The association between the presence and burden of periodic discharges and outcome in septic patients: an observational prospective study.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is frequent in septic patients. Electroencephalography (EEG) is very sensitive to detect early epileptic abnormalities, such as seizures and periodic discharges (PDs), and to quantify their duration (the so-called burden). However, the prevalence of these EEG abnormalities in septic patients, as well as their effect on morbidity and mortality, are still unclear. The aims of this study were to assess whether the presence of electrographic abnormalities (i.e. the absence of reactivity, the presence and burden of seizures and PDs) was associated with functional outcome and mortality in septic patients and whether these abnormalities were associated with sepsis-associated encephalopathy (SAE). METHODS: We prospectively included septic patients, without known chronic or acute intracranial disease or pre-existing acute encephalopathy, requiring ICU admission in a tertiary academic centre. Continuous EEG monitoring was started within 72 h after inclusion and performed for up to 7 days. A comprehensive assessment of consciousness and delirium was performed twice daily by a trained neuropsychologist. Primary endpoints were unfavourable functional outcome (UO, defined as a Glasgow Outcome Scale-Extended-GOSE-score < 5), and mortality collected at hospital discharge and secondary endpoint was the association of PDs with SAE. Mann-Whitney, Fisher's exact and χ2 tests were used to assess differences in variables between groups, as appropriate. Multivariable logistic regression analysis with in-hospital mortality, functional outcome, SAE or PDs as the dependent variables were performed. RESULTS: We included 92 patients. No seizures were identified. Nearly 25% of patients had PDs. The presence of PDs and PDs burden was associated with UO in univariate (n = 15 [41%], p = 0.005 and p = 0.008, respectively) and, for PDs presence, also in multivariate analysis after correcting for disease severity (OR 3.82, IC 95% [1.27-11.49], p = 0.02). The PDs burden negatively correlated with GOSE (Spearman's coefficient ρ = - 0.2, p = 0.047). The presence of PDs was also independently associated with SAE (OR 8.98 [1.11-72.8], p = 0.04). Reactivity was observed in the majority of patients and was associated with outcomes (p = 0.044 for both functional outcome and mortality). CONCLUSION: Our findings suggest that PDs and PDs burden are associated with SAE and might affect outcome in septic patients.

Correlation between heart rate variability and cerebral autoregulation in septic patients.

BACKGROUND: Heart rate variability (HRV) may provide an estimation of the autonomous nervous system (ANS) integrity in critically ill patients. Disturbances of cerebral autoregulation (CAR) may share common pathways of ANS dysfunction. AIM: To explore whether changes in HRV and CAR index correlate in critically ill septic patients. METHODS: Prospectively collected data on septic adult (> 18 years) patients admitted into a mixed Intensive Care between February 2016 and August 2019 with a recorded transcranial doppler CAR assessment. CAR was assessed calculating the Pearson's correlation coefficient (i.e. mean flow index, Mxa) between the left middle cerebral artery flow velocity (FV), insonated with a 2-MHz probe, and invasive blood pressure (BP) signal, both recorded simultaneously through a Doppler Box (DWL, Germany). MATLAB software was used for CAR assessment using a validated script; a Mxa >0.3 was considered as impaired CAR. HRV was assessed during the same time period using a specific software (Kubios HRV 3.2.0) and analyzed in both time-domain and frequency domain methods. Correlation between HRV-derived variables and Mxa were assessed using the Spearman's coefficient. RESULTS: A total of 141 septic patients was studied; median Mxa was 0.35 [0.13-0.60], with 77 (54.6 %) patients having an impaired CAR. Mxa had a significant although weak correlation with HRV time domain (SDNN, r = 0.17, p = 0.04; RMSSD, r = 0.18, p = 0.03; NN50, r = 0.23, p = 0.006; pNN50, r = 0.23, p = 0.007), frequency domain (FFT-HF, r = 0.21; p = 0.01; AR-HF, r = 0.19; p = 0.02), and non-linear domain (SD1, r = 0.18, p = 0.03) parameters. Impaired CAR patients had also all of these HRV-derived parameters higher than those with intact CAR. CONCLUSIONS: In this exploratory study, a potential association of ANS dysfunction and impaired CAR during sepsis was observed.

Cerebral Autoregulation Indices Are Not Interchangeable in Patients With Sepsis.

Introduction: Dynamic cerebral autoregulation (dCA) is frequently altered in patients with sepsis and may be associated with sepsis-associated brain dysfunction. However, the optimal index to quantify dCA in patients with sepsis is currently unknown. Objective: To assess the agreement between two validated dCA indices in patients with sepsis. Methods: Retrospective analysis of prospectively collected data in patients with sepsis; those with acute or chronic intracranial disease, arrhythmias, mechanical cardiac support, or history of supra-aortic vascular disease were excluded. Transcranial Doppler was performed on the right or left middle cerebral artery (MCA) with a 2-MHz probe, and MCA blood flow velocity (FV) and arterial pressure (BP) signals were simultaneously recorded. We calculated two indices of dCA: the mean flow index (Mxa), which is the Pearson correlation coefficient between BP and FV (MATLAB, MathWorks), and the autoregulation index (ARI), which is the transfer function analysis of spontaneous fluctuations in BP and FV (custom-written FORTRAN code). Impaired dCA was defined as Mxa >0.3 or ARI ≤ 4. The agreement between the two indices was assessed by Cohen's kappa coefficient. Results: We included 95 patients (age 64 ± 13 years old; male 74%); ARI was 4.38 [2.83-6.04] and Mxa was 0.32 [0.14-0.59], respectively. There was no correlation between ARI and Mxa (r = -0.08; p = 0.39). dCA was altered in 40 (42%) patients according to ARI and in 50 (53%) patients according to Mxa. ARI and Mxa were concordant in classifying 23 (24%) patients as having impaired dCA and 28 (29%) patients as having intact dCA. Cohen's kappa coefficient was 0.08, suggesting poor agreement. ARI was altered more frequently in patients on mechanical ventilation than others (27/52, 52% vs. 13/43, 30%, p = 0.04), whereas Mxa did not differ between those two groups. On the contrary, Mxa was altered more frequently in patients receiving sedatives than others (23/34, 68% vs. 27/61, 44%, p = 0.03), whereas ARI did not differ between these two groups. Conclusions: Agreement between ARI and Mxa in assessing dCA in patients with sepsis was poor. The identification of specific factors influencing the dCA analysis might lead to a better selection of the adequate cerebral autoregulation (CAR) index in critically ill patients with sepsis.

Automated Pupillometry as an Assessment Tool for Intracranial Hemodynamics in Septic Patients.

Impaired cerebral autoregulation (CA) may increase the risk of brain hypoperfusion in septic patients. Sepsis dysregulates the autonomic nervous system (ANS), potentially affecting CA. ANS function can be assessed through the pupillary light reflex (PLR). The aim of this prospective, observational study was to investigate the association between CA and PLR in adult septic patients. Transcranial Doppler was used to assess CA and calculate estimated cerebral perfusion pressure (eCPP) and intracranial pressure (eICP). An automated pupillometer (AP) was used to record Neurological Pupil Index (NPi), constriction (CV) and dilation (DV) velocities. The primary outcome was the relationship between AP-derived variables with CA; the secondary outcome was the association between AP-derived variables with eCPP and/or eICP. Among 40 included patients, 21 (53%) had impaired CA, 22 (55%) had low eCPP (<60 mmHg) and 15 (38%) had high eICP (>16 mmHg). DV was lower in patients with impaired CA compared to others; DV predicted impaired CA with area under the curve, AUROC= 0.78 [95% Confidence Interval, CI 0.63−0.94]; DV < 2.2 mm/s had sensitivity 85% and specificity 69% for impaired CA. Patients with low eCPP or high eICP had lower NPi values than others. NPi was correlated with eCPP (r = 0.77, p < 0.01) and eICP (r = −0.87, p < 0.01). Automated pupillometry may play a role to assess brain hemodynamics in septic patients.