Decreased Heart Rate Variability in COVID-19.

Purpose: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which primarily infects the lower airways and binds to angiotensin-converting enzyme 2 (ACE2) on alveolar epithelial cells. ACE2 is widely expressed not only in the lungs but also in the cardiovascular system. Therefore, SARS-CoV-2 can also damage the myocardium. This report aimed to highlight decreased heart rate variability (HRV) and cardiac injury caused by SARS-CoV-2. Materials and Methods: We evaluated three COVID-19 patients who died. Patients' data were collected from electronic medical records. We collected patient's information, including baseline information, lab results, body temperature, heart rate (HR), clinical outcome and other related data. We calculated the HRV and the difference between the expected and actual heart rate changes as the body temperature increased. Results: As of March 14, 2020, 3 (2.2%) of 136 patients with COVID-19 in Tianjin died in the early stage of the COVID-19 epidemic. The immediate cause of death for Case 1, Case 2, and Case 3 was cardiogenic shock, cardiac arrest and cardiac arrest, respectively. The HRV were substantially decreased in the whole course of all three cases. The actual increases in heart rate were 5 beats/min, 13 beats/min, and 4 beats/min, respectively, less than expected as their temperature increased. Troponin I and Creatine Kinase MB isoenzyme (CK-MB) were substantially increased only in Case 3, for whom the diagnosis of virus-related cardiac injury could not be made until day 7. In all three cases, decreased in HRV and HR changes occurred earlier than increases in cardiac biomarkers (e.g., troponin I and CK-MB). Conclusions: In conclusion, COVID-19 could affect HRV and counteract tachycardia in response to increases in body temperature. The decreases of HRV and HR changes happened earlier than the increases of myocardial markers (troponin I and CK-MB). It suggested the decreases of HRV and HR changes might help predict cardiac injury earlier than myocardial markers in COVID-19, thus its early identification might help improve patient prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s44231-022-00024-1.

[A clinical study on the wean effect of setting parameters of proportional pressure support on acute exacerbation of chronic obstructive pulmonary disease patients with difficult weaning].

OBJECTIVE: To investigate the clinical effect of setting proportional pressure support (PPS) parameters by target tidal volume (VT) method. METHODS: The study was conducted retrospectively on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients admitted to Tianjin Third Central Hospital from January 2016 to December 2020. According to the PPS parameter setting method, the patients were divided into the airway blocking group and target VT group. The baseline characteristics, initial setting values of flow assist (FA) and volume assist (VA), respiratory system parameters, and clinical outcomes were collected and compared between the two groups. RESULTS: Fifty-nine patients were enrolled, 29 patients in the airway blocking group, and 30 in the target VT group. There was no statistically significant difference in baseline characteristics, compliance, resistance, and initial settings of FA and VA between the two groups. Compared with the target VT group, the respiratory rate (RR), mean arterial pressure (MAP), VT, and arterial partial pressure of oxygen (PaO2) recorded 1 hour after the initial setting of the PPS parameters in the airway block method group were significantly reduced [RR (times/minute): 21.0 (18.5, 22.5) vs. 23.0 (21.0, 25.0), MAP (mmHg, 1 mmHg = 0.133 kPa): 84.0 (79.0, 90.5) vs. 90.0 (87.0, 96.2), VT (mL): 305.24±41.07 vs. 330.87±46.84, PaO2 (mmHg): 68.0 (66.0, 73.5) vs. 74.0 (69.8, 82.5), all P < 0.05], while arterial partial pressure of carbon dioxide (PaCO2) and oral closure pressure (P0.1) were both increased significantly [PaCO2 (mmHg): 41.0 (39.0, 46.0) vs. 37.5 (35.0, 42.2), P0.1 (cmH2O, 1 cmH2O = 0.098 kPa): 1.42±0.78 vs. 0.90±0.67, both P < 0.05]. Compared with airway blocking group, the duration of weaning, ICU stay, and hospital stay in the target VT group were significantly shorter [duration of weaning (hours): 42.0 (24.0, 70.5) vs. 64.0 (30.5, 97.5), ICU stay: 10.00±3.38 to 13.28±5.41, hospital stay (days): 12.07±3.40 vs. 15.41±5.60, all P < 0.05]. There was no statistically significant difference in the invasive mechanical ventilation time, weaning failure rate, ICU mortality and in-hospital mortality between the two groups. CONCLUSIONS: This study suggested that the target TV method has the advantages of practicality, safety, convenience, and rapid to set PPS parameters than the airway block method, which shortens the duration of weaning and ICU stay, and has a good clinical prospect.

[Preliminary establishment of weaning prediction model].

OBJECTIVE: To establish a model that can predict weaning failure from ventilation through hemodynamic and fluid balance parameters. METHODS: A retrospective analysis was conducted. The patients who underwent invasive mechanical ventilation for more than 24 hours and having spontaneous breathing test admitted to intensive care unit (ICU) of Tianjin Third Central Hospital from January 1st, 2017 to December 31st, 2018 were enrolled. The information was collected, which included the baseline data, hemodynamic parameters by pulse indicator continuous cardiac output (PiCCO) monitoring, B-type natriuretic peptide (BNP), urinary output, fluid balance in first 24 hours when patients admitted to ICU, and hemodynamic parameters by PiCCO monitoring, BNP, urinary output, fluid balance, diuretic usage, noradrenalin usage within 24 hours before weaning as well as usage of continuous renal replacement therapy (CRRT) during mechanical ventilation. According to weaning success or failure, the patients were divided into weaning success group and weaning failure group, and the statistical differences between the two groups were calculated. Variables with statistical significance within 24 hours before weaning were included in the multivariate Logistic regression analysis to establish weaning failure prediction model and find out the possible risk factors of weaning failure. RESULTS: A total of 159 patients were included in this study, which included 138 patients in the weaning success group and 21 patients in the weaning failure group. There were no statistical differences in all hemodynamic parameters by PiCCO monitoring, BNP, urinary output, fluid balance within 24 hours into ICU between two groups. There were statistical differences in BNP (χ2 = 9.262, P = 0.026), central venous pressure (CVP; χ2 = 7.948, P = 0.047), maximum rate of the increase in pressure (dPmx; χ2 = 10.486, P = 0.015), urinary output (χ2 = 8.921, P = 0.030), fluid balance (χ2 = 9.172, P = 0.027) within 24 hours before weaning between two groups. In addition, variable about cardiac index (CI; χ2 = 7.789, P = 0.051) was included into multivariate Logistic regression model to improve the prediction model and enhance the accuracy of model. Finally, variables included in the multivariate Logistic regression model were BNP, CVP, CI, dPmx, urinary output, fluid balance volume, and the accuracy of the weaning failure prediction model was 92.9%, the sensitivity was 100%, and the specificity was 76.8%. When the model was adjusted by variables of age and noradrenalin usage, the accuracy of model to predict failure of weaning was 94.2%, the sensitivity was 100%, the specificity was 81.2%. CONCLUSIONS: Weaning failure prediction model based on hemodynamic parameters by PiCCO monitoring and variables about liquid balance has high accuracy and can guide clinical weaning.

Transplantation of in vitro cultured endothelial progenitor cells repairs the blood-brain barrier and improves cognitive function of APP/PS1 transgenic AD mice.

To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well-known that excessive deposition of Aß in the brain is a crucial part of the pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has attracted much attention. Impairment of the blood-brain barrier (BBB) leads to abnormal amyloid-ß (Aß) transport, and chronic cerebral hypoperfusion causes Aß deposition throughout the onset and progression of AD. Endothelial progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our previous studies have shown that a reduced number of EPCs in the peripheral blood results in cerebral vascular repair disorder, cerebral hypoperfusion and neurodegeneration, which might be related to the cognitive dysfunction of AD patients. This study was designed to confirm whether EPCs transplantation could repair the blood-brain barrier, stimulate angiogenesis and reduce Aß deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent with previous studies, EPC transplants also increased the microvessel density. We observed that Aß senile plaque deposition was decreased and hippocampal cell apoptosis was reduced after EPCs transplantation. The Morris water maze test showed that spatial learning and memory functions were significantly improved in mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression of tight junction proteins, repair BBB tight junction function, stimulate angiogenesis, promote Aß clearance, and decrease neuronal loss, ultimately improve cognitive function. Taken together, these data demonstrate EPCs may play an important role in the therapeutic implications for vascular dysfunction in AD.

[Assessment of fluid volume in critically ill patients with extravascular lung water index].

OBJECTIVE: To examine the effect of rapid infusion test guided by extravascular lung water index ( EVLWI ) on hemodynamics in critically ill patients at different states in order to guide volume resuscitation. METHODS: A prospective observation was conducted. Forty critically ill patients admitted to Department of Critical Care Medicine of Tianjin Third Central Hospital from June 2012 to April 2014 were enrolled. Based on the levels of EVLWI and pulmonary vascular permeability index ( PVPI ) and the cardiac function, the patients were divided into four groups: septic patients with normal EVLWI and PVPI ( n = 17 ), septic patients with increased EVLWI and PVPI ( n = 3 ), septic patients with increased EVLWI and normal PVPI ( n = 4 ), and coronary heart disease and heart failure patients with normal EVLWI and PVPI ( n = 16 ). The rapid infusion test was conducted in all patients using lactated Ringer solution 250 mL, followed by infusion of crystalloid with rate of 150 mL/h. The conditions of mechanical ventilation and vasoactive drugs were not changed during study. The changes in EVLWI, intrathoracic blood volume index ( ITBVI ), and cardiac index ( CI ) before capacity load, at immediate capacity load, and 15, 45, 105 minutes after load were determined by pulse indicator continuous cardiac output ( PiCCO ). On the base of volume status before and after the liquid infusion, the standard for the changes were: stroke volume ( SV ) increased by 12%-15%, central venous pressure ( CVP ) greater ≥ 2 mmHg ( 1 mmHg = 0.133 kPa ), CI>15%, and ITBVI change greater than 10%. RESULTS: There were no statistically significant differences in the observed indicators at the each time point before and after rapid infusion test among the four groups ( all P>0.05 ). In septic patients with normal EVLWI and PVPI group, ITBVI was slightly increased by 5.4%-9.7% from 15 minutes to 45 minutes after rapid infusion test. In coronary heart disease and heart failure patients with normal EVLWI and PVPI group, the EVLWI was increased by 11.9%, 5.9%, and 14.7% respectirely at 15, 45, and 105 minutes, ITBVI was slightly increased by 6.4% at 45 minutes, CI was increased by 29.5% immediately after rapid infusion. In septic patients with increased EVLWI and PVPI group, CVP was increased by 8 mmHg immediately, EVLWI was increased significantly by 15.8% at 45 minutes, ITBVI was slightly decreased by 10.0% at 45 minutes, CI was increased by 24.7% immediately, and increased by 17.0% at 105 minutes, and PVPI was increased by 15.6%-28.1% at 15-105 minutes after rapid infusion. In septic patients with increased EVLWI and normal PVPI group, CVP was increased by 1.5 mmHg at 15 minutes, EVLWI was increased immediately, which was increased by 17.4%, 24.0%, and 31.4% respectively at 15, 45, and 105 minutes, ITBVI was increased by 13.9% at 15 minutes, CI was increased by 16.1% at 15 minutes after rapid fluid infusion. CONCLUSIONS: Rapid fluid replacement in critically ill patients with crystalloid, regardless of whether the EVLWI was normal or increased, the short-term response was affected by the volume and cardiac function of patients. Different status of patients showed different volume effect curve: no significant changes in hemodynamic parameters were found in patients with normal EVLWI and volume parameters. In patients with potential cardiac dysfunction, CI and EVLWI increased significantly; regardless of PVPI increased or normal, EVLWI and CI were increased in patients with elevated EVLWI; two different changes could be found in the two types of pulmonary edema while ITBVI was increased.

[The influence of continuous venovenous hemofiltration on parameter measurement by the transpulmonary thermodilution technique].

OBJECTIVE: To evaluate the influence of continuous venovenous hemofiltration (CVVH) on measurement of transpulmonary thermodilution parameters. METHODS: A prospective observational study was conducted. Fifty-six patients who received CVVH and hemodynamic monitoring at the same time admitted to the Department of Critical Care Medicine of Tianjin Third Central Hospital from July 2012 to July 2014 were enrolled. In all the patients, the dialysis catheter was inserted through the femoral vein, and transpulmonary thermodilution measurements were performed by pulse indicator continuous cardiac output (PiCCO) monitoring technology at the same time. Mean arterial pressure (MAP), central blood temperature, cardiac index (CI), global end-diastolic volume index (GEDVI), intrathoracic blood volume index (ITBVI) and extravascular lung water index (EVLWI) were measured before CVVH, immediately after CVVH, and 30 minutes after CVVH, respectively. Results In the 56 patients, there were 36 males and 20 females, (66 ± 16) years of old, height of (172 ± 6) cm, body weight of (68 ± 10) kg. The acute physiology and chronic health evaluation II (APACHE II) scores was 26 ± 6. After CVVH, the central blood temperature was gradually decreased, and blood temperature at 30 minutes after CVVH was significantly lower than that before CVVH (degrees C : 37.17 ± 1.06 vs. 37.57 ± 1.26, P < 0.01). There were no significant changes in MAP and EVLWI before and after CVVH the MAP was (89 ±20), (86 ± 16), (90 ± 17) mmHg ( 1 mmHg = 0.133 kPa) at three time points respectively, and EVLWI was (9.4 ± 3.2, (9.3 ± 3.0), (9.4 ± 2.9) mL/kg, respectively. After CVVH, CI, GEDVI and ITBVI showed a gradual downward tendency. Compared with those before CVVH, the decline of CI, GEDVI, and ITBVI immediately after CVVH was not statistically significant [CI (mL x s (-1) x m(-2): 62.18 ± 24.34 vs 63.85 ± 21.84, GEDVI (mL/m2): 705 ± 103 vs 727 ± 100, ITBVI (mL/m2): 881 ± 129 vs 908 ± 125, all P > 0.05]. CI, GEDVI, ITBVI at 30 minutes after CVVH were significantly decreased [CI mL x s(-1) x m(-2)): 57.84 ± 20.50 vs 63.85 ± 21.84, GEDVI (mL/m2): 681 ± 106 vs. 727 ± 100, ITBVI (mL/m2): 851 ± 133 vs. 908 ± 125, all P < 0.05]. CVVH was associated with a decline of 6.01 mL x s(-1) x m(-2) at 30 minutes after CVVH [95% confidence interval (95% CI)) = -10.67 to -1.50, P = 0.011]. The declines of GEEDVI and ITBVI were observed with 46 mL/m2 (95% CI = -81 to - 11, P = 0.014), 57 mL/m2 (95% CI = -101 to -13, P = 0.014) respectively 30 minutes after CVVH. CONCLUSIONS: CVVH had no significant effect on the transpulmonary thermodilution measurement of CI, GEDVI, ITBVI and EVLWI. Thirty minutes after the start of CVVH, CI, GEDVI was decreased significantly, but had no effect on EVLWI.