Treatment of septic patients : fluids, blood and timing of antibiotics

Background: Fluid therapy is an important component of the treatment of septic shock. The Surviving Sepsis Campaign recommends early fluid resuscitation with at least 30 ml/kg and there is no recommendation on when to stop giving fluids. Many studies have shown an association between fluid overload and morbidity and mortality. Clinicians base fluid prescription on variables that do not reflect fluid responsiveness. Aim: The overall intention was to explore what scientific support there is for the treatment of septic patients in terms of their fluid management and the timing of antibiotics and to investigate new tools that could help the clinician decide on the amount and timing of blood and other fluids in septic shock.

Overview of methods: See image in thesis pdf.

Summary of research results: The scientific support for how fluid management in patients with septic shock should be performed is poor. • It is safe to adopt a Hb threshold of 7 g/dl in septic ICU patients except in patients with preexisting cardiovascular disease for whom a transfusion threshold of 8 g/dl is suggested. • It is uncertain whether fluid overload is associated with mortality at a median fluid balance of 2.5 l on day three. • It has not been proven that protocolised haemodynamic management improves outcome. • It was possible to use the protocol based on a passive leg raising (PLR) test, but the recruitment rate was low. The weight gain was low in both the PLR and the control groups. • Female patients and patients with surgical sepsis were overrepresented in the group that received antibiotics after more than one hour in the emergency department. We could neither confirm nor exclude a survival benefit from early administration of antibiotics.

List of scientific papers

I. Lower versus higher hemoglobin threshold for transfusion in septic shock. Holst, L. B., Haase, N., Wetterslev, J., Wernerman, J., Guttormsen, A. B., Karlsson, S., Johansson, P. I., Aneman, A., Vang, M. L., Winding, R., Nebrich, L., Nibro, H. L., Rasmussen, B. S., Lauridsen, J. R., Nielsen, J. S., Oldner, A., Pettila, V., Cronhjort, M. B., Andersen, L. H., Pedersen, U. G., Reiter, N., Wiis, J., White, J. O., Russell, L., Thornberg, K. J., Hjortrup, P. B., Muller, R. G., Moller, M. H., Steensen, M., Tjader, I., Kilsand, K., Odeberg-Wernerman, S., Sjobo, B., Bundgaard, H., Thyo, M. A., Lodahl, D., Maerkedahl, R., Albeck, C., Illum, D., Kruse, M., Winkel, P., Perner, A., Triss Trial Group, Scandinavian Critical Care Trials Group. New England Journal of Medicine. 2014; 371(15): 1381-9.
https://doi.org/10.1056/NEJMoa1406617

II. Association between fluid balance and mortality in patients with septic shock: a post hoc analysis of the TRISS trial. Cronhjort M, Hjortrup PB, Holst LB, Joelsson-Alm E, Mårtensson J, Svensen C, Perner A. Acta Anaesthesiol Scand. 2016;60(7):925-33.
https://doi.org/10.1111/aas.12723

III. Impact of hemodynamic goal-directed resuscitation on mortality in adult critically ill patients: a systematic review and meta-analysis. Cronhjort M, Wall O, Nyberg E, Zeng R, Svensen C, Mårtensson J, Joelsson-Alm E. [Submitted]

IV. A passive leg raising test to reduce weight gain in patients with septic shock-a randomized clinical feasibility trial. Cronhjort M, Bergman M, Joelsson-Alm E, Divander MB, Jerkegren E, Balintescu A, Mårtensson J, Svensen C. [Submitted]

V. Timing of Antibiotic Treatment in a Swedish Cohort of Septic Intensive Care Patients. Cronhjort M, Rysz S, Sandström M, Svensen C, Mårtensson J, Bell M, Joelsson-Alm E. J Anesth Perioper Med. 2015; 2: 287-94.
https://doi.org/10.24015/JAPM.2015.0039