Managing High Dose Sufentanil in a Suffering Patient
Article Outline
To the Editor:
Patients in severe pain, on high opioid doses, and exhibiting cognitive failure, are some of the most challenging patients to manage. Often there is uncertainty about the underlying cause of the pain, such as the role of physical vs. psychosocial factors and the role of opioid tolerance or substance abuse. Multiple medications are often administered in the attempt to improve the patient's situation by affecting multiple pain pathways. Clinicians rightfully become nervous when dealing with opioid doses that have become markedly escalated. Often there are few resources to turn to for guidance as the situation falls out of the norm from which the guidelines for opioid use have been determined.
Sufentanil, a piperadine-derived mu agonist opioid, is a more potent congener of fentanyl that was approved for clinical use by the U.S. Food and Drug Administration in 1984.1 It has been used extensively for surgical anesthesia and also as a neuraxial analgesic for acute pain.2, 3, 4 However, experience with its use as a systemic analgesic for chronic pain is limited.2 We report a challenging case of a patient receiving high doses of intravenous (IV) sufentanil.
Case Report
A 24-year-old Hispanic female, on active duty in the Army, had been diagnosed with Hodgkin's disease three years earlier. She was married and had a two-year-old daughter but there was history of a strain in her relationship with her husband. No history of substance abuse was apparent. She had undergone multiple chemotherapies, and mediastinal radiotherapy, with only partial response. Approximately three months before presentation, she had developed progressive left-sided pelvic pain, for which she commenced palliative radiotherapy. She was able to receive only two out of 20 fractions of radiation to her pelvis as she developed transfusion-dependent anemia and thrombocytopenia. At the time she was admitted to the hospital, her pain was rated 10/10 on a numeric rating scale and was described as a constant ache in the left lower abdomen and pelvis, aggravated by movement and radiating down to the lower thigh area. She had limited ability to ambulate. On examination, she was found to have a left lower quadrant abdominal mass, left lower extremity swelling but no objective weakness or sensory changes. Imaging studies had earlier shown sclerosis of the left ischium, acetabulum, and inferior pubic ramus, as well as a soft tissue mass involving the left obturator muscle and marked adenopathy of the left groin. Abdominal plain films showed no evidence of constipation, obstruction, ileus, or perforation. She was on a combination of multiple opioids, including hydromorphone, methadone, and oral transmucosal fentanyl citrate. All of these opioids were initially prescribed on an as needed basis. The patient was also taking lorazepam for anxiety. The hydromorphone was switched to IV via patient-controlled analgesia (PCA) and methadone was discontinued. She continued to report intractable pain, and after a few days on escalating doses of hydromorphone, she underwent an opioid rotation to sufentanil via PCA together with transdermal fentanyl. After 10 days, the patient continued doing poorly and the palliative care team was consulted.
After initial assessment, she was transferred to the Palliative Care Unit (PCU). At this time, she appeared drowsy but arousable, with poor concentration and disorientation to time. Her Mini-Mental State Examination score was 5/30, indicating profound cognitive impairment. Due to the patient's cognitive decline, pain was rated by the nurse, with a resulting score of 7/10 on the Edmonton Symptom Assessment System. She was receiving sufentanil PCA with a basal rate of 100 mcg/h, a self-administered demand dose of 50 mcg every 10
minutes and a nursing bolus of 20 mcg/h as needed. She was also receiving a total of 250 mcg/h of transdermal fentanyl via patches, which were changed every 72hours. Other medications included a lorazepam infusion of 0.5mg/h, clonazepam 0.5mg orally twice daily, dronabinol 12.5mg orally twice daily, and dexamethasone 4mg daily. Her cognitive impairment was attributed to opioid toxicity secondary to opioid escalation together with multiple centrally, acting drugs. A strong element of anxiety was evident based on the history. The team learned that the patient had recent communication of the bad news that her disease was refractory to treatment. This had caused further stress to the patient and her family. Her primary service had then discussed and documented her DNR status at that time. Her drug-induced delirium was deemed the more pressing clinical problem. The palliative care team was in agreement on stopping her dronabinol and both benzodiazepines. We then looked to the more challenging task of safely rotating her to an alternative opioid.
The patient's opioid doses were extremely high. We decided to rotate sufentanil and transdermal fentanyl to methadone as the patient's sole opioid, based on the patient's previously tolerating this drug well and the significant potency of methadone seen with rotation from high doses of morphine, as reported by Ripamonti et al.5 We chose to rotate the sufentanil dose of the basal rate alone and not factor into the calculations contributions from demand and nursing boluses of sufentanil, as these, we believed, were heavily influenced by the patient's anxiety. The demand doses were discontinued due to the patient's impaired cognition. Due to the very large doses of opioids involved, we chose to gradually decrease the sufentanil PCA and fentanyl patches and introduce the oral methadone over three days (Table 1).
Table 1. Sufentanil/Fentanyl Rotation to Methadone
| Day | Sufentanyl/Fentanyl | Methadone (Oral) |
|---|---|---|
| 1 | Reduce sufentanil basal rate by 1/3 from 100 mcg/h to 60 mcg/h | Start at 1/3 target dose 50mg q8hour |
| Reduce fentanyl patch by 1/3 from 250 mcg/h to 150 mcg/h q72hour | ||
| 2 | Reduce sufentanil basal rate by 1/3 from 60 mcg/h to 30 mcg/h | Increase dose by further 1/3 to 100mg q8hour |
| Reduce fentanyl patch by further 1/3 from 150 mcg/h to 75 mcg/h q72hour | ||
| 3 | Stop sufentanil PCA and fentanyl patch | Increase to target dose of 150mg q8hour |
The day following these changes, the patient had noticeable improvement in her functional status and cognition, with her Mini-Mental State Examination score improving to 23/30. By the eighth day on the PCU, she exhibited normal cognition, with a Mini-Mental State Examination of 26/30. She was able to receive other modalities to improve her pain, such as expressive-supportive counseling and visits from the chaplain as well as a family meeting. She voiced some of her significant fears that appeared to be contributing to her anxiety and expression of pain, including fear of what was going to happen to her two-year-old daughter, and her concern about tension between her husband and her mother and sister. She remained on the PCU for a total of 13 days, during which time it was possible to gradually reduce her methadone dose. During the last four days on the PCU, she rated her pain as a 1, 4, 4, and 1, respectively, on the 0–10 scale, but complained of anorexia, poor overall well-being, and insomnia. She was discharged home to hospice, ambulatory with minimal assistance, on oral methadone 30mg every eight hours and 10mg every two hours as needed for breakthrough pain.
Comment
Two main points emerge from this case. The first concern we faced was extremely high doses of an opioid we use rarely, sufentanil via PCA. Although other strong opioids could have been used to rotate the patient off of sufentanil, methadone can be a particularly helpful drug in this setting as more manageable opioid doses result with the benefit of less future risk of opioid toxicity.
For the purposes of illustration, we include the rationale we used in calculating the opioid rotation. A review of the literature shows few studies that address the relative potency of systemically administered sufentanil in patients receiving opioids chronically. Older literature reports sufentanil as being 10 times more potent than fentanyl.1, 6, 7 Paix et al. reported a series of 11 cancer patients who were rotated from morphine continuous subcutaneous infusion (CSCI) to fentanyl CSCI due to unacceptable opioid side effects. The findings resulted in a recommendation that 150–200 mcg of fentanyl is equivalent to 10mg morphine in nonopioid-naive chronic cancer patients. Two of the patients in this series required fentanyl CSCI to be changed to sufentanil CSCI due to the volume being too large for the portable syringe driver. The clinically derived sufentanil to fentanyl potencies were 24:1 and 16:1 in these two patients.8 However, Reynolds et al. investigated the relative analgesic potency of fentanyl and sufentanil IV in 41 patients on long-term opioid management for chronic pain and found sufentanil to be approximately 7.5 times as potent as fentanyl.2 In performing the calculations for the opioid rotation, we elected to err on the side of underdosing rather than overdosing with the new opioid, and, therefore, used the findings of Paix et al. to convert the 2,400 mcg of IV sufentanil a day that the patient was receiving in the PCA basal rate to an equivalent dose of fentanyl by multiplying by a factor of 20 (i.e., between 24:1 and 16:1). The result was a calculated equivalent dose of IV fentanyl of 48,000 mcg per day. We then calculated an equivalent dose of IV morphine based on the established conversion ratios reported at www.palliative.org/PC/ClinicalInfo/AssesmentTools/, as we have had prior experience using this ratio (i.e., fentanyl 100 mcg IV=morphine 10mg IV), rather than using the recommendation of Paix et al. for converting between fentanyl and morphine. This resulted in an equivalent dosage of 4,800mg of IV morphine. This number was multiplied by 2.5 to achieve an oral morphine equivalent daily dose (MEDD) of 12,000mg based on IV morphine being approximately 2.5 times more potent than oral morphine. We elected not to add in the contributions of the fentanyl patches as they were relatively small by comparison (250 mcg fentanyl patch=500mg oral morphine). Based on this extremely high MEDD and the data extrapolated from the study of Ripmonti et al., we divided the MEDD by a factor of 20 (methadone being approximately 20 times more potent than morphine at this high MEDD) and then further reduced the dose by 25% to be cautious.5 This resulted in an equivalent oral daily dose of methadone of 450mg.
The second point is that psychosocial distress can be expressed as pain and may not be effectively managed with medications. Escalation of opioids and sedatives can exacerbate the situation by causing sedation and delirium. Opioid rotation and reduction of the dose, together with discontinuing the centrally acting agents, resulted in a return to normal cognition and patient then being able to engage in psychosocial interventions. The resulting reduction of the patient's opioid dose and pain complaint confirmed the initial clinical suspicion that a significant component of “total pain” or suffering was driving the patient's distress.
References
- . The emerging role of the fentanyl series in the treatment of chronic cancer pain. In: Portenoy RK, Bruera E editor. Topics in palliative care. New York: Oxford University Press; 1997;p. 177–194
- Relative analgesic potency of fentanyl and sufentanil during intermediate-term infusions in patients after long-term opioid treatment for chronic pain. Pain. 2004;110:182–188
- Comparison of continuous epidural infusion of ropivacaine and sufentanil with intravenous patient-controlled analgesia after total hip replacement. Anaesthesia. 2001;52:1189–1193
- A comparison of intrathecal fentanyl and sufentanil for labor analgesia. Anesthesiology. 2002;96:1070–1073
- Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio?. J Clin Oncol. 1998;16:3216–3221
- . Opioids in analgesia. In: Estafanous FG editors. The development of new synthetic narcotics. Boston, MA: Butterworth; 1984;p. 40
- . Narcotic intravenous anesthetics. In: Miller RD editors. Anesthesia. 3rd ed.. New York: Churchill Livingstone; 1990;pp. 281–366
- Paix A, Coleman A, Lees J, et al. Subcutaneous fentanyl and sufentanil infusion substitution for morphine intolerance in cancer pain management. Pain 63:263–269.
PII: S0885-3924(08)00212-1
doi:10.1016/j.jpainsymman.2008.01.006
© 2008 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
