Hi everyone,
For a double dose of learning, today's extra POTD comes at the request of our wonderful PEM attending Dr. Hector Vazquez: should we be using etomidate in rapid sequence intubation (RSI) for septic pediatric patients?
Short answer? No. Long answer? It's complicated, but still no.
Etomidate's theorized effect on adrenal insufficiency = etomidate BAD
Etomidate is a bread-and-butter induction agent for us during intubation in the ED, often utilized for its hemodynamic stability and fast onset of action. However, the story started to really turn on etomidate in 2011 and 2012 when two systematic reviews and meta-analyses demonstrated that etomidate was associated with adrenal insufficiency and increased mortality in septic patients (Albert, Ariyan, & Rather, 2011; Chan, Mitchell, & Shorr, 2012). Why is this adrenal insufficiency thing such a big deal, anyways? It's because cortisol, our body's glucocorticoid that is produced by the adrenal gland, is absolutely vital during critical illness such as sepsis. Cortisol both helps maintain vascular responsiveness (good for blood pressure control in sepsis!) and has anti-inflammatory effects (good for fighting infection in sepsis!). The annoying part is that etomidate works through a cytochrome pathway that blocks conversion of cholesterol to cortisol. So more etomidate = less cortisol = adrenal insufficiency = not a good look.
Most of the adult literature on etomidate = etomidate EH BUT MOSTLY BAD
Honestly, like most of medicine, the data is controversial on the use of etomidate in sepsis in the adult literature. Even though the effect of etomidate on adrenal suppression is pretty well laid out, the question is if it is clinically significant and affects morbidity or mortality. A more recent systematic review and meta-analysis in 2021 reiterated the older meta-analyses findings, stating again an increase in adrenal suppression and mortality in septic patients (Albert & Sitaula, 2021). But, like most of medicine, many of the studies that were analyzed had some bias, some blinding blind spots, and varying definitions of all-cause mortality. A more recent RCT in 2023 even showed that there was no mortality difference between septic patients intubated with a single dose of etomidate vs. ketamine (Srivilaithon et al., 2023). All to say, the data isn't doing etomidate any favors when it comes to its use in septic adults, but it's not straight forward either. It's mostly bad, but we need better data, too. Journey with etomidate at your own risk.
Pediatric Sepsis Guidelines 2020 = etomidate BAD
Which brings us to peds patients. And make no mistake, the pediatric providers are stating it nice and clear for us: do not use etomidate in pediatric septic patients. In 2020, an expert panel released the holy grail for pediatric sepsis management, titled "Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis- Associated Organ Dysfunction in Children." Included in these guidelines are 77 evidence-based statements made up of 6 strong recommendations, 52 weak recommendations, and 9 best-practice statements.
And here's their recommendation regarding etomidate: We suggest not to use etomidate when intubating children with septic shock or other sepsis-associated organ dysfunction (weak recommendation, low quality of evidence). So no etomidate, but a weak recommendation... why do we even trust that? Well, pediatric patients just simply don't get the same research funding and consideration that adult patients get. A lot of the recommendations thus are based off of scant data, poor data, or adult data. And with such low quality of evidence overall, they only can claim to have weak recommendations. With regards to this recommendation in particular, as of 2020, no RCTs exist in critically ill children comparing etomidate to another sedation agent. But the recommendation is going off of two observational studies that included children in their patient population and four adult RCTs. Is it the cleanest recommendation? Definitely not. But they made an educated decision and pediatric septic patients should not be getting etomidate for RSI based on this recommendation. Maybe try ketamine instead.
So what were the 6 strong recommendations then?
In children with septic shock, we recommend starting antimicrobial therapy as soon as possible, within 1 hour of recognition (strong recommendation, very low quality of evidence)
We recommend removal of intravascular access devices that are confirmed to be the source of sepsis or septic shock after other vascular access has been established and depending on the pathogen and the risks/benefits of a surgical procedure (strong recommendation, low quality of evidence)
In healthcare systems with no availability of intensive care and in the absence of hypotension, we recommend against bolus fluid administration while starting maintenance fluids (strong recommendation, high quality of evidence)
We recommend against using starches in the acute resuscitation of children with septic shock or other sepsis-associated organ dysfunction (strong recommendation, moderate quality of evidence)
We recommend against the routine use of inhaled nitrous oxide (iNO) in all children with sepsis-induced PARDS (strong recommendation, low quality of evidence)
We recommend against insulin therapy to maintain glucose target at or below 140mg/dL (7.8 mmol/L) (strong recommendation, moderate quality of evidence)
To me, it wasn't so interesting to see what was included as strong recommendations, but more to see what was not included. If it's not listed here, but is typically something you would expect to be doing for a septic patient, it is likely listed as a weak recommendation or a best-practice statement. Meaning, lots of things we don't have all the evidence for but we have all collectively decided to do them anyway.
Happy intubating,
Kelsey
Resources:
1) https://pubmed.ncbi.nlm.nih.gov/21373823/
2) https://pubmed.ncbi.nlm.nih.gov/22971586/
3) https://jtd.amegroups.org/article/view/5542/5525#B19
4) https://pubmed.ncbi.nlm.nih.gov/32912050/
5) https://www.acepnow.com/article/should-you-etomidate-me/2/