Breakthrough Dosing Pharmacologic Treatment

The next step is to determine the amount of medi- cation to place in long-acting form. In general, you would choose to take 23 of the total daily dose. Thus, 23 of 108 mg PO morphine is about 72 mg PO morphine. Noting that sustained- release morphine comes in 30 mg tablets given every 12 h, you decide to use 30 mg twice daily as the long-acting dose. Next you need to calculate the breakthrough dose. Knowing that you are now going to give 60 mg per day as a long-acting dose, you can estimate the breakthrough dose at 10–20 of the long-acting dose. This gives you a dose some- where between 6 and 12 mg of immediate-release morphine. Recognizing that immediate-release morphine comes in 15 mg tablets, you choose a breakthrough dose of 7.5 mg. Hence, you have settled on the following plan: 1. Sustained-release morphine 30 mg PO twice a day 2. Immediate-release morphine 7.5 mg PO every 3 h as needed for breakthrough pain

9.4.5 Opioid Rotation

and Equianalgesia When titrating or changing opiates, it is impor- tant to start by calculating the previous day’s OME. All opioids produce analgesia by the same mechanism; thus, if provided in equianalgesic doses, they will produce the same degree of anal- gesia Table 9.2 . The most common reasons to change from one opioid to another are side effects and poor response to pain control despite appro- priate titration Drake et al. 2004 . Other indica- tions for opioid rotation include renal failure, problematic drug-drug interactions, preference or need for different route of administration or fi nancial considerations. When rotating opioids it is important to con- sider incomplete cross-tolerance. This concept takes into account that tolerance developed to one opioid does not imply complete tolerance to another. Also, the new drug may be more effec- tive due to differences in drug bioavailability or potency Pasero and McCaffery 2011 . To account for this phenomenon, a dose reduction by 25–50 should occur when rotating opioids Indelicato and Portenoy 2002 . In most cases a 25 reduction is appropriate but practitioners should use clinical judgment in determining how much of a dose reduction should occur as a result of incomplete cross- tolerance. For example, in the case of a patient who has undergone rapid increases in opioid dosing for pain subsequently deemed to be allodynia, a dose reduction of 50 may be more appropriate. Case 3 Opioid Switching You are taking care of a 50 kg young man with newly diagnosed leukemia. He’s been using mor- phine 5 mg IV every 3 h as needed for bone pain. Although he notes good pain relief, he has been itching uncontrollably. He asks you if there is anything you can do to help with his pain but keep him from itching. Plan This is one of the most common reasons to switch opioids. Although you could try a medication to treat the itching, changing the offending agent avoids polypharmacy. You decide that hydromor- phone would be a nice alternative. To calculate a dose, you fi rst need to determine the equianalge- sic dose of hydromorphone and morphine Table 9.2 : 5 1 5 10 0 75 mg IV morphine mg IV hydromorphone mg IV morphine mg IV h × = . . y ydromorphone The last step is to account for incomplete cross- tolerance. A dose reduction of 25 would provide a dose of about 0.56 mg of IV hydro- morphone. Thus, an order for 0.6 mg of IV hydromorphone every 3 h as needed for pain would be appropriate.

9.4.6 Patient-Controlled Analgesia

Calculations Patient-controlled analgesia PCA is indicated for use when pain is not controlled with oral medications, there is inability to take oral medi- cations, there is possibly poor gastrointestinal absorption of pain medications, or if the child or parent has a preference for the PCA. Studies have demonstrated PCA effectiveness in postoperative pain, but PCA use is additionally effective in burns, mucositis, bone marrow transplant and sickle cell disease Gaukroger et al. 1991 ; Mackie et al. 1991 ; Collins et al. 1996a ; Dunbar et al. 1995 ; Trentadue et al. 1998 ; Walder et al. 2001 . Children as young as 6 years are able to indepen- dently provide effective postoperative pain con- trol when taught appropriate PCA use Berde et al. 1991 . General principles and dosing of PCA are listed in Table 9.3 . Opioid naïve patients should be started at low doses of medication. Lockout intervals, which represent how often a patient can push their PCA button to receive medication, should range between 5 and 15 min. Children currently receiving opioids should have their total daily OME calculated and a proportion of that dose usually 23 divided over 24 h to give a continuous PCA rate. Demand or breakthrough doses for these patients should range from 50 to 100 of their total hourly doses. PCA dosing plans should be frequently reassessed and titrated as necessary. Initiation of PCA requires close monitoring of respiratory rate, oxygen saturation, blood pres- sure, heart rate, pain score, sedation score and nausea. Continuous pulse oximetry should be considered when PCA is started and naloxone should be available. If the child becomes somno- lent, diffi cult to arouse, has a respiratory rate 8 or oxygen saturation 92 with respiratory rate 12, or pinpoint pupils, administration of the opi- oid should be stopped and supplemental oxygen given along with naloxone. Doses can be cau- tiously restarted at 50 of the original dose once the patient is alert and if they are experiencing pain. Many institutions have developed protocols for authorized agent-controlled analgesia AACA for children 6 years which can include either nurse-controlled or caregiver-controlled analgesia as long as the caregiver is consistently available, competent, and properly educated and the authorized agent is designated in the medical order Wuhrman et al. 2007 . Case 4 PCA Calculations A 15-year-old boy with acute myelogenous leu- kemia has developed mucositis while pancytope- nic. He has been using 6 mg of IV morphine every 3 h around the clock. He tells you that the morphine has been very helpful, but his pain returns prior to the 3 h mark. He also complains that he gets somnolent immediately after the morphine dose is given. You decide that a PCA is warranted in order to give him better pain control. Plan The fi rst step is to calculate his total 24 h use of morphine: 6 8 48 mg of IV morphine doses per day mg IV morphine per day × = Next, you take 23 of that dose 48 mg × 0.67 = 32 mg and plan for it as your continuous rate. Dividing 32 mg by 24 h gives you a continuous rate of about 1.2 mgh. Next you must plan for your demand dose. There are a number of ways of doing this, but a good place to start would be to simply have the demand dose provide 50 of the hourly rate with two demand doses per hour. The goal is to return the patient to comfort with a single demand dose, thus you may need to adjust this depending on his response. Finally you need to determine a lockout interval. The timing of this is patient dependent, but since the anal- gesic onset of action for morphine occurs within 10–15 min, this is a standard lockout interval. Hence, you’ve decided on a morphine PCA with the following settings: Morphine 1.2 mgh plus 0.6 mg demand dose every 15 min as needed with a maximum hourly dose of 2.4 mg bolus + 2 demand doses Follow-up: The next morning the intern reports to you that the patient used 25 demand doses for a total daily dose of 43.8 mg ~1.8 mgh. When you speak with the patient, he tells you that he is overall comfortable, but he sometimes needs two demand doses to return to comfort, especially upon waking from sleep.