Tiago Antônio Tonietto

Aldosterone secretion in patients with septic shock: a prospective study

OBJECTIVE To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

Elevated red blood cell distribution width at ICU discharge is associated with readmission to the intensive care unit

BACKGROUND Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. Our objective was to investigate the association between the RDW at ICU discharge and the risk of ICU readmission or unexpected death in the ward. METHODS A secondary analysis of prospectively collected data study was conducted including patients discharged alive from the ICU to the ward. The target variable was the RDW collected at ICU discharge. Elevated RDW was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Variables with a p-value <0.1 in the univariate analysis or with biological plausibility for the occurrence of the outcome were included in the Cox proportional hazards model for adjustment. RESULTS We included 813 patients. A total of 138 readmissions to the ICU and 44 unexpected deaths in the ward occurred. Elevated RDW at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward after multivariable adjustment (HR: 1.901; 95% CI 1.357-2.662). Other variables associated with this outcome included age, tracheostomy and mean corpuscular volume (MCV) at ICU discharge. Similar results were obtained after the exclusion of unexpected deaths in the ward (HR 1.940; CI 1.312-2.871) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580). CONCLUSIONS Elevated RDW at ICU discharge is independently associated with ICU readmission and in-hospital death.

Para: Hipotermia terapêutica após parada cardíaca: preditores de prognóstico

Determining the neurological prognosis of patients who have suffered cardiac arrest is extremely important because it allows the physician to inform the family about the life expectancy of their beloved relative, as well as to wisely plan for the allocation of available resources. We read with great interest the study performed by Leão et al., who assessed factors associated with worse neurological outcomes after cardiac arrest.(1) The study conducted by Leão et al. showed the ability of hypoxic-ischemic injuries viewed using magnetic resonance imaging of the brain to predict, in 72 hours, the prognosis of cardiac arrest survivors who had undergone therapeutic hypothermia (odds ratio OR 19.8; 95% confidence interval 95%CI: 1.7 229.6).(1) This result reinforces the recommendations by the American Heart Association in regard to magnetic resonance imaging of the brain for neurological prognosis evaluation after cardiac arrest.(2) The time from the return of spontaneous circulation until the target temperature was reached was also associated with the neurological prognosis. Patients who reached the target temperature more quickly presented worse neurological outcomes. However, we would like to highlight some important issues. First, the authors do not describe the initial temperature of the patients before they underwent therapeutic hypothermia. In addition, although hypothermia may reduce coronary perfusion, the fact that patients with more severe neurological damage were less reactive to low temperatures may make this finding a marker of worse prognosis and not necessarily its cause. The authors, as well as the editorial,(3) also state that such results corroborate the findings of the randomized clinical trial performed by Kim et al. However, it is necessary to emphasize that this study was conducted only in out-of-hospital cardiac arrest and that induction of pre-hospital hypothermia increased the time spent by the team on site, possibly delaying interventions, such as cardiac catheterization, and increasing the number of cardiac arrests during transport.(4) It is also important to note that the study population was heterogeneous (e.g., multiple initial cardiac arrest rhythms, distinct causes, in-hospital and out-of-hospital settings). These issues may have influenced patient outcomes. Moreover, the authors did not evaluate whether patients with findings suggestive of worse prognosis had any limitations with regard to treatment or withdrawal of support, leading to self-fulfilling prophecies. Lastly, the editorial(3) considers that the findings of Leão et al.(1) corroborate the maintenance of a temperature close to 36oC. However, it was not the aim of the study to evaluate the impact of temperature control on cardiac arrest survivors, Conflicts of interest: None.

Prophylactic haloperidol: too early to lose hope

Delirium is a very prevalent syndrome and an important independent predictor of negative outcome in patients in the intensive-care unit (ICU), but there is no proven pharmacological intervention to prevent or treat this disorder. Therefore, the study by Valerie J Page and colleagues, which provided an assessment of the use of haloperidol in the ICU setting, was needed. However, the results of this trial should not be classed as defi nitive because the study has some limitations. First, haloperidol was used as both a prophylaxis and treatment, and the number of patients with delirium at enrolment was not stated. We would expect that the dose needed to treat a patient with delirium would be higher than the prophylactic dose. Also, the criteria for stopping the drug should be reconsidered, since although patients might be 2 days free of delirium, they still could be at risk of developing delirium. Second, regarding the statistical analysis, the primary outcome was the number of delirium-free and comafree days in the first 14 days after randomisation, but patients who died before day 14 were recorded as having zero days free of delirium and coma, restricting the analysis to survivors, and correcting the incidence of the main outcome (delirium) according to the competing event (death). When analysing time-to-event data and competing outcomes, a technique known as cumulative incidence analysis can be used to assess the actual incidence of delirium. This type of analysis would have provided more accurate results in Page and colleagues’ study, and should be used in future trials that intend to address delirium incidence. Last, the study authors conclude that their results do not support the use of haloperidol in patients needing mechanical ventilation, irrespective of whether patients screen positive for delirium or are in a coma. They believe that haloperidol should be reserved for short-term management of acute agitation; however, we think it is too soon to come to this conclusion.