Venous Pressure

BackgroundThe association of central venous pressure (CVP) and mortality and acute kidney injury (AKI) in critically ill adult patients remains unclear. We performed a meta-analysis to determine whether elevated CVP is associated with increased mortality and AKI in critically ill adult patients.MethodsWe searched PubMed and Embase through June 2019 to identify studies that investigated the association between CVP and mortality and/or AKI in critically ill adult patients admitted into the intensive care unit. We calculated the summary odds ratio (OR) and 95% CI using a random-effects model.ResultsFifteen cohort studies with a broad spectrum of critically ill patients (mainly sepsis) were included. On a dichotomous scale, elevated CVP was associated with an increased risk of mortality (3 studies; 969 participants; OR, 1.65; 95% CI, 1.19-2.29) and AKI (2 studies; 689 participants; OR, 2.09; 95% CI, 1.39-3.14). On a continuous scale, higher CVP was associated with greater risk of mortality (5 studies; 7837 participants; OR, 1.10; 95% CI, 1.03-1.17) and AKI (6 studies; 5446 participants; OR, 1.14; 95% CI, 1.06-1.23). Furthermore, per 1 mmHg increase in CVP increased the odds of AKI by 6% (4 studies; 5150 participants; OR, 1.06; 95% CI, 1.01-1.12). Further analyses restricted to patients with sepsis showed consistent results.ConclusionsElevated CVP is associated with an increased risk of mortality and AKI in critically ill adult patients admitted into the intensive care unit.Trial registrationPROSPERO, CRD42019126381.

Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non-invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information.

ImportanceManeuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes.ObjectiveTo describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients.RegistrationThe protocol was registered at PROSPERO: CRD42019146781.Information sources and searchPubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023.Study selection and data collectionProspective and intervention studies were selected.Statistical analysisData for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed.ResultsA total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89).ConclusionsFluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

Rationale: Metabolic remodeling occurs during partial hepatectomy (PHx)-induced liver regeneration. Phospholipid remodeling during this process and its subsequent impact on liver regeneration remain unknown. The remnant liver's ability to defend against injury is also essential for normal liver regeneration, although the underlying mechanisms remain unclear. Methods: Phospholipidomics was performed to describe phospholipid remodeling after 70% PHx. Phosphate cytidylyltransferase 2, ethanolamine (PCYT2) was overexpressed in hepatocytes using adeno-associated virus under the thyroxine-binding globulin promoter. An ex vivo liver perfusion system was used to regulate portal pressure. GalNAc-conjugated PEG-PCL nano-particles (NPs) were developed to deliver the PCYT2 inhibitor, meclizine. Results: We found a significant decrease in a series of phosphatidylethanolamine (PE) levels at 1 day after 70% PHx. PCYT2, an enzyme for PE synthesis, was downregulated by PHx. Higher portal pressure-induced shear stress is an early event after PHx. As a target gene of hepatocyte nuclear factor 4α, PCYT2 levels were decreased by higher portal pressure. Hepatocyte-specific PCYT2 overexpression aggravated liver damage after PHx by increasing reactive oxygen species levels, lipid peroxidation, and mitochondrial fragmentation. We observed higher hepatic PCYT2 levels in middle-aged mice than in young mice. PCYT2 inhibition by meclizine facilitates liver regeneration in middle-aged mice. Meclizine is also a blocker of the histamine H1 receptor, a membrane receptor. Therefore, we used NPs to deliver meclizine into cells to better target PCYT2 and prevent potential side effects. NP-meclizine improved liver regeneration in middle-aged mice, demonstrating higher therapeutic efficacy than carrier-free meclizine. Conclusions: Decreased PCYT2 levels and PE content due to increased portal pressure protect hepatocytes from PHx-induced injury. Inhibiting PCYT2 with NP-meclizine promoted normal liver regeneration in middle-aged mice.