Is this real life? Is this just fantasy? It’s Queen but could be The Matrix as well.
I still remember the good old days when I used to think guidelines were the fundamental truth in medicine. Oh boy! Was I really happy back then? I used to shout out loud: It’s in the guidelines, you illiterate dumbass! Level B! I loved the surviving sepsis campaign (SSC) guidelines! I knew every single paragraph by heart! I remember like it was today, hemoglobin around 10, activated protein C! Things got little more complicated when someone offered me the Blue Pill! I went from “I’m lovin’ it” to “I wanna kill those bastards!”. Ignorance is bliss.
Ok, you all might be thinking: “who the hell this motherfucker thinks he is?” Are you really going to dissect the guidelines written by the “Sepsis’ Avengers?” Well, no! I’m a D.C Comics kinda guy. Today, I’ll offer you the Blue Pill, bad jokes, and personal insults. Nothing more.
1- “At least 30 mL/kg of IV crystalloid fluid be given within the first 3 hours (strong recommendation, low quality of evidence).”
You won’t find any RCT comparing 30ml/kg vs. 20 or 50ml/kg. This recommendation is a well-educated guess at best. They say this rationale is supported by observational data and the protocol from PROCESS and Arise, while PROMISE said 2L (American friends, 2l is around 68oz).
So, if you take a closer look, the PROCESSS supplement you’ll find that the protocol for standard care was to give 500-1000ml of fluids. If the patient was not fluid replete or overloaded, they reached 2L. If the patient was still hypotensive and without signs of fluid overload/repletion, the doctors could go further. In the end, patients received around 30ml/kg during resuscitation phase.
Knowing all that, what our “Sepsis Avengers” did? Well, they skipped all the part you have to evaluate your patient and went straight to 30ml/kg. Examing a septic patient seems too complex for a guideline. “Let’s go with 30ml/kg; it’s easier”. They decided you don’t need to think if the patient is still hypotensive or if he is fluid overloaded. So, if your patient received 1L, is not hypotensive anymore and has signs of fluid overload you should keep going. If the median number is 30ml/kg, your patient must be right in that sweet median spot! Not 15, or maybe 40, 30 is the number.
I know, these guidelines are for those poor souls around the world in need of some chewable evidence. I’m from the north of Brazil (Amazon rainforest), I saw the battlefield. I could be a lamb and stay quiet, but I won’t! There’s a document called “users guide to the surviving sepsis campaign”(link), also available at their website, and there’s this flowchart:
To wrap it up: If your patients don’t have any problems with fluids, give’em 30ml/kg. And if they have any limitations to fluids? 30ml/kg! If they have bad lungs? Well, consider intubation and then give 30ml/kg! I don’t know if you believe in God, but if you do and He is septic, give Him 30ml/kg! That’s a JOKE! A flowchart with four options, all the SAME! The next SSC guidelines will probably come with a snorkel, and if the patient dies the recommendation will be to throw their ashes in the ocean!
2- “We suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion (weak recommendation, low quality of evidence).”
Recently our pal Fabio wrote some thoughts about lactate (here), and that’s all I have to say about that. One more thing. Reread this: “weak recommendation, low quality of evidence.” It’s like a shame certificate.
3- “We suggest empiric combination therapy (using at least two antibiotics of different antimicrobial classes) aimed at the most likely bacterial pathogen(s) for the initial management of septic shock (weak recommendation, low quality of evidence).”
In other words: doesn’t matter what your patients gave, give’em AT LEAST two different classes of antibiotics. Take pyelonephritis as an example. No ceftriaxone for him if he has septic shock! Give your patient some aminoglycoside too so that you can fry both of his kidneys!
The evidence here is based on observational data and some meta-analysis/meta-regression! The most cited source is that Kumar crap (A.K.A. The antibiotics lover). Let me quote him: “most studies were observational, using a variety of anti-infectives for varying durations in nonstandardized schedules”. Studies with 30 years of difference.
Now, imagine you have two patients with septic shock, both using ceftriaxone. One dies on the first day; the second one is still alive at day 3. Then, you decide to add another antibiotic for this guy. In an observational study the guy who lived long enough to receive another antibiotic is the guy in the “combined therapy group,” and the unlucky bastard who died in the first day is in the “monotherapy group.” A classic example of survivorship bias.
What about RCTs? There is only one good quality RCT in the market, with 600 patients which 71% had septic shock. The results: No difference!
But hold on. The cruelest part is yet to come. The rationale (if we can call that rational) is: “In light of the increasing frequency of pathogen resistance to antimicrobial agents in many parts of the world, the initial use of multidrug therapy is often required…” I won’t get into this today, but there is a fantastic article by Klompas addressing this issue. Do read.
4- “We suggest that procalcitonin levels can be used to support the discontinuation of empiric antibiotics in patients who initially appeared to have sepsis, but subsequently have limited clinical evidence of infection (weak recommendation, low quality of evidence).”
Ok, if I find out that what my patient has is probably a non-infectious I should measure procalcitonin levels in order to support my decision in withdrawing antibiotics? And if its pancreatitis? Procalcitonin might be elevated, and now I do what? Keep the antibiotic? These guys are crazy!
5- “We suggest using higher PEEP over lower PEEP in adult patients with sepsis-induced moderate to severe ARDS (weak recommendation, moderate quality of evidence).”
Nothing I would say here is louder than ALVEOLI, OLA AND EXPRESS.
6- “We suggest using recruitment maneuvers in adult patients with sepsis-induced, severe ARDS (weak recommendation, moderate quality of evidence).”
I know these guidelines were published before the ART trial. But even before the ART trial, there was no solid evidence supporting recruitment maneuvers. We discussed this here a long time ago (link).
There are still two other recommendations with no strong evidence behind them(monitoring gastric residual in patients with feeding intolerance or who are considered to be at high risk of aspiration and post-pyloric feeding tubes for this same patients), but I’ll save this for another post.
Yeah, I agree with you guys. This post is too depressing. Let’s change the VIBE! There are good feelings here also. We do not feed on the dark side of science. My honest congratulations to:
7- Inclusion of fluid responsiveness approach in shock management (although no matter what you’ll end up with 30ml/kg).
8- “We recommend that empiric antimicrobial therapy be narrowed once pathogen identification and sensitivities are established and/or adequate clinical improvement is noted (BPS).”
The 21st century was is against MDR bacterias and will be fought inside the hospital trenches. MDR bacteria is part of our daily living here in Brazil, and every day we have a truck parked outside our hospital full with meropenem to feed our KPC.
9- “We recommend against combination therapy for the routine treatment of neutropenic sepsis/bacteremia (strong recommendation, moderate quality of evidence).”
Yes my friends, we do have some good trials for this subgroup of patients. And the fun this is: in the most critical and susceptible group of patients, the combination therapy didn’t work.
10- “We recommend that RBC transfusion occur only when hemoglobin concentration decreases to < 7.0 g/dL in adults in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, or acute hemorrhage (strong recommendation, high quality of evidence).”
This makes me proud. Evidence-based medicine at last!
11- “We suggest against the use of IV immunoglobulins inpatients with sepsis or septic shock (weak recommendation, low quality of evidence).”
No evidence if we look at high-quality trials.
12- “We make no recommendation regarding the use of blood purification techniques.”
A lot of noise and no solid benefit until now. Marginal subgroup effects. That’s what they should say when there is no evidence.
13- ” We recommend that goals of care and prognosis be discussed with patients and families (BPS).”
Yeah, our patients are real people. Including goal of care discussion was the most climax of the guidelines.
In the end, this guideline really look like a guideline. I mean, you could light a fire with all the pages explaining about levels of recommendations, etc. For all the people I might have offended, and I know I did, sorry for the jokes. We’re still working on better ones.
Just remembering: we’re not here to go with the flow. We’re here to take you out of the matrix. We all know the philosophical goal of guidelines, and their role in battlefields, but we can’t say to people to do something just because the Avengers believe it’s good. By the way, if you are still reading this you are probably not prone to follow them without thinking. Stay away from drugs.
1- Rhodes A, Evans LE, Alhazzani W et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 Intensive Care Med. 2017; 43(3):304-377.
2- The ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock N Engl J Med. 2014; 370(18):1683-1693.
3- The ARISE Investigators and the ANZICS Clinical Trials Group. Goal-Directed Resuscitation for Patients with Early Septic Shock N Engl J Med. 2014; 371(16):1496-1506.
4- Mouncey PR, Osborn TM, Power GS et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock N Engl J Med. 2015; 372(14):1301-1311.
5- Kumar A, Safdar N, Kethireddy S, Chateau D. A survival benefit of combination antibiotic therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: A meta-analytic/meta-regression study Critical Care Medicine. 2010; 38(8):1651-1664.
6- Brunkhorst FM. Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe Sepsis JAMA. 2012; 307(22):2390-.
7- Klompas M. Monotherapy Is Adequate for Septic Shock Due to Gram-Negative Organisms Critical Care Medicine. 2017; 45(11):1930-1932.
8- The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome N Engl J Med. 2004; 351(4):327-336.
9- Kacmarek RM, Villar J, Sulemanji D et al. Open Lung Approach for the Acute Respiratory Distress Syndrome Critical Care Medicine. 2016; 44(1):32-42.
10- Mercat A, Richard JM, Vielle B et al. Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome JAMA. 2008; 299(6):646-.
11- Cavalcanti AB, Suzumura A, Laranjeira LN et al. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome JAMA. 2017; 318(14):1335-.