Anesthesia in the News
  • Can Perioperative Dexamethasone Lower Mortality Risk for Some Cancer Patients?

    Dexamethasone is widely and effectively used in the perioperative period for prophylaxis of postoperative nausea and vomiting (PONV), for pain management, and to facilitate early discharge after ambulatory surgery.  According to Dahl and colleagues, 32% to 45% of surgical patients will receive dexamethasone in the perioperative period as part of PONV prophylaxis or multi‐modal pain treatment.

    Now, new data also appears to associate dexamethasone with lower odds of mortality and higher odds of tumor-free survival in cancer patients who are not candidates for treatment with immune checkpoint inhibitors.

    The new analysis, which was published July 18 in the Annals of Surgery, included 30,561 adults who underwent surgery for cancer between 2005 and 2020.  The study was based on an analysis of hospital registry data from Beth Israel Deaconess Medical Center and Massachusetts General Hospital, both located in Boston, and 2 affiliated hospitals.

    2 hospital networks, >30k patients

    While previous studies hinted at dexamethasone’s protective properties in cancer, it has never before been shown on such a large scale.

    “Our analysis of more than 30,000 patients from two hospital networks adds to this discussion by its much larger sample size,” wrote the study authors who were led by Matthias Eikermann, MD, PhD, chair of anesthesiology at Montefiore Medical Center, New York.

    Earlier inroads

    Few studies have previously explored the potential connection between the reduced risk of mortality and corticosteroids and those studies have been small, so the connection has always been quite ambiguous the authors note.  For example, a 2018 study published in the  Annals of Surgical Oncology found that a single dose of dexamethasone administered to 117 patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy resulted in an improved median overall survival of 46 months vs. 22 months.

    Objectives and endpoints

    Dexamethasone is a strong synthetic member of the glucocorticoid class of steroid drugs that acts as an anti-inflammatory and immunosuppressant molecule (Cato, 1996), but its effects on cancer growth may depend on the specific cancer’s potential responsiveness to immunotherapy.  The investigators’ primary aim in this study was to determine if intraoperative administration of dexamethasone is associated with an improvement in 1-year overall survival in patients undergoing surgical resection of solid cancers.

    Due to the agent’s immunomodulatory effect, the second aim of the study was to determine whether these survival benefits were limited to patients with cancers that are not candidates for immune modulators (defined as those recommended for checkpoint inhibitor therapy based on the National Comprehensive Cancer Network guidelines).

    Finally, dexamethasone’s side effects include an increase in blood glucose levels following intraoperative administration, which could have a detrimental effect on surgical site infections (Cato, 1996).  Therefore, as a measure of the agent’s safety, the team evaluated the rates of postoperative hyperglycemia and surgical site infections.

    Impact and implications

    A total of 30,561 adult patients undergoing solid cancer resection between 2005 and 2020 were included in the study.  Of these, 11,666 (38.2%) received intraoperative dexamethasone (mean dose: 6.5±2.3 mg; 0.09±0.04 mg/kg).  A total of 980 (3.2%) patients died within 1 year of their operation, of whom 208 (1.8%) had received dexamethasone and 772 (4.1%) had not.

    The analysis showed that dexamethasone was associated with a -0.6% (95% confidence interval:  -1.1, -0.2, P=0.007) 1-year mortality risk reduction [adjusted odds ratio (ORadj): 0.79 (0.67, 0.94), P=0.009; hazard ratio=0.82 (0.69, 0.96), P=0.016] and higher odds of recurrence-free survival [ORadj:  1.28 (1.18, 1.39), P<0.001].

     

    The checkpoint inhibitor proviso

    The Eikermann et al. study sheds light on an important point that has previously received little attention:  the positive effects of intraoperative dexamethasone use appear to apply only to patients with cancers that do not respond to immune checkpoint inhibitors.

    “Our findings suggest differential effects of dexamethasone based on the cancer’s potential for guideline-based immunotherapy, [which provides] a basis for the explanation of diverging findings among previous studies,” the study authors explained.

    For patients with melanoma, bladder, lung, liver, and kidney cancer who were candidates for immune modulator therapy, “there was no association between intraoperative dexamethasone administration and one-year mortality (OR 1.13 [0.85, 1.50], p=0.40) or one-year recurrence-free survival (OR 1.01 [0.86,1.19], p=0.89),” which the authors attribute to dexamethasone’s ability to suppress T lymphocytes in these cancers which interfere with immune response.

    “These competing effects may explain that we found improved long-term survival only in patients with non-immunogenic cancers, but not with immunogenic cancers,” the authors wrote.

     

    Caveats on risks

    As mentioned, despite their ability to inhibit increased levels of inflammatory cytokines, there are risks associated with dexamethasone and corticosteroids in general, primarily hyperglycemia, which was documented in this study.  Although hyperglycemia has been associated with adverse clinical outcomes including surgical site infections, delayed wound healing, and increased hospital length of stay following cardiac surgery, general surgery, and in ICU patients, in this study dexamethasone administration did not increase deep surgical site infections within 30 days after oncologic surgery, “suggesting there is no increased risk of infection,” the investigators concluded

    Findings should ‘encourage and guide’

    According to the investigators, the results of this study “should encourage and guide the conduct and design of future RCTs investigating the effects of dexamethasone in patients undergoing cancer surgery.”

    Read more of your anesthesia-provider colleagues’ findings in “Association between Intraoperative Dexamethasone and Postoperative Mortality in Patients Undergoing Oncologic Surgery: A Multicentric Cohort Study,” at https://pubmed.ncbi.nlm.nih.gov/35837889/

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