Dr. Kashyap,

After years of both researching and treating patients with severe sepsis and septic shock, this is the first I have heard of intentionally delaying fluid resuscitation in this patient population (if I understand your question correctly). I am aware that delays in the recognition of the syndrome may cause subsequent downstream delays in timely therapy, but had not heard of intentionally delaying fluid administration. Current recommendations from the Society of Critical Care Medicine advise early recognition and initiation of goal-directed therapy. Please keep us informed of novel therapeutic options, as this population represents a significant source of morbidity, mortality, and resource allocation. Thank you

Surviving Sepsis Guidelines Updated: Preview from SCCM Meeting

http://pulmccm.org/2012/critical-care-review/surviving-sepsis-guidelines-updated-at-sccm-meeting/

Dear Rahul,

You have to hope and pray that it is for a given patient very much like what you would do if the patient is seen in ER. However, even 30 min may be too late for other patients. I recall a family where one child had Meningococcal sepsis and was on the intensive care unit and survived after having been brought to ER in shock and we there were at least 5-6 hours when she was confused before falling asleep and another 3 hours before we saw the patient. Patient recovered within a week. On the day, we gave the good news to the mother that we will be moving the child from the ICU to a regular floor, another disaster happened. The mother was walking home with her other child and while crossing the street in the front of the hospital, that healthy child went into a shock and died within an hour despite all efforts. I remember the case well because I was at that time doing my ICU rotation as a resident.

In scientific terms, it all depends on what kind of a septic shock you are dealing with and that will of course depend on the host. If you have an adult with an otherwise healthy immune system, it may be too late because of the severity of the immune reaction that involves not only TLR mechanisms but also the participation of multiple pathways of severe infllammation. The capillary damage and the rate of third spacing may be so fast that fluid resuscitation will simply not work. But if you have an immunocompromised person with lets say leukemia and heavy chemotherapy and severe neutropenia, you may have a little more time because the inflammatory response elements are the chemoresistant innate immune response cells.

And of course you need to look at this in the context of the vasculature. How good are the capillary junctions. How good was the heart and lung function. How many organs are in dysfunction already when you start your intervention.

The take home message: 1. Act and remember, as our ICU attending during my residency would always tell us: "Detail kills". You have to do what you have to do fast and know that you may never be fast enough. 2. Keep your hope and remember pessimism is not something that will help your patient. 3. Remember: Septic shock # Septic shock. The picture varies from patient to patient.

@ Dr. Morre, No my question if not for delaying the treament, infact giving it sooner than recommended.

@ Dr. Uckun - great story, thanks for sharing, I agree that "You have to do what you have to do fast " and "pessimism is not something that will help your patient".

Dr. Kashyap,

Understood and agree. As we know, septic shock still carries a roughly 50% mortality rate while the case-fatality rates are slowly improving. We are doing a better job treating the disease... when we diagnose it... historically the issue has been the early recognition of the syndrome (most people don't miss the shock phase) severe sepsis. Our institution has instituted a "Sepsis Protocol" in our electronic medical record that the triage nurses in the emergency department can initiate when a patient presents with SIRS criteria in the setting of "suspected infection". This protocol consists of crystalloid resuscitation, a complete laboratory panel, cultures, notification of the senior provider, and potentially early antimicrobial therapy initiation. Our goal is to mitigate the delay in appropriate therapy waiting for definitive diagnosis of an infectious source. SIRS criteria and a strong clinical suspicion are all that are needed for the early initiation of empiric therapy (e.g. crystalloids).

Thank you for your clarification.

Dr. Uckun,

You bring up a good point that is not commonly addressed...severe sepsis and subsequent septic shock can be very individualized entities... especially as our understanding of TLR (and others) increases and the individual variances possible in the inflammatory cascade set forth by the mediators of inflammation.

Example, we recently had a 42 year old, otherwise healthy male present with acute appendicitis...non perforated...with symptoms less than 18 hours. This individual progressed through severe sepsis within roughly 2 hours waiting for the operating room and required vasopressor therapy prior to his uncomplicated laparascopic appendectomy. A thorough work-up was performed which did not elicit additional diagnoses nor confounders and he demonstrated rapid improvement after removal of the offending organ. My point here is, that the staff "denied" his degree of illness based on the fact that it was "only appendicitis... without perforation"... forgetting that it is not the amount of pus, bacteremia (if at all), or other more overt findings that predict the degree of the septic episode but rather the individual's inflammatory response to the insult...which can be quite variable.

if I didn' understand in a wrong way you question, I think that a cutoffs value for the time of resuscitation can't be placed in the settings of sepsis, because the redistribution phenomena is a important factor in the pathophysiology of the disease. it's clear for us, that the first approach to this kind of patients should be aaggressive for support the organism in the ebb phase of the shock, but this first approach and achieve the first goals ofor the EDT couldn't be enough and this patients need a bedside assessment and a lot of fluids for a correct resuscitation until the endothelial damage improve a little bit

The 6th hour is the upper cutoff. There is no lower cutoff, you could give fluid resuscitation as soon as identified and antibiotics right after bacterial samples are done . I tend to consider the 6th hour the time to vassopressor.

Once again time seems important in order to avoid hypotensive states. Hypotension mantained in time should be promptly resolved with agressive measures such as fluid resuscitation and vasopressor support if patient is not responsive. Every second of hypotension increases organ disfunction.

Check out our publication in CHEST 2 years ago -

Lee, S. J., Ramar, K., Park, J. G., Gajic, O., Li, G., & Kashyap, R. (2014). Increased fluid administration in the first three hours of sepsis resuscitation is associated with reduced mortality: A retrospective cohort study. Chest, 146(4), 908-915. DOI: 10.1378/chest.13-2702

http://www.sciencedirect.com/science/article/pii/S001236921533172X