Microcirculatory Alterations in Critically Ill Patients with COVID-19-Associated Acute Respiratory Distress Syndrome.

BACKGROUND: Presently, a number of specific observations have been performed on microcirculatory function in a coronavirus disease-19 (COVID-19) setting. We hypothesized that, in the critically ill, endothelial dysfunction secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the subsequent inflammation and coagulopathy may lead to microcirculatory alterations, further exacerbated by the hypoxemic state. A dysfunctional microcirculation may represent the hidden motor underlying the development of COVID-19's clinical manifestations. METHODS: A single center, prospective, observational study. We analyzed bedside sublingual microcirculation in twenty-four consecutive COVID-19-associated acute respiratory distress syndrome (ARDS) patients mechanically ventilated in an Intensive Care Unit (ICU), together with macro-hemodynamics, clinical parameters, echocardiography, and laboratory data at a single time-point after ICU admission. All participants were recruited between March and May 2020. RESULTS: The microcirculatory pattern was characterized by increased values of total vessel density and perfused vessel density, a reduced value of proportion of perfused vessels and microvascular flow index, and high values of heterogeneity index. The duration of mechanical ventilation before microcirculation assessment was inversely associated with the proportion of perfused vessels (p = 0.023). Within the macro-hemodynamic parameters, the right ventricle end-diastolic diameter was inversely associated with proportion of perfused vessels and microvascular flow index (p = 0.039 and 0.014, respectively) and directly associated with the heterogeneity index (p = 0.033). CONCLUSIONS: In COVID-19-associated ARDS patients, the microcirculation showed impaired quality of flow parameters coupled with a high vessel density.

Evaluation of the impact of surgical aortic valve replacement on short-term cardiovascular and cerebrovascular controls through spontaneous variability analysis.

We assessed the effect of surgical aortic valve replacement (SAVR) on cardiovascular and cerebrovascular controls via spontaneous variability analyses of heart period, approximated as the temporal distance between two consecutive R-wave peaks on the electrocardiogram (RR), systolic, diastolic and mean arterial pressure (SAP, DAP and MAP) and mean cerebral blood flow (MCBF). Powers in specific frequency bands, complexity, presence of nonlinear dynamics and markers of cardiac baroreflex and cerebral autoregulation were calculated. Variability series were acquired before (PRE) and after (POST) SAVR in 11 patients (age: 76±5 yrs, 7 males) at supine resting and during active standing. Parametric spectral analysis was performed based on the autoregressive model. Complexity was assessed via a local nonlinear prediction approach exploiting the k-nearest-neighbor strategy. The presence of nonlinear dynamics was checked by comparing the complexity marker computed over the original series with the distribution of the same index assessed over a set of surrogates preserving distribution and power spectral density of the original series. Cardiac baroreflex and cerebral autoregulation were estimated by assessing the transfer function from SAP to RR and from MAP to MCBF and squared coherence function via the bivariate autoregressive approach. We found that: i) orthostatic challenge had no effect on cardiovascular and cerebrovascular control markers in PRE; ii) RR variance was significantly reduced in POST; iii) complexity of SAP, DAP and MAP variabilities increased in POST with a greater likelihood of observing nonlinear dynamics over SAP compared to PRE at supine resting; iv) the amplitude of MCBF variations and MCBF complexity in POST remained similar to PRE; v) cardiac baroreflex sensitivity decreased in POST, while cerebrovascular autoregulation was preserved. SAVR induces important changes of cardiac and vascular autonomic controls and baroreflex regulation in patients exhibiting poor reactivity of cardiovascular regulatory mechanisms, while cerebrovascular autoregulation seems to be less affected.

Complexity and Nonlinearities of Short-Term Cardiovascular and Cerebrovascular Controls after Surgical Aortic Valve Replacement.

We assessed the effect of surgical aortic valve replacement (SAVR) on cardiovascular and cerebrovascular controls with particular attention to their complexity and presence of nonlinear behaviors via the analysis of spontaneous variability of heart period (HP), systolic and diastolic arterial pressure (SAP and DAP) and mean cerebral blood flow (MCBF). Variability series were acquired before (PRE) and after (POST) SAVR in 12 patients (age: 76±4.7 yrs, 7 males) at rest in supine position and during active standing. Complexity was assessed via a local nonlinear prediction approach exploiting the k-nearest neighbor strategy. The presence of nonlinear dynamics was checked by comparing the complexity marker computed over the original series with the distribution of values assessed over 100 surrogates preserving distribution and power spectral density of the original series but with random phases. We found that: i) HP variance was significantly reduced in POST; ii) the complexity of SAP and DAP variabilities increased in POST with a greater likelihood of observing nonlinear dynamics over SAP compared to PRE at supine rest; iii) the amplitude of MCBF fluctuations and its complexity in POST remained similar to PRE. SAVR induces important changes of the cardiac and vascular autonomic controls, while cerebrovascular regulation seems to be less affected.

Comparison of Causal and Non-causal Strategies for the Assessment of Baroreflex Sensitivity in Predicting Acute Kidney Dysfunction After Coronary Artery Bypass Grafting.

Coronary artery bypass graft (CABG) surgery may lead to postoperative complications such as the acute kidney dysfunction (AKD), identified as any post-intervention increase of serum creatinine level. Cardiovascular control reflexes like the baroreflex can play a role in the AKD development. The aim of this study is to test whether baroreflex sensitivity (BRS) estimates derived from non-causal and causal approaches applied to spontaneous systolic arterial pressure (SAP) and heart period (HP) fluctuations can help in identifying subjects at risk of developing AKD after CABG and which BRS estimates provide the best performance. Electrocardiogram and invasive arterial pressure were acquired from 129 subjects (67 ± 10 years, 112 males) before (PRE) and after (POST) general anesthesia induction with propofol and remifentanil. Subjects were divided into AKDs (n = 29) or no AKDs (noAKDs, n = 100) according to the AKD development after CABG. The non-causal approach assesses the transfer function from the HP-SAP cross-spectrum in the low frequency (LF, 0.04-0.15 Hz) band. BRS was estimated according to three strategies: (i) sampling of the transfer function gain at the maximum of the HP-SAP squared coherence in the LF band; (ii) averaging of the transfer function gain in the LF band; (iii) sampling of the transfer function gain at the weighted central frequency of the spectral components of the SAP series dropping in the LF band. The causal approach separated the two arms of cardiovascular control (i.e., from SAP to HP and vice versa) and accounted for the confounding influences of respiration via system identification and modeling techniques. The causal approach provided a direct estimate of the gain from SAP to HP by observing the HP response to a simulated SAP rise from the identified model structure. Results show that BRS was significantly lower in AKDs than noAKDs during POST regardless of the strategy adopted for its computation. Moreover, all the BRS estimates during POST remained associated with AKD even after correction for demographic and clinical factors. Non-causal and causal BRS estimates exhibited similar performances. Baroreflex impairment is associated with post-CABG AKD and both non-causal and causal methods can be exploited to improve risk stratification of AKD after CABG.

Causality analysis reveals the link between cerebrovascular control and acute kidney dysfunction after coronary artery bypass grafting.

BACKGROUND: Patients undergoing coronary artery bypass graft (CABG) surgery might experience postoperative complications and some of them, such as acute kidney dysfunction (AKD), are the likely consequence of hypoperfusion. We hypothesized that an impaired cerebrovascular control is a hallmark of a vascular damage that might favor AKD after CABG. OBJECTIVE: Our aim is to characterize cerebrovascular control in CABG patients through the assessment of the relationship between mean arterial pressure (MAP) and mean cerebral blood flow velocity (MCBFV) and to check whether markers describing MCBFV-MAP dynamical interactions could identify subjects at risk to develop postoperative AKD. APPROACH: MAP and MCBFV beat-to-beat series were extracted from invasive arterial pressure and transcranial Doppler recordings acquired simultaneously in 23 patients just before CABG after the induction of propofol general anesthesia. Subjects were divided into AKD group (n = 9, age: 68 ± 9, 8 males) and noAKD group (n = 14, age: 65 ± 8, 12 males) according to whether they developed postoperative AKD or not after CABG. We computed MAP and MCBFV time-domain and spectral markers as well as MCBFV-MAP cross-spectral indexes in very-low-frequency (VLF, 0.02-0.07 Hz), low-frequency (LF, 0.07-0.15 Hz) and high-frequency (HF, 0.15-0.30 Hz) bands. We also calculated model-based transfer entropy (TE) to quantify the degree of MCBFV dependence on MAP and vice versa. The null hypothesis of MCBFV-MAP uncoupling was tested via a surrogate approach associating MAP and MCBFV in different patients. MAIN RESULTS: Time, spectral and cross-spectral markers had a limited power in separating AKD from noAKD individuals. Conversely, TE from MAP to MCBFV was significantly above the level set by surrogates only in AKD groups and significantly larger than that computed in noAKD. SIGNIFICANCE: The reduced cerebrovascular autoregulation in AKD patients suggest a vascular impairment likely making them more at risk of hypoperfusion during CABG and AKD after CABG.

Short-term multiscale complexity analysis of cardiovascular variability improves low cardiac output syndrome risk stratification after coronary artery bypass grafting.

BACKGROUND: Low cardiac output syndrome (LCOS) is a myocardial dysfunction leading to systemic hypoperfusion, favored by particular conditions of the autonomic nervous system. LCOS is one of the adverse events that might occur after cardiac surgery. OBJECTIVE: The aim is to test the hypothesis that short-term multiscale complexity (MSC) analysis of heart period (HP) and systolic arterial pressure (SAP) variability series in the frequency bands typical of cardiovascular control could be fruitfully exploited in identifying subjects at risk of developing LCOS after coronary artery bypass graft (CABG). APPROACH: HP and SAP beat-to-beat series were derived from electrocardiogram (ECG) and invasive arterial pressure (AP) signal acquired in 128 patients scheduled for CABG before (PRE) and after (POST) the induction of general anesthesia with propofol and remifentanil. Subjects were labeled as LCOS (n = 14) and noLCOS (n = 114) according to the LCOS development. MSC markers were calculated as the complement to 1 of the modulus of the average position of the poles dropping in the low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.5 Hz) bands as derived from the autoregressive model of HP and SAP series. Traditional time and frequency domain indexes were also calculated. MAIN RESULTS: Traditional parameters were able to assess the depression of the cardiovascular regulation induced by general anesthesia, but showed weak performances in differentiating LCOS and noLCOS groups. Conversely, HP complexity in LF band and SAP complexity in HF band assessed during POST remained associated with LCOS even after entering a multivariate logistic regression model adjusted for clinical and demographic factors. SIGNIFICANCE: The MSC approach can be fruitfully applied to improve risk stratification for LCOS after CABG likely because MSC markers describe the dysfunction of the sympathetic control and the impairment of the mechanical properties of the heart in the LCOS group.

The combined effects of the microcirculatory status and cardiopulmonary bypass on platelet count and function during cardiac surgery.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass is associated with important changes in the microcirculation, usually attributed to endothelial dysfunction. Another common finding of cardiac surgery is postoperative thrombocytopenia and platelet loss of function. OBJECTIVE: To investigate the association between microvascular flow pattern and postoperative changes in platelet count and function in cardiac surgery patients. METHODS: Twelve adult cardiac surgery patients received microvascular circulation (sidestream darkfield sublingual mucosa analysis) and platelet count and function (multiple electrode aggregometry ADPtest and TRAPtest) assessment before and after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass, sublingual microcirculation showed a significantly (P = 0.001) decreased microvascular flow index and increased heterogeneity index (P = 0.006). Platelet function significantly decrease after cardiopulmonary bypass both at ADPtest (P = 0.011) and TRAPtest (P = 0.002). Preoperative patterns of poor microvascular perfusion (low perfused vessels density and total vessels density) were significantly associated with lower values of post-cardiopulmonary bypass platelet function (ADPtest, P = 0.009, TRAPtest, P = 0.031) and count (P = 0.048). CONCLUSIONS: A preoperative disturbance of the microcirculation is associated with a greater postoperative platelet dysfunction. Endothelial damage, chemical and mechanical stimuli are the possible link between the two patterns.