Opioid-induced Neurotoxicity Research Articles

The Opioid Rotation Ratio (ORR) from transdermal fentanyl (TDF) to strong opioids in cancer patients.

182 Background: Despite being the most frequently prescribed strong opioid by oncologists, there is a lack of knowledge of the accurate the opioid rotation ratio (ORR) from transdermal fentanyl (TDF) to other strong opioids in cancer patients. Opioid rotation (OR) from TDF to other strong opioids is performed very frequently in cancer patients for uncontrolled pain or opioid induced neurotoxicity (OIN). The aim of our study was to determine the ORR of TDF to other strong opioids, as measured by morphine equivalent daily dose (MEDD). Methods: In this ad hoc analysis, we reviewed 2471 consecutive patient visits to the supportive care center of a tertiary cancer center in 2008 for an OR from TDF to other strong opioids by a palliative medicine specialist. Information regarding demographics, Edmonton Symptom Assessment Scale (ESAS), and MEDD were collected in patients who followed-up within 6 weeks. Linear regression analysis was used to estimate the ORR between TDF dose and net MEDD (MEDD after OR minus MEDD of breakthrough opioid used along with TDF before OR). Successful OR was defined as 2-point or 30% reduction in pain score and continuation of the new opioid at follow up. Results: 47/2471 patients underwent OR from TDF to other opioids and followed-up within 6 weeks. The median age was 54 years, 53% were male, and 77% had advanced cancer. The median time between OR and follow up was 14 days. Uncontrolled pain (83%) followed by OIN (15%) were the most frequent reasons for OR and 77% had a successful OR with significant improvement in ESAS pain and symptom distress scores. In patients with OR and no worsening of pain at follow-up (n = 41), the median ORR (range) from TDF mg/day to net MEDD was 100 (12.5-217), TDF mcg/hour to net MEDD was 2.4 (0.3-5.2), and correlation of TDF dose to net MEDD was .60 (P < 0.0001). Conclusions: The median ORR from TDF mg/day to MEDD is 100 and from TDF mcg/hour to MEDD is 2.4. Further validation studies are needed.

The conversion ratio (CR) for opioid rotation (OR) from strong opioids to transdermal fentanyl (TDF) in cancer patients.

9612 Background: Cancer patients frequently undergo OR for uncontrolled pain or opioid induced neurotoxicity (OIN). TDF is one of the most common opioids prescribed to cancer patients. However, the...

Factors Associated With Survival After Opioid Rotation in Cancer Patients Presenting to an Outpatient Supportive Care Center

ContextData on cancer outpatients undergoing opioid rotation (OR) are limited. Understanding the characteristics of patients who do not follow up after OR could facilitate optimization of OR. ObjectivesTo compare the characteristics and overall survival of patients with and without follow-up after OR. MethodsIn this preliminary ad hoc analysis, we reviewed consecutive patients who presented to our supportive care center in 2008 for OR. Data about demographics, scores on the Edmonton Symptom Assessment System and Memorial Delirium Assessment Scale (MDAS), opioid use, and indications for OR were collected. Univariate logistic regression models were used to determine the factors associated with follow-up. Kaplan-Meier curves were used to evaluate survival. ResultsOf the 190 patients who underwent OR, 120 (63%) had a follow-up visit. Follow-up visits occurred more frequently in patients with localized disease (89%; 24/27; P = 0.0023), history of substance abuse (100%; 12/12; P = 0.0085), performance status ≤ 2 (66%; 97/146; P = 0.0002), no delirium (67%; 118/177; P = 0.002), and uncontrolled pain as reason for OR (66%; 97/146; P = 0.036). Patients who underwent OR for opioid-induced neurotoxicity (44%; 15/34; P = 0.01) and had higher MDAS scores (P = 0.0009) were less likely to follow up. Both follow-up after OR (P < 0.001) and successful OR (P = 0.012) were associated with longer overall survival, with a difference in median survival of 4.3 and 3 months, respectively. ConclusionOur preliminary study suggests that patients with advanced cancer, poorer performance status, opioid-induced neurotoxicity, and higher MDAS scores are less likely to follow up after OR and may have shorter overall survival and, therefore, require closer follow-up. Patients with unsuccessful OR also may have a shorter overall survival. Further studies are warranted.

Opioid-Induced Neurotoxicity

Opioid-Induced Neurotoxicity

Palliative care research: Lessons learned by our team over the last 25 years

Background: In the last 25 years, palliative care has made major progress as an interdisciplinary specialty that addresses quality-of-life issues for patients with life-limiting illnesses and their families. Research by numerous investigators has contributed to our increasing body of knowledge to support an evidence-based practice. Aim: We highlight some lessons learned by our group in the process of conducting palliative care research, focusing in particular on symptom assessment; the management of pain, fatigue, cachexia, dyspnea, delirium, and opioid-induced neurotoxicity; and outcomes of our palliative care program. Design: Narrative review of selected literature, focusing on studies conducted by our group. Data sources: This article is based on the Second Vittorio Ventafridda Memorial Lecture by Dr Eduardo Bruera, delivered at the European Association for Palliative Care, Trondheim, Norway on 8 June 2012. Results: For each topic, we review some of the pivotal studies in palliative care, discuss the challenges in research design, and outline possible directions for future research. Conclusions: We conclude by sharing some of what we learned about the processes, pearls, and pitfalls of palliative care research.

Frequency, Outcome, and Predictors of Success Within 6 Weeks of an Opioid Rotation Among Outpatients with Cancer Receiving Strong Opioids

Opioid rotation is used to treat uncontrolled pain and/or opioid-related adverse effects. Our aim was to determine the frequency, indications, outcomes, and predictors of successful opioid rotation in outpatients with cancer. Medical records of consecutive outpatients with cancer who received strong opioids and returned for follow-up visit within ≤6 weeks to our supportive care center from January to December 2008 were reviewed. Data on patient characteristics, symptoms, opioid use, indications for opioid rotation, outcomes, and morphine equivalent daily dose were collected. Successful opioid rotation was defined as a two-point or 30% reduction in the symptom score or the resolution of opioid-induced neurotoxicity and continuation of the new opioid at follow-up. Opioid rotation was performed in 120 of 385 patients (31%). The median patient age was 55 years. There were 6/120 patients with missing data. Of the 114 evaluable patients, 68 (60%) were men, 81 (71%) were white, 27 (24%) had gastrointestinal cancer, and 90 (80%) had advanced-stage disease. The median Eastern Cooperative Oncology Group score was 1 (interquartile range: 1-2) and the median time between opioid rotation and follow-up was 14 days (interquartile range: 7-21 days). The most common indications for opioid rotation were uncontrolled pain (95/114; 83%) and opioid-induced neurotoxicity (13/114; 12%). A total of 35 patients (31%) had partial opioid rotation. The median improvements in pain and symptom distress score were -2 (interquartile range: -4 to 0; p < .001) and -5 (interquartile range: -14 to 7; p = .004), respectively. The morphine equivalent daily dose did not change significantly after opioid rotation (p = .156). A total of 65% of patients (74/114) had successful opioid rotation. There were no clinically significant independent predictors for successful opioid rotation. Opioid rotation was conducted in 31% of outpatients with cancer, with a 65% success rate. The most frequent reason for opioid rotation was uncontrolled pain. There were no independent predictors for successful opioid rotation.

Frequency, indications, outcomes, and factors associated with successful opioid rotation in cancer patients presenting to an outpatient supportive care center.

e19599 Background: Opioids are first line medications for cancer pain. Opioid rotation (OR) is recommended for uncontrolled cancer pain (UCP) and opioid induced neurotoxicity (OIN). Limited data exist on frequency, indications and outcomes of OR in ambulatory cancer patients in outpatient setting. Methods: We reviewed consecutive outpatient visits to the Supportive Care Center in 2008 for OR. Data regarding demographics, Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale, pain characteristics, opioid use, indication for OR, outcomes, morphine equivalent daily dose (MEDD) and supportive counseling was collected in all patient visits who followed up within 5 weeks of OR. Successful OR was defined as a 2 point or 30% reduction in ESAS symptom score, resolved symptoms of OIN and continuation of new opioid at follow up. Stepwise logistic regression analysis was performed to determine factors associated with successful OR. Results: 244/2471(10%) patient visits had OR and 142 (58%) were followed up within 5 weeks. 40% (57/142) were consult visits. 74% (105/142) were white, 60% (85/142) male. Median age and performance status were 55 and 1. GI (24%) and lung (22%) were the most common cancer types with 77% (110/142) advanced cancer. Median time (Q1-Q3) between OR and follow up was 14 (7-21) days. Most common indications for OR were UCP 82% and OIN 13%. 34% had partial OR and 16% had more than one reason for OR. Pain characteristics were 49% nociceptive, 21% mixed and 11% neuropathic. Median (Q1-Q3) pain and symptom distress score improved: -2 (-4-0, P=.003) and -5 (-14-7, P=.004). Median MEDD (Q1-Q3) decreased from 162 (90-287) to 156 (90-280, P=.82). 66% (94/142) had successful OR. Fentanyl (34%) before and Methadone (55%) after OR were most common opioids. 17% (24/142) had another OR at follow up visit. High MEDD (P=.05) prior to OR was associated with successful OR. Conclusions: 10% of outpatient visits had OR with a 66% success rate in treating UCP and OIN. Further research is needed to determine predictors of successful OR.

Opioid Induced Neurotoxicity in a Patient With Cancer Related Pain (758)

1.Recognize the emerging phenomenon of opioid induced neurotoxicity in patients who are receiving opioids for cancer related pain.2.Understand how to evaluate suspected opioid induced neurotoxicity, and how to manage patients with this disorder. Clinician education has resulted in appropriate increases in opioid use for cancer related pain. This has led to enhanced symptom control, but also to the emergence of opioid induced neurotoxicity (OIN). A 57 year old man with prostate cancer presented with low back pain and tenderness over back and right femur. Hydromorphone patient controlled analgesia (PCA) was started, bolus dose of 0.4mg intravenously (IV), 10 minute lockout, no basal rate (0.4/10/0). His home methadone dose (150mg twice daily) continued. MRI revealed diffuse bony metastases and right femoral neck fracture. He underwent radiation to spine and right total hip replacement. Pain improved, but 6 days later PCA was titrated to 20/10/9 with worsening pain. The following day, he had muscle spasms and confusion. He was alert but delirious, with 16 beats of myoclonus per minute in his arms. Labs were unremarkable. OIN was diagnosed. PCA was stopped for 90 minutes, then resumed 50% of prior bolus dose and no basal (10/10/0). Methadone was continued. Lorazepam was scheduled. Symptoms resolved within 48 hours. Neuroexcitatory effects of opioids may be seen in any patient. Comorbid conditions may precipitate OIN. Effects are caused by 3-glucuronide opioid metabolites, which have no analgesic effect and accumulate rapidly. Myoclonus is usually the presenting symptom, and if missed can progress to hyperalgesia, delirium, and tonic-clonic seizures. Clinicians may mistakenly treat hyperalgesia with higher opioid doses and facilitate progression of OIN. Evaluation includes blood work, physical exam, and thorough chart review of opioid dosages and dose changes. Exacerbating factors should be treated. If pain remains controlled, reduce opioid dose. Initiate benzodiazepines to raise seizure threshold. If pain is uncontrolled, rotate to a structurally dissimilar opioid at 25-50% of the morphine equianalgesic dose. OIN due to methadone is exceedingly rare. Naloxone does not treat OIN, and should not be used.

Opioid-Induced Neurotoxicity in the Hospice Patient

A potential adverse effect of opioids in the hospice patient is a condition called opioid-induced neurotoxicity. It is a syndrome characterized by symptoms such as severe pain, tremors, seizures, confusion, and hallucinations and is easily missed by unaware clinicians. Hospice patients are particularly at risk because of high doses of opioids and some degree of renal failure. Retained opioid metabolites may cause neuroexcitatory and antianalgesic adverse effects. In this instance, the opioids can be a cause of patient suffering. As pain levels increase, the instinct of the provider is to increase the dose of the opioid. Unfortunately, this augments the pool of metabolites and further amplifies the symptoms. This in turn may lend to cyclical increases in opioid doses by well-meaning healthcare professionals. This article examines recent evidence-based literature regarding opioid-induced neurotoxicity and discusses clinical implications for nurses who care for the terminally ill. Key points of assessment and a framework of management strategies are provided to aid in effective symptom management.

The Assessment and Management of Delirium in Cancer Patients

Delirium remains the most common and distressing neuropsychiatric complication in patients with advanced cancer. Delirium causes significant distress to patients and their families, and continues to be underdiagnosed and undertreated. The most frequent, consistent, and, at the same time, reversible etiology is drug-induced delirium resulting from opioids and other psychoactive medications. The objective of this narrative review is to outline the causes of delirium in advanced cancer, especially drug-induced delirium, and the diagnosis and management of opioid-induced neurotoxicity. The early symptoms and signs of delirium and the use of delirium-specific assessment tools for routine delirium screening and monitoring in clinical practice are summarized. Finally, management options are reviewed, including pharmacological symptomatic management and also the provision of counseling support to both patients and their families to minimize distress.

When Pain Management Becomes Toxic: Recognizing, Diagnosing, and Treating Opioid-Induced Neurotoxicity (334)

When Pain Management Becomes Toxic: Recognizing, Diagnosing, and Treating Opioid-Induced Neurotoxicity (334)

Opioid-Induced Neurotoxicity: Too Much of a Good Thing

Opioid-Induced Neurotoxicity: Too Much of a Good Thing

Management of Opioid-induced Neurotoxicity

Management of Opioid-induced Neurotoxicity

Opioid use in cancer pain. Is a more liberal approach enhancing toxicity?

The majority of cancer patients develop pain before death. This pain has been shown to be underdiagnosed and undertreated. Opioid use has increased in the past 20 years in both developing and developed countries. The changing pattern in opioid use has resulted in the emergence of neurotoxicity as a major side effect of the treatment of cancer pain. The syndrome of opioid-induced neurotoxicity (OIN) encompasses delirium, hallucinosis, myoclonus/seizures and hyperalgesia. Increased vigilance can lead to the timely diagnosis of OIN, and strategies for its treatment can be implemented with encouraging results. Identification and modification of risk factors for the development of OIN can help in its prevention and improve the quality of life in advanced cancer patients.

Side-effects of opioids in chronic pain treatment

The emergence of opioid-induced neurotoxicity has gained increasing recognition in the literature in the past decade. Exciting developments at the receptor and intracellular level have revealed some insights into the potential mechanisms underlying this phenomenon. The hitherto reported clinical benefits of opioid rotation and dose reduction in the treatment of opioid toxicity warrant further clarification in prospective studies, particularly in relation to their relative value.