Very high doses of an opioid may produce myoclonus. One group of investigators reported the development of acute confusion, restlessness, myoclonus, hallucinations, and hyperalgesia due to an inadvertent administration of high-dose intravenous fentanyl. These symptoms were successfully treated with several doses of 0.1 mg to 0.2 mg of intravenous naloxone followed by a continuous infusion of intravenous naloxone (0.2 mg per hour).
Evaluation of the patient with myoclonus includes ruling out other known causes such as surgery to the brain, placement of an intrathecal catheter, AIDS dementia, hypoxia, chlorambucil, metoclopramide, and a rare paraneoplastic syndrome called opsoclonus-myoclonus. The etiology of the paraneoplastic syndrome can also be viral; symptoms include myoclonus, opsoclonus, ataxia, and encephalopathic features. The extent of the work-up to determine the cause of myoclonus varies with the goals of care.
When opioids are implicated in the development of myoclonus, hydration and rotation to other opioids are the primary treatments. There is great variability in individual response to opioids; thus, different agents may be more likely to produce myoclonus or other adverse effects. Because cross-tolerance between opioids is not complete, empirical evidence suggests that after an equianalgesic dose is calculated, that dose should be reduced by approximately 25%, then titrated upward to meet the patient's analgesic needs.
In patients with rapidly impending death, the health care provider may choose to treat the myoclonus rather than make changes in opioids during the final hours. Little research is available regarding the most effective agents for reducing myoclonic jerking. Benzodiazepines, including clonazepam, diazepam, and midazolam, have been recommended.[15,36,37] The mechanism of action of benzodiazepines is through binding to gamma-aminobutyric acid type A receptors within the central nervous system (CNS), leading to CNS depression. At higher doses, benzodiazepines may also limit repetitive neuronal firing, similar to several anticonvulsant compounds such as carbamazepine.
The anticonvulsant gabapentin has been reported to be effective in relieving opioid-induced myoclonus, although other reports implicate gabapentin as a cause of myoclonus.[39,40][Level of evidence: III] The antispasmodic baclofen has been used to treat myoclonus due to intraspinal opioid administration. Dantrolene has been used, but it produces significant muscle weakness and hepatotoxicity. In one small randomized study, hydration was found to reduce myoclonus.[Level of evidence: I] In cases of severe myoclonus, palliative sedation may be warranted.
Dyspnea, described as shortness of breath or air hunger, is a common symptom in people with cancer during the final days or weeks of life. The prevalence of dyspnea in adults diagnosed with cancer varies from 21% to 90%, correlated with lung cancer and advanced disease.[Level of evidence: II] Dyspnea may predict shortened survival. Patients with cancer presenting to an emergency center for treatment of dyspnea had a median overall survival of 12 weeks. Patients with lung cancer had a significantly shorter survival (4 weeks) than did patients with breast cancer (22 weeks). In another study, patients presenting to an emergency department with cancer-related dyspnea who were at greatest risk of imminent death were those with an elevated pulse (100 or more beats per minute) and increased respiratory rate (more than 28 breaths per minute), with a predicted mean survival of less than 2 weeks.