Current Concepts of Phenylpiperidine Derivatives Use in the Treatment of Acute and Chronic Pain

Phenylpiperidines are a chemical class of drugs with a phenyl moiety directly attached to piperidine. These agents have an important role in many aspects of medicine including anesthesia and pain medicine. After the development of meperidine, fentanyl, which is a second generation synthetic phenylpiperidine series opioid, was synthesized and introduced into clinical anesthesia practice as fentanyl citrate in 1968. Fentanyl-mediated or modulated responses involve action at the muopioid receptor as an agonist at the dorsal horn inhibiting ascending pain pathways in the rostral ventral medulla, increasing pain threshold, and producing both analgesic and sedative effects. Since fentanyl is metabolized mainly via CYP3A4, potential adverse effects can occur with concomitant use of any drug which affects CYP3A4 activity. Discontinuation of CYP3A4 inducers can also result in an increase in fentanyl plasma concentration. Fentanyl-based formulations can be administered via intravenous, intramuscular, transdermal, transmucosal, and neuraxial routes. We describe the clinical utility of remifentanil, an ultra short-acting analgesic and newer formulations of sufentanil currently being evaluated for acute pain management. We examine the routes of administration and clinical considerations, including the role of opioids such as fentanyl as a natural killer cell suppressive agent. Fentanyl and other opioids have been shown to potentiate propagation of infection and cancer. In recent years, fentanyl and other phenylpiperidine formulations have been developed and successfully marketed for chronic pain management. Because all opioids have complex physiological responses and potential drug-drug interactions, the clinician should appreciate all aspects of this drug class and consider all available options in appropriate clinical settings. Key words: Fentanyl, remifentanil, sufentanil, opioids, analgesics, pain, perioperative formulations, management

Incidence of Serotonin Syndrome in Patients Treated with Fentanyl on Serotonergic Agents

Background: There has been a recent surge in the literature highlighting the association of fentanyl as precipitating serotonin syndrome in patients on a serotonergic agent. Objective: The purpose of our study was to understand the incidence of serotonin syndrome in patients who receive fentanyl while on serotonergic agents. Study Design: This retrospective analysis was conducted from 2012 to 2013 after approval from the Institutional Review Board. We searched for all patients that had received a serotonergic agent and were admitted to the hospital during the study period. Next, we split these patients into 2 groups by placing all patients who had received fentanyl and a serotonergic agent into one group. We then searched for any of the Hunter Serotonin Toxicity Criteria in the records of patients that had received both fentanyl and a serotonergic agent. Further, we searched for all patients with serotonin syndrome mentioned in their records. Setting: This study was conducted at a 900 bed tertiary care academic center. Results: Over the 2 year study period, 112,045 patients were on a serotonergic agent, and 4,538 of these patients were treated with both fentanyl and a serotonergic agent. A search for Hunter’s Criteria through the records of the patients receiving both fentanyl and a serotonergic agent revealed 23 patients had been documented with some of these symptoms. On detailed chart review, only 4 [95% CI 1 – 10] of these patients truly met Hunter’s Criteria for serotonin syndrome. We then searched all admissions for a diagnosis code of serotonin syndrome during the study period. Five additional cases of serotonin syndrome were found, but none of these patients were treated with fentanyl. Limitations: Some of the limitations of our study include that it represents a single institution, although it is a large academic center. An inherent limitation may be the under diagnosis of serotonin syndrome. Conclusion: The incidence of serotonin syndrome in patients who receive both fentanyl and a serotonergic agent is low. Key words: Fentanyl, serotonin syndrome, serotonergic drugs, opioids, SSRI, antidepressant