Fentanyl

One of the first medications we learn in anesthesia is fentanyl. If you were to ask most physicians, they would describe it as a potent rapid-onset short acting pain medication, ideal for transient discomfort but not for lasting pain because of its limited duration. Most physicians would probably dose it 25 or 50mcg a time and give it every hour or so. For severe persistent pain, most physicians would gravitate toward longer-acting opiates like morphine or hydromorphone. Before this week, this is how I viewed fentanyl.

I was assigned to a 12 hour long plastic surgery case. A woman who had bilateral mastectomies for BRCA positive breast cancer presents for breast reconstruction. These cases are tremendously long, requiring a lot of fine microdissection to ensure good blood supply to the breast flaps. I think a typical way of managing post-operative pain would be fentanyl for the start of the case and titrating hydromorphone to give a good tail coverage of pain as the patient wakes up. However, I was challenged by my attending to use only fentanyl. We modeled the pharmacokinetics of the drug and loaded the patient with quite a bit up front; instead of the usual 100mcg or 150mcg for intubation, we used 500mcg, almost a cardiac induction. We started a constant fentanyl infusion at 500mcg/hr and cut this in half every ninety minutes. Using computer simulation and modeling, we predicted the serum and effect site concentrations of fentanyl. The goal was to saturate the adipose tissue with the drug so that this became a long acting medication rather than a short acting one. Normally, a bolus of fentanyl disappears in effect because the drug goes to the fat tissues. But this time, our goal was to use the fat tissues as a depot for the drug. By the end of the case, we used over 4000mcg of fentanyl - an astonishing amount. Despite this, the patient amazingly woke up right when I said, "Open your eyes," and had absolutely no pain at all. I'd never done anything like this before, and it was a confirmation of the power of pharmacokinetic modeling.

Image of molecular structure of fentanyl is in the public domain, from Wikipedia.