Sergey Goodman

Adrenal function in sepsis: The retrospective Corticus cohort study

Objective:To refine the value of baseline and adrenocorticotropin hormone (ACTH)-stimulated cortisol levels in relation to mortality from severe sepsis or septic shock. Design:Retrospective multicenter cohort study. Setting:Twenty European intensive care units. Patients:Patients included 477 patients with severe sepsis and septic shock who had undergone an ACTH stimulation test on the day of the onset of severe sepsis. Interventions:None. Measurements and Main Results:Compared with survivors, nonsurvivors had higher baseline cortisol levels (29.5 ± 33.5 vs. 24.3 ± 16.5 &mgr;g/dL, p = .03) but similar peak cortisol values (37.6 ± 40.2 vs. 35.2 ± 22.9 &mgr;g/dL, p = .42). Thus, nonsurvivors had lower &Dgr;max (i.e., peak cortisol minus baseline cortisol) (6.4 ± 22.6 vs. 10.9 ± 12.9 &mgr;g/dL, p = .006). Patients with either baseline cortisol levels <15 &mgr;g/dL or a &Dgr;max ≤9 &mgr;g/dL had a likelihood ratio of dying of 1.26 (95% confidence interval, 1.11–1.44), a longer duration of shock, and a shorter survival time. Patients with a &Dgr;max ≤9 &mgr;g/dL but any baseline cortisol value had a likelihood ratio of dying of 1.38 (95% confidence interval, 1.18–1.61). Conclusions:Although delta cortisol and not basal cortisol level was associated with clinical outcome, further studies are still needed to optimize the diagnosis of adrenal insufficiency in critical illness. Etomidate influenced ACTH test results and was associated with a worse outcome.

Troponin elevation in severe sepsis and septic shock: The role of left ventricular diastolic dysfunction and right ventricular dilatation

Objective:Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Design:Prospective, analytic cohort study. Setting:Tertiary academic institute. Patients:A cohort of ICU patients with severe sepsis or septic shock. Interventions:Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Measurements and Main Results:Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e′-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and –2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s′-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e′-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e′-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Conclusions:Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Corticosteroids in Sepsis

The use of corticosteroids in severe sepsis and septic shock has been controversial for decades. The present chapter will review the potential benefits and detriments of the use of corticosteroids in sepsis, the use of corticosteroids in animal models of sepsis and, with particular emphasis, their use in humans with severe sepsis and septic shock.

Corticosteroid Treatment of Patients in Septic Shock

The use of steroids in septic shock patients has been controversial for decades [1, 2]. High-dose corticosteroids were standard therapy in the 1970s and 1980s [1, 2, 3, 4]. During the late 1980s and 1990s, however, the consensus was that corticosteroids should not be used in sepsis and septic shock after studies did not show an improved survival for patients treated with steroids [5, 6, 7, 8, 9]. Over the last decade, the recognition of inadequate adrenal corticosteroid production became more important as many critically ill patients were found to have relative adrenal insufficiency [10]. Studies in the late 1990s and early 2000s demonstrated hemodynamic benefits with lower doses of steroids for longer periods of time [11, 12, 13, 14, 15, 16]. Unfortunately, steroid use in critically ill patients has been associated with adverse affects [2] especially superinfections [2] and, more recently, critical illness polyneuromyopathy [17, 18]. In view of the ongoing controversy concerning the use of steroids in septic patients and recent studies on the subject, the current chapter attempts to review the topic, weighing the advantages and disadvantages of steroid treatment.