Fluid Resuscitation in Septic Shock Patients With BMI Elevation (FRISSBE)

To explore the safety and feasibility of alternative fluid resuscitation strategies in obese patients with septic shock.

Early, goal-directed therapy with timely achievement of hemodynamic stability has been shown to clearly improve outcomes in patients with septic shock. Although Surviving Sepsis Campaign guidelines recommend a weight-based approach to initial fluid resuscitation (i.e. 30ml/kg),1 at present, there are no robust data to support whether dosing based on actual body weight or an alternative correction formula (ideal body weight, adjusted body weight) is superior. FRISSBE is a prospective, randomized, three-arm parallel-group pilot trial of alternative resuscitation strategies for obese patients with septic shock, looking at feasibility and safety of different weight-based approaches. Subject treatment assignment will not be blinded. Data will be collected and analyzed on an intent-to-treat basis. The study will enroll 60 subjects, with 20 subjects per treatment arm. Subjects will be randomized to receive one of three weight-based initial fluid resuscitation strategies - 30cc/kg ideal body weight (IBW), 30cc/kg adjusted body weight (AdjBW), or 30cc/kg actual body weight (ABW).

30cc/kg intravenous fluids based on the patients calculated ideal body weight will be administered when randomized to this arm Using Devine's formula. (men: 50kg + 2.3kg * (height(in) - 60); women: 45.5kg + 2.3kg * (height(in) - 60)

30cc/kg intravenous fluids based on the patients calculated adjusted body weight will be administered when randomized to this arm Calculated by the following formula: AdjBW = IBW + 0.4(ABW - IBW).

30cc/kg intravenous fluids based on the patients actual body weight will be administered when randomized to this arm Patients will receive an initial fluid bolus of 30 cc/kg of actual body weight

Proportion of patient in each group who experience death due to any cause during hospitalization up to 28 days

proportion of patients enrolled out of patients screened to randomized through completion of study, an average of 1 year

Inclusion Criteria: 18 years of age or older BMI > 30 suspected infection, and either: hypotension (a systolic blood pressure < 90mmHg) or blood lactate concentration > 4mmol/L Exclusion Criteria: Pregnant Primary diagnosis of acute cerebral vascular event Acute coronary syndrome Acute pulmonary edema Status asthmaticus Major cardiac arrhythmia Active gastrointestinal hemorrhage Seizures Drug overdose Burns or trauma Requirement for immediate surgery CD4<50/mm3 Do-not-resuscitate order status Transferred from another hospital

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552. doi: 10.1097/CCM.0000000000002255.

Wacharasint P, Boyd JH, Russell JA, Walley KR. One size does not fit all in severe infection: obesity alters outcome, susceptibility, treatment, and inflammatory response. Crit Care. 2013 Jun 20;17(3):R122. doi: 10.1186/cc12794.

Arabi YM, Dara SI, Tamim HM, Rishu AH, Bouchama A, Khedr MK, Feinstein D, Parrillo JE, Wood KE, Keenan SP, Zanotti S, Martinka G, Kumar A, Kumar A; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study. Crit Care. 2013 Apr 17;17(2):R72. doi: 10.1186/cc12680.

Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011 Feb;39(2):259-65. doi: 10.1097/CCM.0b013e3181feeb15.

Marik PE, Linde-Zwirble WT, Bittner EA, Sahatjian J, Hansell D. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med. 2017 May;43(5):625-632. doi: 10.1007/s00134-016-4675-y. Epub 2017 Jan 27.

Taylor SP, Karvetski CH, Templin MA, Heffner AC, Taylor BT. Initial fluid resuscitation following adjusted body weight dosing is associated with improved mortality in obese patients with suspected septic shock. J Crit Care. 2018 Feb;43:7-12. doi: 10.1016/j.jcrc.2017.08.025. Epub 2017 Aug 15.