PURPOSE:
The optimal strategy of fluid resuscitation in the early hours of severe sepsis and septic shock is controversial, with both an aggressive and conservative approach being recommended.
METHODS:
We used the 2013 Premier Hospital Discharge database to analyse the administration of fluids on the first ICU day, in 23,513 patients with severe sepsis and septic shock, who were admitted to an ICU from the emergency department. Day 1 fluid was grouped into categories 1 L wide, starting with 1–1.99 L up to >9 L, to examine the effect of day 1 fluids on patient mortality. We built binary response models for hospital mortality and the propensity for receiving more than 5 L of fluids on day 1, using patient age and acute conditions present on admission. Patients were grouped by the requirement for mechanical ventilation and the presence or absence of shock. We assessed trends in the difference between actual and expected mortality, in the low fluid range (1–5 L day 1 fluids) and the high fluid range (5 to >9 L day 1 fluids) categories, using weighted linear regression controlling for the effects of sample size and variation within the day 1 fluid category.
RESULTS:
Day 1 fluid administration averaged 4.4 L being lowest in the group with no mechanical ventilation and no shock (3.6 L) and highest (5.4 L) in the group receiving mechanical ventilation and in shock. The administration of day 1 fluids was remarkably consistent on the basis of hospital size, teaching status, rural/urban location, and region of the country. The hospital mortality in the entire cohort was 25.8%, with a mean ICU and hospital length of stay of 5.1 and 9.1 days, respectively. In the entire cohort, low volume resuscitation (1–4.99 L) was associated with a small but significant reduction in mortality, of -0.7% per litre (95% CI -1.0%, -0.4%; p = 0.02). However, in patients receiving high volume resuscitation (5 to >9 L), the mortality increased by 2.3% (95% CI 2.0, 2.5%; p = 0.0003) for each additional litre above 5 L. Total hospital cost increased by $999 for each litre of fluid above 5 L (adjusted R2 = 92.7%, p = 0.005).
CONCLUSIONS:
The mean amount of fluid administered to patients with severe sepsis and septic shock in the USA during the first ICU day is less than that recommended by the Surviving Sepsis Campaign guidelines. The administration of more than 5 L of fluid during the first ICU day is associated with a significantly increased risk of death and significantly higher hospital costs.
COMMENTARY:
This is the largest observational study published to date examining the relationship between Day 1 fluid administration in patients with sepsis and mortality. The strength of the study lies in the fact that it is representative of real-life practice in the USA. Secondly, complex statistical models were developed which allowed for the comparison between the actual mortality and predicted mortality for each patient and for the deciles of Day 1 fluid administration (see figure below).
This study (ONCE again) has demonstrated that a liberal initial approach to fluid administration is associated with an increase in death. Administration of greater than 5L fluid on Day 1 increased the risk of death. Equally important, lower volumes of fluid administration were associated with a small but statistically significant reduction in mortality (see Figure below). These findings STRONGLY contradict the Surviving Sepsis Campaign Guidelines which recommend “aggressive fluid resuscitation during the first 24 h”.
Paul Marik
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More fluids are the cause of Mortality or a marker of more gravity?
Wondered the same. Doesn’t mean the fluid is appropriate at the doses given, but this may be a case of “sicker patients tend to die more”
This is not correct… please review the paper. This is one of the few studies that corrects for severity of illness. Multiple analyses correcting for severity of illness including propensity matching demonstrates that more fluid results in greater risk of death. ..Period.
Do you really think we know enough about sepsis phenotypes to correct for severity of illness. My goodness the one size fits all SEP 1 definitions and the latestest Sepsis 3 (which is SOFA repackaged) were simply guessed by a fre guys in the 1990s. If we could reliably correct for severity of illness we wouldn’t be using guessed one-size-fits-all definitions from the 1990s.
However. I see the point but where were the academic voices a when we predicted all th is guessing would fail. You are complaining that guessed treatment doesn’t work. Where was the complaint a decade ago that guessed “true states” won’t eork?
If a physician or researcher consumes and teaches (for 25 yrs) a guessed one-size-fits-all definition he or she shouldn’t expect to be empowered not to follow when the guessors become bold enough to guess and mandate a one-size-fits-all treatment for those that meet that definition.
Passive sheep can complain when they are herded but to the shepards, empowered by the herds passivity and behind whom the sheep have so willingly traveled for so long, such complaints are simply noise in the wind.
It’s a little too late to climb up on the high horse.
To play devils advocate, the fluid dose could be +vely correlated with mortality since we tend to keep giving fluids to those who do not improve with an initial dose(s). Therefore these two variables may be surrogate markers for illness severity.
that said, giving fluids at doses that SSC recommends makes no physiological sense, and harm has been documebted elsewhere.
Agree, AND excellent review article by Scott on SEP-1 https://www.ncbi.nlm.nih.gov/pubmed/27908335 AND easy to criticize protocols AND hard to formulate meaningful, widely applicable measures. So, what should constitute a meaningful list of sepsis process measures? Thoughts on the ACEP CEDR measures https://www.acep.org/globalassets/cedr_pdfs/CEDR-Measures-CMS-PQRS-Reporting.pdf?
no COI to declare
all very interesting, Paul.
I do suggest that anyone that has an interest in “sepsis” consider looking at the feb , 2017 Emerg. Med Clinics of north america which was dedicated to this subject. I do believe it was all quite good, but especially interesting was Dr Weingart’s last chapter (am forgetting the co-author from Boston, sorry).
thank you , Paul, once again.
tom
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Wow, some of these numbers on fluid levels administered would mean that patients weighed 150-300kg. Not saying we don’t have these patients; (we do) but again; just suggesting that many medical interventions should be based on IBW- not actual body weight. Common sense (not so common in SSC bundles) and experience teaches bariatrically challenged folks are already sicker, have poor compensatory mechanisms, and are difficult to resus from any situation. It’s a container problem , not volume.
Robin, you are correct. If one was so dumb as to actually follow the SSC guidelines it would make sense to use the IBW and not the actual body weight. This is particularly important in the USA were over 50% of the population are overweight Blood volume does not increase linearly with increasing body weight in obese subjects. This concept is supported by a recent publication which looked at this issue. …..
Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock. Taylor SR, et al. J.Crit Care 2017;43:7-12.
thanks for more good ammo. Keep fighting the good fight. People are starting to listen…..I’ll keep this one in my pocket as we have at least 1 or 2 a month over 150kg who have been drowned in 12-16 L. The struggle is real.
We see this as well.
Following a protocol instead of engaging the brain.
This is the pivotal lesson for all interested in sepsis, includfing the lay public. There are two types of thresholds Type I – guessed (WBC 12, bili 2, creat 2, HR 90, bands 10, platelets 100) Type II -discovered (HS Troponin 5) “Threshold Science” is a pathological science which originated in the late 70s and 8Os which uses type I (guessed) thresholds as “true states” (standards) in research.” As a pathological science (Langmuir) Threshold Science cannot generate reproducibly positive results. So, since Threshold Science is the present “science” of sepsis research, no reproducibly positive results have been generated in 25 yrs. Participating in the box of “Threshold Science” while arguing around it’s internal edges is futile. Indeed, such dissenters simply make the box look like real science. We can help your colleagues climb out of the box but first they have to recognize (and care) that they are in one. The repackaging of an old guessed set from the 90s (SOFA) means they are not climbing out. In summary: 1. You cannot replace discovery with guessing. 3. Exposing individual errors in Ptolemaic astronomy was a futile exercise, so exposing such errors in sepsis science is futile. 4. Only a man… Read more »