Conference Coverage

Septic shock: Innovative treatment options in the wings



Vitamin C, angiotensin-II, and methylene blue are emerging options on the cutting edge of refractory septic shock treatment that require more investigation, but nevertheless appear promising, Rishi Rattan, MD, said at the annual clinical congress of the American College of Surgeons.

Dr. Rishi Rattan  trauma and critical care surgeon with the Ryder Trauma Center at the University of Miami. Andrew Bowser/MDedge News

Dr. Rishi Rattan

Trials evaluating vitamin C in this setting have demonstrated a large mortality impact with an absence of side effects, according to Dr. Rattan, a trauma and critical care surgeon with the Ryder Trauma Center at the University of Miami.

“It’s something that I have decided to start early adopting, and many of my colleagues at University of Miami do as well,” Dr. Rattan said in a panel session on updates in septic shock. “We’re anecdotally so far at least seeing good results and are going to be excited to see what these ongoing trials show.”

As an antioxidant, vitamin C has anti-inflammatory properties that may possibly attenuate the overly exuberant inflammatory response seen in septic shock, Dr. Rattan said in his presentation.

The limited clinical data for vitamin C in refractory shock include three studies, of which two are randomized controlled trials, comprising a total of 146 patients, he added.

“I will admit an N of 146 is hardly practice-changing for most people,” Dr. Rattan said. “There’s still a significant and sustained large mortality effect for the use of vitamin C, with nearly no adverse effects.”

Pooled analysis of all three studies revealed a marked reduction in mortality with the use of vitamin C (odds ratio, 0.17, 95% confidence interval 0.07–0.40; P less than .001), according to a meta-analysis recently just published in Critical Care that Dr. Rattan referenced in his presentation (Critical Care 2018;22:258, DOI:10.1186/s13054-018-2191-x).

When taken in recommended dosages, vitamin C given with corticosteroids and thiamine is without known side effects, researcher Paul E. Marik wrote earlier this year in an editorial in Pharmacology & Therapeutics (2018;189[9]:63-70, DOI:10.1016/j.pharmthera.2018.04.007) noted Dr. Rattan, who said he uses the intravenous vitamin C, thiamine, and hydrocortisone protocol previously reported by Dr. Marik and colleagues.

There are 13 ongoing trials, including some prospective blinded, randomized trials, looking at the role of vitamin C in refractory shock, he added.

Angiotensin-II is another intervention that may be promising in refractory septic shock, Dr. Rattan told attendees, pointing to the 2017 publication of the ATHOS-3 trial in the New England Journal of Medicine (2017; 377:419-430,DOI: 10.1056/NEJMoa1704154) showing that treatment increased blood pressure in patients with vasodilatory shock not responding to conventional vasopressors at high doses.

Likewise, methylene blue has shown promise in septic shock, at least in some limited clinical investigations and anecdotally in patients not improving despite standard interventions. “I’ve been able to have a couple patients walk out of the hospital with the use of methylene blue,” Dr. Rattan said. “Again, the plural of ‘anecdote’ is not ‘data,’ but it’s something to consider for the early adopters.”

Dr. Rattan had no disclosures related to his presentation.

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