Author: Michael Vlessides
Women who undergo a mastectomy with a paravertebral block and propofol have significantly lower rates of five-year mortality and cancer recurrence than their counterparts receiving volatile anesthetics, according to a new study.
With these findings, the researchers urged their colleagues to consider using paravertebral blocks in these patients, even if it means obtaining training in ultrasound-guided regional anesthesia.
“This is not the first study of its kind; others have done it before,” said Stuart A. Grant, MB ChB, a professor of anesthesiology at Duke University Medical Center, in Durham, N.C. “However, they were usually underpowered to demonstrate any effect and didn’t follow their patients up for very long.”
As Dr. Grant discussed, ample research has demonstrated the potential anticancer effects of regional anesthesia. For instance, regional approaches have been shown to reduce the immune-modulating stress response of surgery by preventing noxious afferent input from reaching the central nervous system. Furthermore, regional techniques minimize opioid use and volatile anesthetic exposure, both of which have been shown to impair immune responses. Animal studies have also shown that regional anesthesia is an independent factor in reducing metastatic burden in animals exposed to breast adenocarcinoma.
Treatment Groups Followed 5 Years or More
Dr. Grant and his colleagues examined the records of 1,083 patients undergoing total unilateral or bilateral mastectomies for breast cancer at their institution; patients were only included if they had at least five years of follow-up. The investigators compared a host of information, including patient demographics, tumor characteristics, anesthetic method, treatment modality, disease recurrence rate and mortality.
The patients were divided into three groups based on anesthetic technique: volatile anesthetic without regional analgesia (n=648), volatile anesthetic plus paravertebral block (n=141), and monitored anesthesia care using propofol infusion with paravertebral block (n=294).
“It’s important to note that the propofol–paravertebral group is not opioid-free,” Dr. Grant told Anesthesiology News. “We still need some painkiller afterward, and they often get 50 mcg of fentanyl for block placement.”
Dr. Grant also explained that preliminary univariate analysis revealed some marked differences between patient groups. “It was interesting because our propofol–paravertebral group had more stage III or IV tumors than did the other groups, and also had more lymph node–positive tumors. So when you look at our initial data, you would imagine that the propofol–paravertebral patients should have a higher chance of recurrence.”
However, that was not the case. As Dr. Grant reported at the 2018 annual meeting of the American Society of Anesthesiologists (abstract A4299), paravertebral block with propofol was found to improve cancer recurrence rate compared with general anesthesia alone (odds ratio [OR], 0.55; 95% CI, 0.38-0.80; P=0.0019). Paravertebral block with propofol also proved superior to general anesthesia plus the block (OR, 0.48; 95% CI, 0.29-0.79; P=0.0041).
Patients who received the paravertebral block with propofol also benefited in terms of mortality, which was significantly lower than among patients receiving general anesthesia alone (OR, 0.49; 95% CI, 0.35-0.69; P<0.0001). However, there was no significant mortality benefit when the two groups that received the paravertebral block were compared.
In multivariate analysis, age was identified as an independent risk factor for mortality.
As Dr. Grant discussed, the techniques used in the paravertebral block with propofol patients may have played a role in the lower cancer rates in this study. “We use a very high concentration of local anesthetic in our block,” he said. “We also combined the block with propofol, which on its own has been shown to have benefits in terms of cancer recurrence compared to volatile anesthetic.
“I think that makes a difference at the time of surgery, when there can be marked tumor spread through the vascular system,” Dr. Grant said. “Normally, the vascular system is a very hostile environment for cancer cells. Giving people volatile anesthetics and opioids makes that environment a lot friendlier for those cells to spread. But high-dose local anesthetic is systemically absorbed, which makes it much more difficult for tumor cells to metastasize.”
Given these findings, the investigators believe the paravertebral block with propofol approach should be the anesthetic method of choice for women undergoing mastectomy. “The question is this: can we afford to not use this approach?” Dr. Grant asked. “What would you want if it was your wife, mother or sister?”
Although mastering this technique may once have been challenging, it is far simpler in the age of ultrasound guidance, he noted. “If you’re determined to learn the paravertebral block, it’s certainly something that can be taught to any practitioner, and the complication rate is extremely low.”
Nevertheless, the researchers recognized the limitations of their retrospective trial and await the results of prospective randomized trials on the topic. “In the meantime, this is a really strong and powerful indicator,” Dr. Grant said. “I really think there’s a signal here that what we do during cancer anesthesia can make a difference.”
Edward R. Mariano, MD, MAS, congratulated the investigators on completing a study that he said has important public health applications. “Dr. Grant and his colleagues have shown us that not all anesthetics are equal, and anesthesiologists and surgeons need to think about the downstream effects that their immediate perioperative choices have on patients’ long-term outcomes,” said Dr. Mariano, the chief of the Anesthesiology and Perioperative Care Service and associate chief of staff for Inpatient Surgical Services at the VA Palo Alto Health Care System, and a professor of anesthesiology, perioperative and pain medicine at Stanford University School of Medicine in Palo Alto, Calif.
“While the literature on anesthetic effects on cancer recurrence and survival is fraught with controversy, choosing an anesthetic approach that maximally preserves cancer patients’ innate immunity has biological plausibility and may have real outcome benefits,” Dr. Mariano said. “More importantly, why not?”
Yet as Dr. Mariano explained, the study’s encouraging findings need to be considered in context. “Dr. Grant and his colleagues have extensive experience with advanced regional anesthesia and an environment at their institution that supports collaborative development of clinical pathways,” he said. “What about anesthesiologists in other practice settings who do not have advanced regional anesthesia training? What can they offer their patients?
“In my opinion, it is important to provide anesthesiologists, surgeons and patients with potential alternatives in case ‘Plan A’ is not feasible,” Dr. Mariano said. “Some alternatives to paravertebral block—erector spinae plane, retrolaminar, midpoint transverse process to pleura—now exist that may decrease opioid exposure and required depth of anesthesia for surgery.
“While perhaps not sufficient for surgical anesthesia alone, these interfascial plane blocks when combined with total intravenous anesthesia may allow more patients to have access to regional analgesia and its potential benefits, as presented by Dr. Grant and colleagues.”