It is very important to assess the effectiveness of prone positioning (PP) in patients with severe acute respiratory distress syndrome (ARDS). However, it is difficult to identify patients who may benefit from PP. The purpose of this study was to investigate whether prone positioning potential (PPP) can be predicted by lung ultrasound in patients with ARDS. In this prospective study, 45 patients with ARDS were included for the assessment of PPP. A PP lung ultrasound examination (PLUE) protocol was performed in the dorsal regions of the lung in 16 areas at H0, H3, and H6 (0, 3, and 6 h after PP). The ultrasonography videos were blindly evaluated by two expert clinicians to classify the lung regions as normal pattern (N), moderate loss of lung aeration (B1), severe loss of lung aeration (B2), and consolidation (C). The aeration scores were collected at H0, H3, and H6. According to the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (P/F ratio) at 7 days, patients were classified into PPP-positive (P/F ratio >300) and PPP-negative groups; also, the patients were classified into survival and nonsurvival groups according to 28-day mortality. Aeration scores was compared at H0, H3, and H6. The scores were significantly reduced between H3 and H0, but there was no difference between H3 and H6. The aeration score variation (ASV) of the PPP-positive group between H3 and H0 was significantly higher than that in the PPP-negative group, and the sensitivity and specificity of ASV ≥5.5 for the PPP-positive group were 73.9% and 86.4%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.852 for the ASV. The ASV between H3 and H0 in the survival group was significantly higher than in the nonsurvival group. The sensitivity and specificity of ASV ≥7 for survival were 51.5% and 75%, respectively. The AUROC was 0.702 for the ASV. The PLUE protocol can be used to predict PPP and assess prognosis in patients with ARDS.
To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca2+ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2.
7 January 2019 in Intensive Care Medicine Experimental
Microcirculation dysfunction with blood flow heterogeneity is an important characteristic in sepsis shock. We hypothesized that impaired ability of red blood cells to release nitric oxide resulted in microcirculation dysfunction in sepsis shock. 4,4′-Diisothiocyanatostilbene-2,2′-disulfonic acid disodium salt hydrate (DIDS), an inhibitor of band3 protein, was used to inhibit S-nitrosohemoglobin-mediated nitric oxide release. Rabbits were randomly divided into four groups: control (n = 6), lipopolysaccharide (LPS) (n = 6), LPS + DIDS (n = 6), and control + DIDS group (n = 6). Macrocirculation (cardiac output and mean arterial pressure) and microcirculation (microvascular flow index and flow heterogeneity index) parameters were recorded. At 2-h time point, arterial and venous S-nitrosohemoglobin concentrations were measured. The arterial–venous difference for S-nitrosohemoglobin in the LPS group was lower than the control group (27.3 ± 5.0 nmmol/L vs. 40.9 ± 6.2 nmmol/L, P < 0.05) but was higher than the LPS + DIDS group, with a statistically significant difference (27.3 ± 5.0 nmmol/L vs. 16.0 ± 4.2 nmmol/L, P < 0.05). Microvascular flow index for the LPS group at 2 h was lower than the control group (1.13 ± 0.16 vs. 2.82 ± 0.08, P < 0.001) and higher than the LPS + DIDS group (1.13 ± 0.16 vs. 0.84 ± 0.14, P < 0.05). Flow heterogeneity index for the LPS group at 2 h was higher than the control group (1.03 ± 0.27 vs. 0.16 ± 0.06, P < 0.001) and lower than the LPS + DIDS group (1.03 ± 0.27 vs. 1.78 ± 0.46, P < 0.001). In endotoxic shock rabbits, the ability of S-nitrosohemoglobin-mediated nitric oxide release from RBC was impaired, and there was an association between the ability and microcirculation dysfunction especially increased blood flow heterogeneity.
Respiratory variation of inferior vena cava is problematic in predicting fluid responsiveness in patients with right ventricular dysfunction. However, its effectiveness in patients with isolated left ventricular systolic dysfunction (ILVD) has not been reported. We aimed to explore whether inferior vena cava diameter distensibility index (dIVC) can predict fluid responsiveness in mechanically ventilated ILVD patients. Patients admitted to the intensive care unit who were on controlled mechanical ventilation and in need of a fluid responsiveness assessment were screened for enrolment. Several echocardiographic parameters, including dIVC, tricuspid annular plane systolic excursion (TAPSE), left ventricular ejection fraction (LVEF), and LV outflow tract velocity–time integral (VTI) before and after passive leg raising (PLR) were collected. Patients with LV systolic dysfunction only (TAPSE ≥ 16 mm, LVEF < 50%) were considered to have isolated left ventricular systolic dysfunction (ILVD). One hundred and twenty-nine subjects were enrolled in this study, among them, 28 were labelled ILVD patients, and the remaining 101 were patients with normal LV function (NLVF). The value of dIVC in ILVD patients was as high as that in NLVF patients, (20% vs. 16%, p = 0.211). The ILVD group contained a much lower proportion of PLR responders than NLVF patients did (17.9% vs. 53.2%, p < 0.001). No correlation was detected between dIVC and ΔVTI in ILVD patients (r = 0.196, p = 0.309). dIVC was correlated with ΔVTI in NLVF patients (r = 0.722, p < 0.001), and the correlation was strengthened compared with that derived from all patients (p = 0.020). A receiver-operating characteristic (ROC) analysis showed that the area-under-the-curve (AUC) of dIVC for determining fluid responsiveness from ILVD patients was not statistically significant (p = 0.251). In NLVF patients, ROC analysis revealed an AUC of 0.918 (95% CI 0.858–0.978; p < 0.001), which was higher than the AUC derived from all patients (p = 0.033). Patients with LVEF below 40% had a lower ΔVTI and fewer PLR responders than those with LVEF 40–50% and LVEF above 50% (p < 0.001). dIVC should be used with caution when critically ill patients on controlled mechanical ventilation display normal right ventricular function in combination with abnormal left ventricular systolic function.
Although the role of serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of sepsis and septic shock is well studied, it has not been investigated among oldest old patients. The aim of our study is to determine the role of PCT and hs-CRP in the assessment of sepsis and septic shock in this specific group of patients in the ICU. This is a prospective observational study. Patients >85 years of age admitted to the ICU from May 1st, 2016 to February 1st, 2017 were evaluated. Patients were divided into a sepsis and septic shock group(sepsis/SS) and a non-sepsis group. Serum levels of PCT, hs-CRP and the WBC were measured within 12 h of admission. A total of 70 patients aged 85 years and older were enrolled in this study. Fifty patients were labelled as sepsis/SS and the other 20 were labelled non-sepsis. A ROC analysis showed that the area under the curves (AUC) of hs-CRP and PCT for the discrimination of sepsis/SS patients were 0.825 (95% confidence interval[CI]: 0.73-0.92; P < 0.001) and 0.819 (95%CI:0.72-0.92; p < 0.001), respectively. In a subgroup analysis of the sepsis/SS group, 27 patients had sepsis, while the other 23 patients had septic shock. The ROC analysis showed that the AUCs of hs-CRP and PCT for the discrimination of septic shock patients from sepsis patients were 0.751 (95% CI: 0.62-0.88; P = 0.002) and 0.719 (95% CI:0.57-0.86; p = 0.007), respectively. For the oldest old patients, hs-CRP is not inferior to PCT in the diagnosis of sepsis and septic shock.
30 November 2022 in Computers in Biology and Medicine