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Sepsis update: antibiotics and pressors

December 2023

WHILE THE NEWS may have been buried a bit during the pandemic, the Surviving Sepsis Campaign issued revised guidelines in 2021 that offer more than 90 recommendations on managing sepsis and septic shock.

“It’s a dense document, but don’t worry,” said Lekshmi Santhosh, MD, MA, an intensivist at the University of California, San Francisco, who spoke at UCSF’s hospital medicine conference this fall. “I read it so you don’t have to.”

This latest iteration reaffirmed a lot of what clinicians were already doing to treat sepsis. In the “Keep” column from previous guidelines, for instance, norepinephrine remains the first-line vasopressor.

“Once you start climbing up on norepinephrine doses, you want to add vasopressin.”


Lekshmi Santhosh, MD, MA

And early antibiotics are still key. “Antibiotics have a mortality benefit, particularly if you can get them on board in less than an hour,” Dr. Santhosh said. “I know we have to worry about stewardship, but if someone is in septic shock, you want that early, broad-spectrum therapy.”

Something else to do early: Address goals of care. “When patients are headed to the ICU with septic shock, it’s always a good time to recheck and reconfirm those goals.”

The guidelines did, however, highlight items that should be tossed. According to the new recommendations, no one should consider using vitamin C to treat sepsis. “There have been numerous trials,” said Dr. Santhosh. “That nail is in the coffin.”

You can also forget qSOFA, at least as a sepsis scoring tool. “We presented qSOFA a few years ago, but the new guidelines say it’s not valid because it’s not sensitive or specific enough.”

Starches and gelatins are also out, and most hospitals don’t even stock them anymore. “The hetastarches, the colloids—don’t use them,” Dr. Santhosh said.

As for what to start using, balanced crystalloids made the list. And—surprise!—clinicians should now start steroids in patients with septic shock.

Read about more about the new guidelines surrounding use of fluids and steroids in sepsis.

The latest on antibiotics
In terms of antibiotic timing, if shock is present, antibiotics should be administered immediately, ideally within one hour of recognition. In the absence of shock, give antibiotics, again ideally within an hour, for definite or probable sepsis.

If sepsis is possible, keep assessing for infectious vs. noninfectious causes of why the patient is ill—and administer antibiotics within three hours if your concern about infection persists.

“You can always de-escalate,” Dr. Santhosh pointed out. “If you’re not sure of the diagnosis, you have time to work up sepsis mimics. But the guidelines still want you to initiate earlier rather than later while you continue that workup.”

Recent studies have delivered other insights into antimicrobials and sepsis. The ACORN trial , for instance, published in JAMA in October 2023, looked at Zosyn (piperacillin-tazobactam) vs. cefepime.

“Numerous studies have shown that pip-tazo might actually raise patients’ risk of acute kidney injury,” she noted. “For the last couple of years, we’ve steered clear of Zosyn in sepsis in favor of cefepime.”

But the ACORN trial found no difference in the incidence of acute kidney injury between patients given pip-tazo and cefepime. “In fact,” said Dr. Santhosh, “the trial showed what many of us see in practice: that cefepime has a lot of neurotoxicity.” That makes it very hard, she added, “to disentangle in the septic patient who is altered and has toxic metabolic encephalopathy: Is it the sepsis or the cefepime?”

How have the results affected her practice? “This makes me think about any patient who’s already altered,” she said. “When I’m a little wary of using cefepime, I can feel more confident using a vancomycin/Zosyn combination—although I’ll still keep an eye on the creatinine.”

Other antibiotics news in 2023: The MERCY trial, published in June, looked to find any advantage to continuous IV antibiotics—this time with meropenem—vs. intermittent administration in patients with sepsis or septic shock. Study endpoints were mortality or the emergence of drug-resistant bacteria.

“This trial found no benefit to continuous IV antibiotics,” said Dr. Santhosh. “So you don’t need a special line for intermittent administration, you can keep on using your peripheral IV.”

One pearl Dr. Santhosh shared about pressors: Always “fill the tank” first with fluids and make sure the patient is volume replete before you start a vasopressor. Norepinephrine is the first-line vasopressor for patients with septic shock, and your target MAP is 65.

But “once you start climbing up on norepinephrine doses, you want to add vasopressin,” Dr. Santhosh said. “Studies find that the norepivaso combination actually helps prevent some AKI.” The best add-on option after that combination is epinephrine, “particularly if you have issues with impaired inotropy or impaired cardiac contractility.”

You almost never use dopamine in patients with septic shock unless the patient has bradycardia and a low risk of tachyarrhythmia. Dobutamine, meanwhile, is preferred for patients in cardiogenic or mixed shock.

Your final pressor option, phenylephrine, is “not a good drug for septic shock—with one important exception.” That exception is patients with septic shock who also are in A fib with RVR whose pressures are dropping.

A study published by Chest in 2022 compared the heart rate in just such patients with either phenylephrine or norepinephrine.

“The authors found that heart-rate lowering was much better in the phenylephrine group,” Dr. Santhosh said, adding that it made physiologic sense. Phenylephrine is a pure alpha vasoconstrictor, while norepinephrine has both alpha and beta. That affects cardiac contractility, which you don’t want.

“You don’t want that person to be tachying away even worse,” she said, adding that these results have changed her practice. “This is the rare situation where I’m going to reach for phenylephrine.”

Her last quick take on pressors: “The question always comes up when you’re on the floor and there’s no ICU bed for days: Are peripheral pressors OK?” Several smaller studies have shown that low-dose peripheral pressors, especially norepinephrine, are fine.

“Always, say, in the single digits, so less than 0.1,” she said. “Very low dose, as long as you have a closely monitored, large-bore 18- or 20 gauge IV, ideally not in the hand or wrist.”

A peripheral line in the antecubital fossa is safe for between 12 and 24 hours. After that, however, “you really should be looking at a central or PICC line.”

Read about more about the new guidelines surrounding use of fluids and steroids in sepsis.


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