Whole blood lactate kinetics in patients undergoing quantitative resuscitation for septic shock

Introduction We sought to compare the association of whole blood lactate kinetics with survival in patients with septic shock undergoing early quantitative resuscitation. Methods Preplanned analysis of a multicenter emergency department (ED)-based randomized control trial of early sepsis resuscitation targeting three physiological variables: central venous pressure, mean arterial pressure, and either central venous oxygen saturation or lactate clearance. Inclusion criteria: suspected infection, two or more systemic inflammatory response syndrome criteria, and either SBP 4 mmol/l. All patients had a lactate measured initially and subsequently at two hours. Normalization of lactate was defined as a lactate decline to 2.0 mmol/l was seen in 187/272 (69%), and 68/187 (36%) patients normalized their lactate. Overall mortality was 19.7%. AUCs for initial lactate, relative lactate clearance, and absolute lactate clearance were 0.70, 0.69, and 0.58, respectively. Lactate normalization best predicted survival (OR = 6.1, 95% CI = 2.2 to 21), followed by lactate clearance of 50% (OR = 4.3, 95% CI = 1.8 to 10.3), initial lactate of <2 mmol/l (OR = 3.4, 95% CI = 1.5 to 7.8), and initial lactate <4 mmol/l (OR = 2.3, 95% CI = 1.3 to 4.3), with lactate clearance of 10% not reaching significance (OR = 2.3, 95% CI = 0.96 to 5.6). Conclusions In ED sepsis patients undergoing early quantitative resuscitation, normalization of serum lactate during resuscitation was more strongly associated with survival than any absolute value or absolute/ relative change in lactate. Further studies should address whether strategies targeting lactate normalization leads to improved outcomes

The Explanatory Value of Abstracting Away from Idiosyncratic and Messy Detail

Some explanations are relatively abstract: they abstract away from the idiosyncratic or messy details of the case in hand. The received wisdom in philosophy is that this is a virtue for any explanation to possess. I argue that the apparent consensus on this point is illusory. When philosophers make this claim, they differ on which of four alternative varieties of abstractness they have in mind. What's more, for each variety of abstractness there are several alternative reasons to think that the variety of abstractness in question is a virtue. I identify the most promising reasons, and dismiss some others. The paper concludes by relating this discussion to the idea that explanations in biology, psychology and social science cannot be replaced by relatively micro explanations without loss of understanding.This work has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no 284123.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s11098-015-0554-