See the first part of this sepsis and shock update on antibiotics and pressors here.
Fluids: which to use?
As Dr. Santhosh explained, Medicare a few years ago threatened to come down hard on any clinician who wasn’t giving 30 cc/kg of IV fluids to every septic patient within the first two hours.
“There’s not a huge deleterious effect of normal saline vs. PlasmaLyte, except in extreme cases.”
Lekshmi Santhosh, MD, MA
“But they quickly realized that one size does not fit all in sepsis,” she pointed out. “We have patients with heart failure, liver failure, kidney failure or all of the above. You want to tailor your fluid regimen with repeated small boluses.”
When someone is hypotensive, you need to start fluid resuscitation. The 2021 Surviving Sepsis guidelines make it clear that crystalloids—PlasmaLyte or lactated ringers—are “much, much better than colloids. And resist any temptation to use albumin!”
Why are balanced crystalloids preferred over normal saline? Smaller studies have suggested that normal saline—because of the chloride in it—often triggers hyperchloremic metabolic acidosis. That in turn affects patients’ respiratory status.
But the BaSICS trial on fluid resuscitation published in JAMA in 2021 compared balanced crystalloids to normal saline in critically ill patients who needed IV fluids. The results: Balanced crystalloids offered no benefits over normal saline in terms of 90-day survival rates. (The PLUS trial published in the New England Journal of Medicine in 2022 affirmed BaSICS’ findings on PlasmaLyte vs. normal saline.)
In her own practice, Dr. Santhosh said she typically relies on PlasmaLyte. But according to these large trials, “there’s not a huge deleterious effect of normal saline vs. PlasmaLyte, except in extreme cases. If you’re relatively judicious, you won’t see those bad effects.”
Fluids: How fast and how much?
The BaSICS trial also featured a second arm that looked for mortality benefits with slow (333 ml/hr) resuscitation vs. fast (999 ml/hr). But researchers found no mortality differences between those two groups.
“This BaSICS trial reaffirmed what we were already doing,” said Dr. Santhosh. “When someone is hypotensive, I always teach: Just run those fluids in a bolus, wide open, and then reassess. Get patients pumped up quickly.”
As for a liberal vs. a restricted fluids strategy, the CLASSIC study, published in 2022, was another negative trial in terms of mortality benefit. However, “that trial didn’t find a huge separation between the liberal and the restrictive fluid groups in terms of fluid amounts, and that gave us pause,” Dr. Santhosh said.
This year’s CLOVERS trial likewise looked at liberal vs. restrictive fluids—and also found no mortality difference.
“But that study did see a good separation between the two groups in terms of the amount of fluids given,” she pointed out. At the same time, “we all see septic patients who are volume overloaded, especially when they come out of the ICU. They’ve gained so much body weight, so think twice about overloading patients upfront.” Also think about escalating early to pressors when patients aren’t responding to fluids.
So where do all these fluid recommendations land? “I told you to be judicious with boluses, particularly in all the hospital medicine patients with kidney, renal or heart failure,” said Dr. Santhosh.
And in the critical care community, “these trials are still ‘one size fits all.’ Instead, we should take a personalized approach to each patient. Start with fluids first, see if the patient in front of you is fluid-tolerant—and if they’re not, escalate to pressors.” For patients with heart or renal failure, you need smaller IV fluid doses of 250 ccs.
Dr. Santhosh did sound this note of caution about fluids: Beware the “lacto-bolo reflex.”
“When you see a lactate, don’t automatically click ‘reorder bolus,’ ” she said. “Instead, go and see the patient and think about why they may have an elevated lactate.” While you need to trend lactate out, “it can be persistently elevated at baseline in some patients with chronic liver or kidney disease.”
That’s also true for patients who’ve had a seizure or are in alcoholic withdrawal. “Don’t just reflexively give big fluids when you see that lactate,” she said. “Go and reassess how the patient is doing.”
Steroids: They’re back!
One important recommendation included in the revised guidelines: Start steroids for patients with septic shock, using IV hydrocortisone 200 mg/day, “especially when patients are on escalating doses of even one pressor.”
As for those with septic shock and sepsis-induced adrenal insufficiency, Dr. Santhosh noted that a “very well-done,” practice-changing study that appeared in 2023 in JAMA Internal Medicine looked at more than 8,000 patients in multiple ICUs across the country. The trial compared hydrocortisone alone to hydrocortisone plus fludrocortisone. The primary outcomes measured were hospital death or discharge to hospice.
“This is in patients who are already on pressors, that’s part of the inclusion criteria,” said Dr. Santhosh. “They found that the combination had a mortality benefit over hydrocortisone alone.”
How much of each? The study, she pointed out, “had very protocolized recommendations, which are the ones I use in my practice.” For hydrocortisone, “you’re aiming for 200 to 300 mg per day,” which she typically doses at 50 mg q 6. As for fludrocortisone, “a little goes a long way, so 0.1 mg per day.”
As for when to discontinue steroids, most protocols and studies say to use them for three days—but if patients get off pressors earlier, you could stop steroids sooner. Moreover, “you don’t need to taper. Just on or off.”
Phyllis Maguire is Executive Editor of Today’s Hospitalist.
ASKING AUDIENCE members to use their response keypads, Lekshmi Santhosh, MD, MA, a UCSF intensivist, at a hospital medicine conference this year, posed this question: How many of their home hospitals maintain a post-ICU clinic? Only 2% answered “yes.” That includes the post-ICU OPTIMAL clinic at UCSF, she said.
As she pointed out, many sepsis survivors are left with not only physical challenges, but mental and emotional ones as well.
“There are a lot of data that sepsis leads to long-term immunosuppression and immune disturbances,” Dr. Santhosh pointed out. “And a recent trial showed increases in long-term cancer risk.”
If you see patients recovering from sepsis either on the wards or in outpatient clinics, Dr. Santhosh urged physicians to ask about four domains: pulmonary issues, physical function, cognitive function and mental health. “Sometimes, these are very closely interrelated.”
Read about what to keep doing in sepsis care when it comes to antibiotics and pressors here.