Dr James Russell is a Professor of Medicine at UBC, Principal Investigator at UBC’s and St Paul’s Hospital’s Centre for Heart Lung Innovation, and founder and former head of UBC’s Critical Care Medicine division at St Paul’s Hospital. In 2019, he was ranked as the #1 expert in septic shock by the independent website Expertscape, based on his scientific publications over the past 10 years. Septic shock is a subset of sepsis, characterized by abnormally low blood pressure.
Along with antibiotics and fluid resuscitation, which are standard treatments for sepsis, treating septic shock also requires drugs that increase blood pressure (e.g., vasopressors). Yet controversy remains around the use of corticosteroids, a class of drugs that can decrease the need for vasopressors and interact with the body’s immune system to lessen the risk of injury to our vital organs - the heart, lungs, and kidneys. In some but not all studies, corticosteroids decrease death from septic shock. While these drugs have been used to treat septic shock for decades, it’s still unclear which patients benefit from this treatment.
Recently Dr Russell realized that clinicians who treat septic shock need guidance on the use of corticosteroids, after several very recent clinical trials of corticosteroids in septic shock found differing results. These clinical trials assessed whether corticosteroids are beneficial in decreasing the rate of death from septic shock - one found benefit but the other did not. Dr. Russell asked the lead investigators of those studies to explain why there was this dramatic difference in results.
They explained that these differences might be due to differences in the severity of sepsis in the patients taking part in the trials, or from interactions with other drugs given to these patients. In addition, they highlighted a key point: gene expression matters. Humans have about 20,000 genes, and each one is used (i.e., expressed) by the body in varying amounts. Researchers have shown that expression levels for some genes can differ between individuals suffering from sepsis, which in turn affects the individual’s response to corticosteroids in septic shock. More specifically, corticosteroids could be life-saving in one person with a beneficial genetic makeup (“genotype”) but of no help or even harmful in persons with other genotypes. Dr. Russell and his colleagues have done similar studies showing that unique proteins called cytokines also identify which patients respond best to corticosteroids.
While there’s still no clear answer yet regarding the role of corticosteroids in septic shock, these findings highlight the need for continued research to understand the complex biochemistry and genetics of sepsis. Before we can provide personalized testing for sepsis treatment, further studies by UBC’s sepsis group and others are still needed to identify which genotypes or proteins best predict an individual's response to different treatments, and evaluate whether using these genotypes or proteins to determine which patients need which treatments improves the alarmingly high rate of death for sepsis and septic shock.