. These PCA settings were unchanged from day 1 to day 3 of his hospital stay. He also received i.v. ketorolac tromethamine 30 mg every 6 hours on days 1 through 3. At the end of day 1, including time spent in the ED, he received a total of 17.2 mg of i.v. hydromorphone hydrochloride equivalents from both PCA and i.v. bolus doses. The delivered PCA dose rate was 2.2 doses per hour. His average pain score was 7.3. Figure 1. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 1. Total parenteral hydromorphone use is reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. Total oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Figure 1. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 1. Total parenteral hydromorphone use is reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. Total oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Table 1. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 1 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 aTotal parenteral hydromorphone reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. bTotal oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Open in new tab Table 1. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 1 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral hydromorphone hydrochloride (mg)a 17.2 56.8 13.6 0 Total oral hydromorphone hydrochloride (mg)b 0 19.2 38.4 19.2 Total parenteral hydromorphone hydrochloride equivalents (mg/hr) 0.7 3.2 2.2 1.5 Average pain score 7.3 4.4 5.4 5.8 aTotal parenteral hydromorphone reported in parenteral hydromorphone equivalents using a parenteral morphine to parenteral hydromorphone conversion of 10:1.5. bTotal oral hydromorphone reported as parenteral hydromorphone equivalents using an oral hydromorphone to parenteral hydromorphone conversion of 5:1. Open in new tab On day 2, an oral tier was initiated with hydromorphone hydrochloride 8 mg by mouth every 3 hours (scheduled) and hydromorphone hydrochloride 8 mg every 3 hours as needed for moderate pain or hydromorphone hydrochloride 16 mg every 3 hours as needed for severe pain. He received 56.8 mg of i.v. hydromorphone hydrochloride, with a delivered dose rate of 6.5 doses per hour, and 96 mg of oral hydromorphone hydrochloride. His average pain score was 4.4. On day 3 the patient’s PCA was discontinued after he had received 13.6 mg of i.v. hydromorphone hydrochloride, with a delivered dose rate of 0.9 doses per hour. He received a total of 192 mg of oral hydromorphone hydrochloride. His average pain score was 5.4. On day 4, he received 96 mg of oral hydromorphone hydrochloride prior to discharge. He was discharged on his previous home opioid regimen. His average pain score was 5.8, which he considered acceptable. The patient attended a follow-up appointment at his outpatient clinic within 2 weeks of discharge. Case summary 2 A 30-year-old woman with chronic pain due to SCD (HbSS genotype) had an outpatient opioid regimen of transdermal fentanyl 75 µg/hr, oxycodone hydrochloride immediate release (IR) 10 mg tablets, 1–2 tablets every 3 hours as needed for mild or moderate pain (prescribed quantity, 100 tablets for 3 weeks); and morphine sulfate IR 30 mg tablets, 1–3 tablets every 3 hours as needed for severe pain (prescribed quantity, 40 tablets for 3 weeks). It should be noted that a regimen involving 2 short-acting opioids is very unusual at our practice site. The patient’s outpatient pain management regimen also included ibuprofen 400 mg tablets, up to 4 tablets daily as needed for pain, and transdermal lidocaine. On day 1 (see Figure 2 and Table 2) the woman presented to the ED of a nearby hospital with VOC involving both shoulders, the neck, and both wrists. The pain was refractory to ED management, including 32 mg of i.v. morphine sulfate administered over a period of 6 hours. That day she was transferred to our institution’s inpatient service, where she received a single dose of subcutaneous morphine sulfate 2 mg and was started on i.v. morphine sulfate PCA with a demand dose of 2 mg and a lockout interval of 10 minutes. Her home medications (transdermal fentanyl, transdermal lidocaine, and ibuprofen) were continued. She did not receive any doses from her PCA device, and the average pain score was 6. Figure 2. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 2. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Figure 2. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 2. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Table 2. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 2 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab Table 2. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 2 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 34 76.8 20 0 Total oral oxycodone hydrochloride (mg)a 0 5 30 10 Total parenteral morphine sulfate equivalents (mg/hr) 2.5 3.4 2.1 0.7 Average pain score 6.0 5.0 4.5 4.5 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab On day 2, the PCA lockout interval was extended to 30 minutes. An oral tier was initiated with oxycodone hydrochloride IR 10 mg every 3 hours (scheduled) and oxycodone hydrochloride IR 10 mg every 3 hours as needed for moderate pain or oxycodone hydrochloride IR 20 mg every 3 hours p.r.n. for severe pain. She received a total of 76.8 mg of i.v. morphine sulfate, with a delivered dose rate of 1.6 doses per hour, and 10 mg of oxycodone hydrochloride IR. Her average pain score was 5. On day 3, the PCA lockout interval was extended to 60 minutes. The patient received a total of 20 mg of i.v. morphine sulfate, with a delivered dose rate of 0.4 doses per hour, and 60 mg of oxycodone hydrochloride IR. Her average pain score was 4.5. On day 4, PCA was discontinued, and the patient received 20 mg of oxycodone prior to discharge. She was discharged on her previous home opioid regimen. Her average pain score was 4.5, which she considered acceptable. The patient attended a follow-up appointment at her outpatient clinic within 2 weeks of discharge. Case summary 3 A 30-year-old woman with chronic pain due to SCD (HbSS genotype) had an outpatient opioid regimen of morphine sulfate ER 30 mg every 12 hours and oxycodone hydrochloride IR 30 mg tablets, 1–3 tablets every 3 hours as needed for breakthrough pain (prescribed quantity, 70 tablets for 7 days). She presented to our institution’s infusion center with a significant increase in lower extremity and lower back pain. On day 1 (See Figure 3 and Table 3) the patient received 45 mg of i.v. morphine sulfate in the infusion center, with inadequate pain relief, and was admitted. Intravenous morphine sulfate PCA was initiated with a demand dose of 4 mg and a lockout interval of 10 minutes. Morphine sulfate ER 30 mg orally every 12 hours was continued, and an oral tier was initiated with oxycodone hydrochloride IR 30 mg every 3 hours (scheduled) and oxycodone hydrochloride IR 30 mg orally every 3 hours as needed for moderate pain or oxycodone hydrochloride IR 60 mg orally every 3 hours as needed for severe pain. She received a total of 52 mg of i.v. morphine sulfate via PCA, with a delivered dose rate of 1.4 doses per hour, and 30 mg of oxycodone hydrochloride IR. She was also started on i.v. ketorolac tromethamine 30 mg every 6 hours (scheduled). Her average pain score was 6.9. Figure 3. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 3. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Figure 3. Open in new tabDownload slide Trends in opioid usage during hospital admission in case 3. Total oral oxycodone use is reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Table 3. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab Table 3. Summary of Opioid Usage and Pain Scores Throughout Admission in Case 3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 Opioid Medication Day 1 Day 2 Day 3 Day 4 Total parenteral morphine sulfate (mg) 97 80 44 4 Total oral oxycodone hydrochloride (mg)a 15 60 90 45 Total parenteral morphine sulfate equivalents (mg/hr) 8.0 5.8 5.6 3.8 Average pain score 6.9 6.8 7.1 6.3 aTotal oral oxycodone reported as parenteral morphine equivalents using an oral oxycodone to parenteral morphine conversion of 2:1. Open in new tab On day 2, the PCA lockout interval was increased to 20 minutes. She received a total of 80 mg of i.v. morphine sulfate, with a delivered dose rate of 0.9 per hour, and 120 mg of oxycodone hydrochloride IR. Her average pain score was 6.75. On day 3, the PCA lockout interval was increased to 60 minutes. The patient received a total of 44 mg of i.v. morphine sulfate, with a delivered dose rate of 0.5 dose per hour, and 180 mg of oxycodone hydrochloride IR. Her average pain score was 7.11. On day 4, PCA was discontinued, and the patient received 90 mg of oxycodone hydrochloride IR prior to discharge. She was discharged on her previous home regimen. Her average pain score was 6.33, which she considered acceptable. The patient did not arrive for a scheduled outpatient clinic appointment and was subsequently readmitted the following week for treatment of medical problems unrelated to sickle cell crisis. Discussion The dynamic nature of acute pain in SCD is apparent in these 3 case summaries. In all 3 patients, the amount of opioid needed per hour to provide acceptable pain relief decreased dramatically over 4 days. The flexibility of the combination of PCA and an oral tier allowed patients to decrease their use of PCA and increase their use of the oral tier simultaneously while maintaining adequate pain control; it facilitated a rapid transition to an oral regimen appropriate for discharge. The willingness of patients to be discharged with pain scores greater than 4 exemplifies the accommodation of this patient population to higher pain scores as long as they have access to home opioids that they can use in a flexible manner. A limitation of this case series was the small sample size and the lack of a true comparator group. Because of this, we were unable to assess additional factors, such as whether transitioning to the oral tier made an impact on length of stay or reduced medication errors. Each of these patients and their individual opioid requirements were well known to the service providers involved. They had been previously admitted and initiated on an oral tier in the past. In implementing the oral tier approach, we have used very little naloxone to reverse suspected opioid overdose, and there have been no deaths attributed to opioid overdose. The issue of whether the success of the oral tier has contributed to our low usage of naloxone has not yet been assessed. A more robust study must be conducted to make this assessment. Conclusion Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC. Disclosures The authors have declared no potential conflicts of interest. References 1. Centers for Disease Control and Prevention . What is sickle cell disease? (revised August 2017). https://www.cdc.gov/ncbddd/sicklecell/facts.html ( accessed 2018 Aug 22 ). 2. Howard J , Telfer P. Sickle cell disease in clinical practice . London : Springer ; 2015 : 3 - 70 . Google Preview WorldCat COPAC 3. Yawn BP , Buchanan GR , Afenyi-Annan AN et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members . JAMA. 2014 ; 312 ( 10 ): 1033 - 48 . Google Scholar Crossref Search ADS PubMed WorldCat 4. National Heart, Lung, and Blood Institute . The management of sickle cell disease . Bethesda, MD : National Institutes of Health ; revised 2002 Jun. NIH publication no. 02-2117. WorldCat COPAC 5. Manwani D , Frenette PS . Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies . Blood. 2013 ; 122 ( 24 ): 3892 - 8 . Google Scholar Crossref Search ADS PubMed WorldCat 6. Payne R . Pain management in sickle cell disease . Ann N Y Acad Sci. 1989 ; 565 : 189 - 206 . Google Scholar Crossref Search ADS PubMed WorldCat 7. Strassels S , Mcnicol E , Wagner A et al. Persistent postoperative pain, health-related quality of life, and functioning 1 month after hospital discharge . Acute Pain. 2004 ; 6 ( 3 ): 95 - 104 . Google Scholar Crossref Search ADS WorldCat 8. Coley KC , Williams BA , DaPos SV et al. Retrospective evaluation of unanticipated admissions and readmissions after same day surgery and associated costs . J Clin Anesth. 2002 ; 14 ( 5 ): 349 - 53 . Google Scholar Crossref Search ADS PubMed WorldCat 9. Morrison RS , Magaziner J , McLaughlin MA et al. The impact of post-operative pain on outcomes following hip fracture . Pain. 2003 ; 103 ( 3 ): 303 - 11 . Google Scholar Crossref Search ADS PubMed WorldCat 10. Morphine sulfate package insert . Lake Forest, IL : Hospira, Inc. ; 1984 (revised 2011 Nov). WorldCat COPAC 11. Dilaudid (hydromorphone) package insert . Stamford, CT : Purdue Pharma L.P. ; 1984 Jan (revised 2016 Dec). WorldCat COPAC 12. Dumas EO , Pollack GM . Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective . AAPS J. 2008 ; 10 ( 4 ): 537 - 51 . Google Scholar Crossref Search ADS PubMed WorldCat 13. Bijur PE , Latimer CT , Gallagher EJ . Validation of a verbally administered numerical rating scale of acute pain for use in the emergency department . Acad Emerg Med. 2003 ; 10 ( 4 ): 390 - 2 . Google Scholar Crossref Search ADS PubMed WorldCat 14. Chou R , Fanciullo GJ , Fine PG et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain . J Pain. 2009 ; 10 ( 2 ): 113 - 30 . Google Scholar Crossref Search ADS PubMed WorldCat 15. Pereira J , Lawlor P , Vigano A et al. Equianalgesic dose ratios for opioids. A critical review and proposals for long-term dosing . J Pain Symptom Manage. 2001 ; 22 ( 2 ): 672 - 87 . Google Scholar Crossref Search ADS PubMed WorldCat 16. Derby S , Chin J , Portenoy RK . Systemic opioid therapy for chronic cancer pain . CNS Drugs. 1998 ; 9 ( 2 ): 99 - 109 . Google Scholar Crossref Search ADS WorldCat © American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

American Journal of Health-System PharmacyOxford University Press

Published: Nov 13, 2019

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