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Evidence supporting the deleterious effects

fluid resuscitation


rather than low ScvO2 has been demonstrated to be an independ- ent predictor of death.96Three large randomized controlled trials (ProCESS, ARISE and PROMISE) have now demonstrated that ti- trating therapy to a ScvO2 > 70% does not improve outcome,8–10but rather increases the risk of organ dysfunction, length of ICU stay and increased use of resources and costs.10These observa- tions must lead to the conclusion that the original EGDT study

was not scientifically valid and that no aspect of this study should be used to guide the management of patients with severe sepsis and septic shock.39798

In addition to targeting a CVP greater than 8 mm Hg, the Sur- viving Sepsis Campaign guideline recommends ‘targeting resusci- tation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion’.7 This recommendation is based on the notion that an elevated lactate is a consequence of tissue hypoxia and inadequate oxygen delivery.95However, these asser- tions are likely wrong.99Hotchkiss and Karl100in a seminal re- view published over 20 yr ago, demonstrated that cellular hypoxia and bioenergetic failure does not occur in sepsis. It has

now been well established that epinephrine released as part of the stress response in patients with severe sepsis, stimulates Na+ K+-ATPase activity. Increased activity of Na+ K+ ATPase leads to increased lactate production under well-oxygenated conditions in various cells, including erythrocytes, vascular

smooth muscle, neurons, glia, and skeletal muscle.101 102While


Of aggressive

The harmful effects of aggressive fluid resuscitation on the out- come of sepsis are supported by experimental studies and data accumulated from clinical trials.109110Multiple clinical studies have demonstrated an independent association between an increasingly positive fluid balance and increased mortality in patient with sepsis.29111–120The most compelling data that fluid loading in sepsis is harmful, comes from the landmark ‘Fluid Expansion as Supportive Therapy (FEAST)’ study performed

in 3141 sub-Saharan children with severe sepsis.121In this rando-

mized study, aggressive fluid loading was associated with a sig- nificantly increased risk of death. After the Rivers’ Early Goal Directed Therapy trial,3which formed the basis for the concept of early aggressive fluid resuscitation, a number of EGDT studies have been published.48–10122An analysis of these studies de- monstrates a marked reduction in mortality over this time period (see Fig. 2). While all these studies emphasized the early use of appropriate antibiotics, the decline in the amount of fluids admi- nistered in the first 72 h is striking. Furthermore as illustrated in Fig. 3 there is a very strong correlation between the amount of

fluid administered (in first 6 h) and the target CVP. It should be noted that the CVP in the usual arm of both the ARISE (The Australasian Resuscitation in Sepsis Evaluation) and ProMISe (Protocolised Management in Sepsis) trials was greater than 10 mm Hg, being almost identical to the EGDT arm, and with





 


almost an identical amount of fluid being administered in the usual arm, as in the active EGDT arm in both studies.910Clini- cians seem compelled to give fluid when the CVP is less than 8 mm Hg; the only solution to this pervasive problem is to stop measuring the CVP.

 


Date: 2016-04-22; view: 594


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Fluid responsiveness and the haemodynamic effects of fluids in patients with sepsis | Resuscitation strategy
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