Adrenal function testing in patients with septic shock

INTRODUCTION: Adrenal failure (AF) is associated with increased mortality in septic patients. Nonetheless, there is no agreement regarding the best diagnostic criteria for AF. We compared the diagnosis of AF considering different baseline total cortisol cutoff values and Δmax values after low (1 μg) and high (249 μg) doses of corticotropin, we analyzed the impact of serum albumin on AF identification and we correlated laboratorial AF with norepinephrine removal. METHODS: A prospective noninterventional study was performed in an intensive care unit from May 2002 to May 2005, including septic shock patients over 18 years old without previous steroid usage. After measurement of serum albumin and baseline total cortisol, the patients were sequentially submitted to 1 μg and 249 μg corticotropin tests with a 60-minute interval between doses. Post-stimuli cortisol levels were drawn 60 minutes after each test (cortisol 60 and cortisol 120). The cortisol 60 and cortisol 120 values minus baseline were called Δmax(1 )and Δmax(249), respectively. Adrenal failure was defined as Δmax(249 )≤ 9 μg/dl or baseline cortisol ≤ 10 μg/dl. Other baseline cortisol cutoff values referred to as AF in other studies (≤15, ≤20, ≤25 and ≤34 μg/dl) were compared with Δmax(249 )≤ 9 μg/dl and serum albumin influence. Norepinephrine removal was compared with the baseline cortisol values and Δmax(249 )values. RESULTS: We enrolled 102 patients (43 male). AF was diagnosed in 22.5% (23/102). Patients with albumin ≤2.5 g/dl presented a lower baseline total cortisol level (15.5 μg/dl vs 22.4 μg/dl, P = 0.04) and a higher frequency of baseline cortisol ≤25 μg/dl (84% vs 58.3%, P = 0.05) than those with albumin > 2.5 g/dl. The Δmax(249 )levels and Δmax(249 )≤ 9, however, were not affected by serum albumin (14.5 μg/dl vs 18.8 μg/dl, P = 0.48 and 24% vs 25%, P = 1.0). Baseline cortisol ≤ 23.6 μg/dl was the most accurate diagnostic threshold to determine norepinephrine removal according to the receiver operating characteristic curve. CONCLUSION: AF was identified in 22.5% of the studied population. Since Δmax(249 )≤ 9 μg/dl results were not affected by serum albumin and since the baseline serum total cortisol varied directly with albumin levels, we propose that Δmax(249 )≤ 9 μg/dl, which means Δmax after high corticotropin dose may be a better option for AF diagnosis whenever measurement of free cortisol is not available. Baseline cortisol ≤23.6 μg/dl was the best value for predicting norepinephrine removal in patients without corticosteroid treatment

Effects of changes in arterial pressure on organ perfusion during septic shock

Septic shock is characterized by altered tissue perfusion associated with persistent arterial hypotension. Vasopressor therapy is generally required to restore organ perfusion but the optimal mean arterial pressure (MAP) that should be targeted is uncertain. The aim of this study was to assess the effects of increasing MAP using norepinephrine (NE) on hemodynamic and metabolic variables and on microvascular reactivity in patients with septic shock.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Microcirculatory assessment in daily clinical practice - not yet ready but not too far!

ABSTRACT Shock is characterized by an alteration in tissue perfusion that may lead to tissue hypoxia. Recent guidelines recommend aggressive and early resuscitation therapy, but mortality rate is still unacceptably high. Unfortunately, traditional clinical surrogates used to guide resuscitation therapy poorly correlate with microcirculatory blood flow, a key determinant of tissue perfusion. New techniques that directly assess microcirculatory perfusion at the bedside have emerged as a complement to traditional macrohemodynamic parameters. These techniques have been supported by several studies showing microcirculatory alterations in different clinical settings. In addition, these microcirculatory alterations are related with outcome and persist regardless of arterial pressure normalization, being a better predictor of organ dysfunction and mortality than global hemodynamic and laboratory parameters. These findings allowed the concept of “microcirculatory-goal directed therapy”, which is now in its preliminary phase, as the impact of many interventions still needs to be assessed. Finally, microcirculation assessment has also been explored in other medical fields such as perioperative, systemic arterial hypertension, heart failure, and hyperviscosity syndromes. In this review, we shortly present the characteristics of microcirculation and the main determinants of capillary blood flow, and we discuss advantages and limitations of some recently available techniques to evaluate microcirculation at the bedside, and how they could be useful for the general clinician in daily practice

Avaliação da microcirculação: uma nova arma no manejo da sepse?

A evolução para disfunção de múltiplos órgãos ainda é comum na sepse e está relacionada diretamente com a disfunção microcirculatória. Através de pesquisa nas bases de dados PubMed, empregando-se os unitermos microcirculação e sepse, vinte e seis artigos foram selecionados para esta revisão, bem como citações consideradas relevantes extraídas de artigos de revisão. Com o advento da técnica de imagem obtida através de polarização ortogonal, que permite a observação à beira do leito da microcirculação em pacientes críticos, é possível estabelecer uma relação entre disfunção microvascular e prognóstico, além de observar diretamente o efeito de diferentes intervenções terapêuticas. No entanto, a relação causal entre disfunção microcirculatória e prognóstico adverso na sepse, bem como os efeitos de terapias dirigidas para correção destas anormalidades microcirculatórias ainda precisam ser melhor definidos

Sublingual microcirculatory effects of enalaprilat in an ovine model of septic shock.

Severe sepsis is frequently associated with microcirculatory abnormalities despite seemingly adequate hemodynamic resuscitation. As increased serum angiotensin II levels may play a role in this dysfunction, we evaluated the microcirculatory effects of enalaprilat in an experimental model of septic shock. One hour after injection of 1.5 g/kg body weight of feces into the abdominal cavity, 16 adult female anesthetized, mechanically ventilated sheep were randomized to receive 2.5 mg enalaprilat or saline. When fluid-resistant hypotension (mean arterial pressure, <65 mmHg) developed, norepinephrine was given up to a maximal dose of 3 μg·kg(-1)·min(-1). The sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. A cutoff of 20 μm was used to differentiate small and large vessels. Experiments were pursued until the sheep's spontaneous death or for a maximum of 30 h. There were progressive and significant reductions in the proportion of small perfused vessels and in the microvascular flow index for small vessels (both P < 0.01 for trend) during shock and the first 2 h of norepinephrine infusion in the placebo group, which were prevented by the administration of enalaprilat. There were no differences between treated and placebo groups in global hemodynamic variables, time to shock or median survival time (21.8 [18.6-28.8] vs. 22.9 [21.8-30.0] h; P = 0.45). However, oxygen exchange was worse (PaO2/FiO2 ratio, 224 [128-297] vs. 332 [187-450]; P < 0.05), and creatinine concentrations increased more in the treated group (from 0.51 [0.42-0.75] to 1.19 [0.64-1.50] mg·dL(-1); P = 0.04) than in the control group (from 0.55 [0.45-0.62] to 0.78 [0.46-1.78] mg·dL(-1); P = 0.12), Enalaprilat therefore prevented the worsening of sublingual microcirculatory variables in this fluid-resuscitated, hyperdynamic model of septic shock, without significant effect on arterial pressure, but with a possible deleterious effect on renal and lung function.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt