Lower Mortality Associated With Opioid-Sparing Prostatectomy

Jenni Laidman

December 18, 2013

For patients undergoing prostatectomy, an opioid-sparing approach to anesthesia was associated with a lower risk for systemic prostate cancer progression and lower overall mortality than general anesthesia, according to the largest study of its kind.

The results were published online on December 16 in the British Journal of Anaesthesia.

Juraj Sprung, MD, PhD, professor of anesthesiology at the Mayo Clinic in Rochester, Minnesota, and colleagues compared outcomes for 1642 prostatectomies performed with an opiate-sparing approach and 1642 performed with general anesthesia.

For the opiate-sparing approach, general anesthesia was supplemented with neuraxial block, and it typically included a single intrathecal spinal injection of bupivacaine with either morphine or hydromorphone.

This requires far less systemic opioid administration than general anesthesia alone, said Dr. Sprung. He explained that the general anesthesia was usually induced with propofol or sodium thiopental, fentanyl, midazolam, and succinylcholine or vecuronium, and was maintained with isoflurane, desflurane, or sevoflurane, with or without nitrous oxide.

Pathologic stage, Gleason score, and positive lymph nodes were identical in the 2 groups, but American Society of Anesthesiologists physical status and the rate of several comorbid conditions were greater in patients in the general anesthesia group. These patients also had a greater rate of positive margins than those in the opiate-sparing group (27% vs 19%; < .001), and a greater likelihood of radiation adjuvant treatment (3% vs 2%; = .001).

All study patients underwent radical retropubic prostatectomy, and median follow-up was 9 years.

Risk for Cancer Progression Increased 3-Fold

After adjustment for comorbidities, positive surgical margins, and adjuvant hormonal and radiation therapy within 90 days of surgery, the researchers found that general anesthesia was associated with nearly 3 times the risk for systemic progression (hazard ratio [HR], 2.81; = .008) and a 30% increased risk for mortality from any cause (HR, 1.32; = .047), compared with the opioid-sparing approach.

The difference in prostate-cancer-specific deaths failed to reach significance (HR, 2.2; = .091), but relatively few patients in the study died from cancer in either group, the researchers report.

Prostate cancer typically recurs in ~25% of all radical retropubic prostatectomy patients, the researchers note. Opioids interfere with the body's natural killer cells, one of the primary immune system weapons against cancer. Systemic morphine alters lymphocytic proliferation, but intrathecal morphine does not affect peripheral lymphocytes, they explain.

The fact that cancer-specific survival did not reach statistical significance was expected, given the nature of prostate cancer growth. "Prostate cancer has a slow progression, so over 10 years, not that many people die. That's a problem — not for the patient, but for the study. There's not enough power here to take that into account," Dr. Sprung said.

Still, this study is far larger than previous comparisons, and had ample power to identify associations that other studies were too small to detect, he noted. Three previous studies have examined the relation between neuraxial anesthesia and cancer outcome in prostatectomy. The largest of these, which involved 261 patients, reported a reduced risk for cancer progression but no difference in recurrence-free, cancer-specific, or overall survival.

Intrathecal anesthesia allows physicians to "drastically reduce the amount of opiates administered postoperatively," Dr. Sprung explained, and several previous studies have documented its ability to control pain better than general anesthesia alone. However, in this study, pain scores were not evaluated.

Study patients were drawn from the Mayo Clinic Radical Prostatectomy Registry, the Mayo Clinic's anesthesia database, and electronic medical records. Patients diagnosed from 1991 to 2005 were evaluated.

"We found a significant association between this opioid-sparing technique, reduced progression of the prostate tumor, and overall mortality," Dr. Sprung said in a statement. "Provided future studies confirm what we found in this study, this might become a standard of care for pain management in patients undergoing cancer surgery."

A prospective study would be the ideal way to demonstrate the benefit of this anesthetic approach, Dr. Sprung told Medscape Medical News, but successful recruitment for such a study is unlikely. Prospective studies looking at this issue have already been canceled because of poor recruitment, he said.

In the meantime, the Mayo Clinic is extending the research on opiates to surgery for bladder cancer, matching opiate-sparing anesthesia in some 400 patients to general anesthesia in 400 to 800 patients.

The authors have disclosed no relevant financial relationships.

Br J Anaesth. Published online December 16, 2013. Abstract


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