JOURNAL CLUB: THE FLUIDS DEBATE Veronica Ueckermann
INTRODUCTION The selection and use of resuscitation fluids should be based on physiological principles. However, historically, clinical practice has been determined largely by clinical preference, with marked regional variation. Not just TYPE of resus fluid that determines outcome, but the TIMING and DOSE
OPPOSING STUDIES Got colloids banned VISEP CHEST 6S Brought colloids back CRYSTMAS CRISTAL
VISEP STUDY
CRITICISMS OF VISEP Flawed methodology: Hyperoncotic starch (10%). Prolonged infusions 4 days, 70.4 ml/kg It is known that hyperoncotic colloids impair renal functions and cause renal damage, regardless of the type used ethically flawed
CHEST STUDY
CRITICISM OF CHEST The CHEST study was powered for a single primary endpoint mortality. The result shows clearly that starch solution does not increase mortality, compared to normal saline. More patients who were given HES were given RRT RR confidence interval included one (i.e. not statistically significant) Once data was adjusted for known covariates, the p-value was no longer stastistically significant! Abstract: However, despite a lower overall rate of acute kidney injury, more patients who received resuscitation with HES were given renal replacement therapy
6S STUDY
CRITICISMS OF 6S Study not designed to investigate the secondary endpoint of renal injury: No criteria to initate RRT at discretion of staff in 32 intensive care units RIFLE criteria in fact favour starch group Number of days on dialysis same in both groups Enrollment AFTER resuscitation: Normal values lactate, central venous oxygen saturation at enrolment. Excessive ICU fluid administration: despite adequate resuscitation 4.5 litres of study fluid administered on day 1 and the subsequent 3 days accounts for high mortality in both groups!
FURTHER CONCERNS All 3 studies commenced after resuscitation phase CHEST enrolled on average 11hrs post ICU admission Absence of hypovolemia. In fact majority of the pts studied had already received colloids before randomisation in VISEP, 6S and CHEST! Duration > 24 hours MAINTENANCE with colloids! The largest volume of colloid (80%) administration occurs in trauma and peri-operatively. Yet, the meta-analysis excluded all but one publication in this area. Recent trauma studies suggest that collids is beneficial in resuscitation of trauma patients. FIRST trial saline vs voluven in penetrating trauma Hypotension after spinal anaesthesia: proven benefit colloids, crystalloid preloading ineffective and no longer used. Especially in patients at risk pulmonary oedema (pre-eclampsia)
FURTHER CONCERNS Administration of collids in presence of normal or increased plasma volume damages endothelial glycocalyx with resulatant transudation into the interstitium and worsening coagulopathy. Albumin may be the answer simply too expensive. Remember saline is the way to go for TBI (SAFE trial) Use of blood products as a substitute, in patients without transfusion indications is unsound, taking into account biological risks. Extrapolation from one context to another is DANGEROUS! The designs of these studies ignore basic physiological principles was the problem the colloids or the protocols?
ALL WE REALLY LEARN FROM THESE STUDIES Voluven may cause renal harm in elderly, critically ill patients with sepsis. NO evidence that it should be witheld from non-septic patients who require intravascular volume replacement The taditional ratio of crystalloid to colloids is 1:1.4 not 3:1 traditionally taught
THE STUDY THAT BROUGHT COLLOIDS BACK JAMA. 2013; 310(17):1809-1817.
CRISTAL
CRISTAL
CRISTAL
THE GLYCOCALYX
WHAT WE KNOW ABOUT THE GLYCOCALYX Blood-body-barrier interface between body and blood Components Proteoglycans Glycosaminoglycans Glycoproteins Soluble proteins Functions Gatekeeper determines vascular parmeability and interaction with components of blood Mechanotransduction mechanical protection from shear stress Microenvironment receptor binding, local growth and repair, vasculoprotection
GLYCOCALYX Fluids affect glycocalyx differently (albumin>colloids>crystalloids) Fluid amount influences glycocalyx fx Acute hyperglycemia = loss of glycocalyx volume High LDL levels and high fat diet disrupts glycocalyx Hydrocortisone and ATIII prevent TNF- induced shedding of the glycocalyx Endotoxxemia degreades the pulmonary endothelial glycocalyx and results in neutrophil adhesion in ALI Sepsis and major abdominal surgery damage glycocalyx
THE IDEAL FLUID Produce preodictable and sustained increase in IV volume Chemical composition as close as possible to ECF Metabolised and completely excreted without accumulation in tissues Does not produce adverse metabolic or systemic effects Cost-effective Improves outcomes