Variabilidade da frequência cardíaca como preditor de mortalidade na sepse

Abstract

Introduction: Sepsis is a severe medical condition with increasing prevalence and high mortality. The role of the autonomic nervous system in the pathophysiology of sepsis has been increasingly researched. The objective of this study is to evaluate the heart rate variability (HRV) as a predictor of mortality in septic patients through a cohort study and a systematic review. Methods: In the prospective cohort of patients diagnosed with sepsis, patient recruitment was carried out at ICU in a tertiary university hospital between March 2012 and February 2014. Clinical data and laboratory exams were collected at admission. Each patient underwent a 20-minute Holter and a 24-hour Holter on the first day of enrollment. The primary outcome was the 28-day all-cause mortality. In the systematic review of studies evaluating HRV as a predictor of death in patients with sepsis, the search for articles was performed by independent researchers in PubMed, LILACS and Cochrane, including papers in English, Portuguese or Spanish, indexed until August 20th, 2017 with at least 10 patients. Study quality was assessed by the Newcastle-Ottawa Scale. To analyze the results, we divided the articles between those who measured HRV for short-term recordings ( 1 hour), and those who did longterm recordings ( 24 hours). Results: In the cohort study, a total of 63 patients were included. Patients were categorized into nonsurvivor group (n = 16) or survivor group (n = 47) depending on this endpoint. Survivors were younger (48.6 years vs. 63.0 years), had better renal function and lower values in severity scores (APACHE II and SOFA) compared to nonsurvivors. In the 20-minute Holter, SDNN, TP, VLF, LF and LF/H of nonsurvivors were significantly lower than those of survivors (p 0.001, p = 0.003, p = 0.002, p = 0.006, p = 0.009 respectively). ROC curve of SDNN was built, showing area under the curve of 0.772 (0.638±0.906) for mortality prediction. The value of 17ms was chosen as the best SDNN cutoff point to discriminate survivors and nonsurvivors. In the Cox proportional regression, adjusted for SOFA score and for APACHE II, a SDNN 17ms was associated with a greater risk of death, with hazard ratios of 6.3 (1.4± 28.0; p = 0.015) and 5.5 (1.2±24.8; p = 0.027), respectively. The addition of the dichotomized SDNN to the SOFA model reduced AIC and increased the concordance statistic and the R2, indicating that predictive power of the SDNN + SOFA model is better than predictive power of SOFA only. In the systematic review, nine studies were included with a total of 536 patients. All of them were observational studies. Studies´ quality varied from 4 to 7 stars in NewcastleOttawa Scale. The mortality rate in studies ranged from 8 to 61%. Seven studies performed HRV analysis in short-term recordings. With the exception of one study that did not explain which group had the lowest results, all other studies showed reduction of several HRV parameters in the non-survivors in relation to the surviving septic patients. SDNN, TP, VLF, LF, LF/H, nLF, á1/á2 and r-MSSD of the non-survivor group were reduced in relation to the survivors in at least one study. Two studies found that SDNN is associated with mortality in sepsis, even after adjusting for possible confounding factors. Three studies performed HRV analysis using long-term recordings. Only one of these studies found difference between surviving and non-surviving groups, and even so, in only one HRV parameter: LogHF. Conclusions: Several HRV parameters are reduced in nonsurviving septic patients. In our cohort study, SDNN 17 ms appeared as a risk factor for death in septic patients, even after adjusting for severity scores. In the systematic review, SDNN seems to be independently associated with mortality in sepsis in two studies. These findings make SDNN emerge as the most useful HRV parameter to predict mortality in septic patients.