Clinical Pearl 74: Why 30 ml/kg fluid bolus in Sepsis?

Recently Winters et al in a 2016 AAEM clinical practice guidelines concluded that “There is no difference in mortality between current usual care and the goal-directed approach recommended by current international guidelines for patients with severe sepsis and septic shock.”  This statement is based on the ARISE, PROMISE and PROCESS TRIALS.  As such more scientific evidence is being sought for the treatment of sepsis. The current recommendation per the “Surviving Sepsis Campaign” recommends the administration of 30 ml/kg crystalloid for hypotension or lactate > 4 mmol/L.  The Severe Sepsis 3-hour Resuscitation bundle recommends the 30 ml/kg fluid bolus therapy for the targeted guidelines are to have the CVP of ≥8 mm Hg, ScvO2 of ≥70 percent, and normalization of lactate. It is important to site there is no restriction for additional fluids but the minimal 30 ml/kg should be administered within 30-60 minutes of identification of septic patient.    There is no data to support the amount fluid resuscitation prospectively or retrospectively… only expert opinions.  Maitland et al studied pediatric patients presenting in shock in Sub-saharan Africa evaluating resuscitation with either saline or albumin compare to a no-bolus strategy in terms of all-cause mortality at 48 hours.  The Fluid Expansion as Supportive Therapy (FEAST) study published in 2011 and enrolled 3,141 Sub-Saharan children with severe febrile illness and impaired organ perfusion, and randomized them to receive either albumin, saline, or no volume resuscitation  At 48 hours, mortality was higher with albumin (10.6%) and saline (10.5%) as compared to no volume resuscitation (7.3%). Half of the participants had malaria and may not yield similar results as undifferentiated hypovolemic shock.

In the Journal of Critical Care, Hilton et al did a critique of fluid bolus in sepsis.  The author argue that 30 ml/kg has “weak physiologic support and limited experimental support.”  This interesting review for the ICU community questions why “nobody has ever challenged this dogma.”  This review cites many animal studies concluding that not even animal models show benefit for large volume fluid resuscitation. 

So if we do not have clear evidence of “help”  do we have evidence of “harm.”   The answer is yes.. in some models.  We know that fluid resuscitation boluses worsens outcome in penetrating torso trauma and positive fluid balances worsen outcome in Acute kidney injury, ARDS and recent colorectal surgery.  Also at cited above we know that NSS or Albumin in children with no significant cofounders has a 50 percent mortality increase. (FEAST STUDY)

In another 2017 study, Seethala et al evaluated the risk of developing ARDS in septic patients base on early fluid resuscitation.  2534 patients were evaluated using multivariate models.  6.2 percent of patient developed ARDS. In the first 6 hours in patients without shock, the amount of fluid resuscitation was associated with greater risk of developing ARDS 

But Why Is This? Several mechanisms exist regarding why Fluid Bolus Therapy worsens outcomes.  One model suggests rapid fluid infusion can also damage the endothelial glycocalyx leading to endothelialdisruption and organ dysfunction. Also expansion of blood volume in septic shock might increase distribution of harmful cytokines to end organs

In conclusion, of the 47 papers identified in the literature, we still have no support for 30 ml/kg.  In fact a better academic approach is to utilize repeat ultrasound evaluating the IVC, very early vasopressors, and frequent evaluations after several small bolus.  However in the true hypovolemic, hypotensive septic shock patient, fluid bolus therapy should still remain the mainstay of treatment until further randomized trials guide us.  

References:

1. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for  uid resuscitation in the intensive care unit. New England Journal of Medicine. 2004;350:2247-2256.
2. Choi PTL, Yip G, Quinonez LG, et al. Crystalloids vs. colloids in  fuid resuscitation: A systematic review. Critical Care Medicine. 1999;27:200-210.
3. Cook D, Guyatt G. Colloid use for  fluid resuscitation: Evidence and spin. Annals of Internal Medicine. 2001;135:205-208.
4. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: A systematic review of randomized trials. British Medical Journal. 1998;316:961-964.
5. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine. 2001;345:1368-1377.
6. Reinhart K, Kuhn HJ, Hartog C, et al. Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. Intensive Care Medicine. 2004;30:1572-1578.
7. Maitland K, et al. Mortality after fluid bolus in African children with severe infection. NEJM 2011. 364:2483-2495.
8. Wan L, Bellomo R, May CN: A comparison of 4% succinylated gelatin solution versus normal saline in stable normovolaemic sheep: global haemodynamic, regional blood fl ow and oxygen delivery effects. Anaesth Intensive Care 2007, 35:924-931.
9. Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators: A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 2008;12:74.
10. NHLBI ARDS Clinical Trials Network: Comparison of two fluid management strategies in acute lung injury. NEJM 2006, 354:2564-2575.
11. Durairaj L, Schmidt GA: Fluid therapy in resuscitated sepsis: less is more. Chest 2008, 133:252-263.
12. Bickell WH, Wall MJ Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL: Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injury. NEJM 1994;331:1105-1109.
13  Brandstrup B, Tønnesen H, Beier-Holgersen R et al. Danish Study Group on Perioperative Fluid Therapy: Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003, 238:641-648.
14. Burke-Gaffney A, Evans TW: Lest we forget the endothelial glycocalyx in sepsis. Crit Care 2012;16:121.
15.Woodcock TE, Woodcock TM: Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth 2012;108:384-394.

16. Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscita- tion in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011;39:259–265.
17. Hilton AK,  Bellomo . A critique of fluid bolus resuscitation inssevere sepsis. Critical Care 2012;16:1-5.
18.Brandt S, Regueira T, Bracht H, et al. Effect of fluid resuscitation on mortality and organ function in experimental sepsis models. Crit Care. 2009;13:186.
19.Durairaj L, Schmidt GA. Fluid therapy in resuscitated sepsis: less is more. Chest. 2008;133:252-63.
20.Glassford NJ, Eastwood GM, Bellomo R. Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data. Critical care. 18(6):696.
21.Madhusudan P, Tirupakuzhi Vijayaraghavan BK, Cove ME. Fluid resuscitation in sepsis: reexamining the paradigm. BioMed research international. 2014:984082..
22.Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ, Van Regenmortel N. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46:361-80

Clinical Pearl 72: GCSm: A New Standard Of Care In Assessing The Trauma Patient

The standard GCS score consists of visual, verbal and motor subscores. A randomized controlled trial published in Annals of Emergency Medicine in 2015 assessed the accuracy of EMS providers' GCS scoring as well as the improvement in the GCS score assessment with the use of a scoring aid. 178 completed the study. Overall, 41% gave a GCS score that matched the expert consensus score. GCS score was correct in 25% cases without the scoring aid. GCS was correct in 57% cases with the scoring aid. Differences in accuracy were most pronounced in scenarios with a correct GCS score of 12 or below. In summary, 60% of the EMS participants provided inaccurate GCS score estimates and the use of a GCS scoring aid improved accuracy of their score assessments.  So, instead of using a scoring aid why not just implement a simplified version of the GCS scoring system to minimize inaccuracy?

Another study published in Annals of Emergency Medicine in 2007 aimed to validate the Simplified Motor Score in a large heterogeneous trauma population. This was a secondary analysis of a prospectively maintained trauma registry with consecutive trauma patients who presented to a Level I trauma center from 1995 through 2004. Test performance of the GCS and the Simplified Motor Score relative to 4 clinically relevant traumatic brain injury outcomes (emergency intubation, clinically significant brain injury, neurosurgical intervention, and mortality) was evaluated with areas under the receiver operating characteristic curves (AUCs). The AUCs for the GCS and its components ranged from 0.76 to 0.92 across the 4 outcome measures. The AUCs for the Simplified Motor Score ranged from 0.71 to 0.89, and the relative differences from the GCS AUCs ranged from 3% to 7%, with a median difference of 5%. In this external validation study, the 3-point Simplified Motor Score (SMS) demonstrated similar test performance when compared with the 15-point GCS score and its components for the prediction of 4 clinically important traumatic brain injury outcomes. A second study of nearly 20,000 ICU trauma patients from 2011 found that the SMS acted equally to the GCS in predicting select trauma outcomes, offering it as an easier tool for pre-hospital providers to utilize in their trauma assessment.

In 2014, a study published in Journal of trauma and Acute Care Surgery, evaluated performance of the National Trauma Triage Protocol if GCm is substituted for the classic GCS score. GCSm score ≤ 5 increases specificity at the expense of sensitivity compared with GCS score ≤ 13.

In 2016, Doug Kupas and colleagues, in an evaluation of trauma outcomes from the Pennsylvania trauma data base, found that patients with a GCS- motor component less than 6 (“patient does not follow commands”) was equally effective in predicting select trauma outcomes (intubation, surgery, ICU admission, craniotomy, etc) as GCS, and again would serve as simple binary tool for EMS providers to utilize in their trauma assessment.

GCSm is superior to Total GCS.  Having a patient follow a motor command provides the easiest method to determine GCSm in a rapid accurate way.

References:

Brown JB, Forsythe RM, Stassen NA, Peitzman AB, Billiar TR, Sperry JL, Gestring ML. Evidence-based improvement of the National Trauma Triage Protocol: The Glasgow Coma Scale versus Glasgow Coma Scale Motor Subscale. J Trauma Acute Care Surg. 2014 Jul;77(1):95-102

Jaukoos JS, Gill MR, Rabon RE, Gravitz CS, Green SM. Validation of the Simplified Motor Score for the prediction of brain injury outcomes after trauma. Ann Emerg Meg. 2007 Jul;50(1):18-24.

Thompson DO, Hurtado TR, Liao MM, Byyny RL, Gravitz C, Haukoos JS. Validation of the simplified motor score in the out-of-hosptial setting for the preduction of outcomes after traumatic brain injury. Anne Amerg Med. 2011 Nov;58(5):417-25.

Feldman A, Hart KW, Lindsell CJ, McMullan JT. Randomized controlled trial of a scoring aid to improve Glasgow Coma Scale Scoring by emergency medical services proviers. Ann Emerg Med. 2015 Mar;65(3):325-329.e.2

Kuppas DF, Melnychuk EM, Young AJ. Glasgow Coma Scale Motor Component (“Patient Does Not Follow Commands”) Performs Similarly to Total Glasgow Coma Scale in Predicting Serve Injury In Trauma Patients. Ann Emerg Med. 2016 Dec.68(6):744-750.