Serratus anterior plane block for video-assisted thoracoscopic surgery: A meta-analysis of randomised controlled trials.

BACKGROUND: The serratus anterior plane block (SAPb) is a promising interfascial plane technique able to provide profound thoracic analgesia. As only a few studies with quite small patient samples are presently available, the analgesic efficacy of adding SAPb to general anaesthesia in video-assisted thoracoscopic surgery (VATS), compared with general anaesthesia only, remains unclear. OBJECTIVES: Our primary aim was to assess the analgesic efficacy of SAPb for VATS peri-operative pain control. The secondary aims were to evaluate differences in postoperative opioid use, intra-operative hypotension, postoperative side-effects and complications, time to chest tube removal, length of hospital stay. DESIGN: Systematic review of randomised controlled trials (RCTs) with meta-analyses.DATA SOURCES PubMed, Web of Science, Google Scholar and the Cochrane Library, searched up to 6 December 2019.ELIGIBILITY CRITERIA RCTs including adult patients undergoing VATS who received single shot SAPb (cases), compared with general anaesthesia (controls). RESULTS: Seven RCTs, with a total of 489 patients were included. SAPb reduced pain scores peri-operatively, compared with controls: 6 h [mean difference -1.86, 95% confidence interval (CI) -2.35 to -1.37, P < 0.001]; 12 h (mean difference -1.45, 95% CI -1.66 to -1.25, P < 0.001); 24 h (mean difference -0.98, 95% CI -1.40 to -0.56, P < 0.001). SAPb also reduced the use of postoperative opioids (mean difference: -4.81 mg of intravenous morphine equivalent, 95% CI -8.41 to -1.22, P < 0.03) and decreased the incidence of nausea and vomiting (risk ratio 0.53, 95% CI 0.36 to 0.79, P < 0.002). CONCLUSION: Compared with general anaesthesia only and if no other locoregional techniques are used, SAPb significantly reduces postoperative pain and nausea and vomiting in patients undergoing VATS. Grading of Recommendations Assessment, Development and Evaluation rating are, nonetheless, quite low, due to high heterogeneity. Well designed and properly powered RCTs are necessary to confirm these preliminary findings.

Whole-blood hypocoagulable profile correlates with a greater risk of death within 28 days in patients with severe sepsis.

BACKGROUND: Hypocoagulability and impaired platelet function have been associated with a high risk of death in sepsis. The aim of this cohort study was to determine whether sepsis-induced hypocoagulability and platelet dysfunction (assessed by ROTEM® and MULTIPLATE®, respectively) are increased in sepsis patients who died within 28 days after diagnosis compared with patients who died between 29 and 90 days after diagnosis. METHODS: Consecutive patients admitted to the intensive care unit of Padova University Hospital from March 2015 to March 2018 for severe sepsis were considered. We collected blood samples from all patients to determine ROTEM® and MULTIPLATE® parameters. Each enrolled patient underwent a 90-day follow-up and the mortality rate was recorded. RESULTS: Of 120 patients, 36 (30%) died within 28 days post-diagnosis (Group A), 23 (19%) died between days 29 and 90 post-diagnosis (Group B), and 61 (51%) were alive after 90 days (survivors). The clotting time in the ROTEM® test and clot formation time in the EXTEM test were significantly more prolonged in Group A than in B. Both groups showed a significantly higher hypocoagulability than survivors in the EXTEM test. MULTIPLATE® platelet function analysis showed that platelet function was significantly lower in Group A than in Group B. CONCLUSIONS: The present study showed that the combination of thromboelastometry and impedance aggregometry may help identifying sepsis patients at high risk of short-term death. Larger studies are warranted to corroborate our results.

Levels of circulating microparticles in septic shock and sepsis-related complications: a case-control study.

BACKGROUND: Microparticles (MP) have been largely studied as potential biomarkers in septic shock (SS) though their biological and clinical relevance is still unclear. This case-control study describes the trend of various MP subtypes during SS to evaluate their possible association with severity of illness and sepsis-related complications (disseminated intravascular coagulation [DIC] and acute kidney injury [AKI]). METHODS: Forty patients admitted to the Intensive Care Unit with SS and 40 matched healthy volunteers were recruited. AnnexinV+, E-selectin+, thrombomodulin (TM+), leukocyte-derived (CD45+, CD36+) and platelet-derived MP (PMP-expressed as PMP/platelets ratio) were measured by flow-cytometry at baseline, on day 1, 3 and 7 after diagnosis. Severity of illness was assessed by Sequential Organ Failure Assessment Score, duration of vasoactive support and mechanical ventilation. Sepsis-related complications were considered. RESULTS: Overall, septic patients showed higher levels of all MP considered compared to controls. TM+MP were significantly lower in more severe sepsis, while CD36+MP and PMP/platelets ratio were significantly increased in patients requiring longer vasoactive support and mechanical ventilation. As for sepsis-related complications, a higher PMP/platelets ratio in patients who developed DIC and increased E-selectin+MP in subjects who developed AKI were observed. PMP/platelets ratio at baseline was significantly associated with longer vasoactive support (OR=1.59 [1.05-2.42]), longer mechanical ventilation (OR=1.6 [1.06-2.42]) and DIC occurrence (OR=1.45 [1.08-1.96]). CONCLUSIONS: A global response through extra-vesiculation of endothelial cells, leukocytes and platelets during the early stages of SS was confirmed. The cellular activation was detected until day 3 after diagnosis. PMP/platelets ratio at diagnosis may be useful to evaluate SS severity and DIC occurrence.

Relationship between mitral annulus function and mitral regurgitation severity and left atrial remodelling in patients with primary mitral regurgitation.

AIMS: To explore the relationship between the mitral annular (MA) remodelling and dysfunction, mitral regurgitation (MR) severity, left ventricular (LV) and atrial (LA) size and function in patients with organic MR (OMR). METHODS AND RESULTS: A total of 52 patients (57 ± 15 years, 31 men) with mild to severe OMR and 52 controls underwent 3D transthoracic echocardiography acquisitions of the mitral valve (MV), LA, and LV. MA geometry and dynamics, LV and LA volumes, LV ejection fraction (LVEF) and emptying fractions (LAEF) were assessed using dedicated software packages. LA and LV myocardial deformations were assessed using 2D speckle-tracking echocardiography. OMR patients presented larger and more spherical MA than controls during the entire systole (P < 0.001). Although the MA non-planarity at early-systole was similar between OMR and controls (157 ± 13° vs. 153 ± 12°, P = NS), the MA became flatter from mid- to end-systole (153 ± 12 vs. 146 ± 10° and 157 ± 12 vs. 147 ± 8°, P < 0.01) in OMR. MA area fractional change was lower in patients with OMR (22 ± 5% vs. 28 ± 5%, P < 0.001), and correlated with the MR orifice and volume (r = -0.52 and r = -0.55). MA fractional area change correlated with LA minimum and maximum volumes (r = 0.77 and r = 0.70), total and active LAEF (r = 0.72 and r = 0.76), and LA negative strain and strain rate (r = 0.52 and r = 0.57), but not with the LVEF or LV global longitudinal strain. In a multivariate regression model using LAEF and LVEF, solely active LAEF correlated with the MA fractional area change (ß = 0.51, P = 0.005). CONCLUSION: In patients with OMR, MA reduced function correlates with the MR severity and the LA size and function, but not with the LV function.

Normal mitral annulus dynamics and its relationships with left ventricular and left atrial function.

Mitral annulus (MA) geometry and dynamics are crucial for preserving normal mitral valve (MV) function. Static reference values for MA parameters have been reported, but the normal MA dynamics during the entire cardiac cycle remains controversial. MV full-volume datasets were obtained by three-dimensional transthoracic echocardiography from 50 healthy volunteers (18-74 years; 31 men) to assess MA changes in size and shape during entire cardiac cycle. Using simultaneous multiplanar review, projected MA area (MAA) and circumference (MAC), antero-posterior (AP) and anterolateral-posteromedial (ALPM) diameters, and sphericity index (SphI) were obtained at: mitral valve closure (MVC), mid- and end-systole (ES), early- (EDF) and late-diastolic filling, and end-diastole. MAA and AP diameter were the most "active" parameters, changing in all reference frames (p < 0.001). MAA and AP diameter started to contract before MVC (during the left atrial contraction), reaching their minimum at MVC. Maximum MAA occurred at ES, while maximum AP diameter and SphI occurred at EDF. MAA fractional shortening was 35 ± 10 %. AP diameter change was 25 ± 10 %. MAC, ALPM and SphI showed similar patterns during left ventricular (LV) systole, and remained unchanged during diastole. Fractional change was 35 ± 10 % for MAC, and 13 ± 8 % for ALPM diameter. Our study provides the normal dynamics of the MA during the entire cardiac cycle. It reveals "pre-systolic" contraction of the MA, related to left atrial (LA) contraction, and minimal MAA during early LV systole. Therefore, the normal MA dynamics relates to a "physiologic LA-LV coupling", and a complete MA contraction requires both and properly timed LA and LV systole.

Quantitative analysis of mitral annular geometry and function in healthy volunteers using transthoracic three-dimensional echocardiography.

BACKGROUND: Quantitative assessment of the mitral annulus provides information regarding the pathophysiology of mitral regurgitation and aids in the planning of reparative surgery. Three-dimensional (3D) transthoracic echocardiographic data sets acquired with current scanners have enough spatial and temporal resolution to allow the quantitative analysis of the mitral annulus. Accordingly, the authors performed (1) a validation study to assess the agreement of quantitative analysis of the mitral annulus performed on 3D transthoracic echocardiography (TTE) and 3D transesophageal echocardiography (TEE) and (2) a normative study to obtain the reference values of 3D transthoracic echocardiographic parameters for mitral annular (MA) geometry and dynamics. METHODS: Mitral valve data sets were obtained by 3D TEE and 3D TTE in 30 consecutive patients with clinically indicated TEE (validation study) and 3D TTE in 224 healthy volunteers (aged 18-76 years) (normative study). RESULTS: In the validation study, MA measurements obtained by 3D TTE were similar to those obtained by 3D TEE (P = NS). In the normative study, MA analysis by 3D TTE was feasible (94.5%) and reproducible (intraclass correlation coefficient = 0.78-0.97). MA diameters, area, and circumference were correlated with body surface area (r > 0.50 for all) but not with age. Men had larger MA areas than women (4.9 ± 1.0 vs 4.5 ± 0.7 cm(2)/m(2), P = .004). During systole, MA area decreased by 29 ± 5%. This decrease was related mainly to anteroposterior diameter shortening (20 ± 7%). CONCLUSIONS: MA quantitative analysis by 3D TTE was accurate compared with 3D TEE in unselected patients with mitral valve disease. In healthy subjects, it was highly feasible and reproducible. The availability of reference values for MA geometry and dynamics may foster the implementation of MA quantitative analysis by 3D TTE in clinical settings.

Ascending aorta diameters measured by echocardiography using both leading edge-to-leading edge and inner edge-to-inner edge conventions in healthy volunteers.

AIMS: Reference ranges of ascending aorta diameters (AAoD) for two-dimensional echocardiography (2DE) using inner edge (IE) convention are lacking, preventing the comparison of AAoD measurements by 2DE with those obtained by other imaging modalities. METHODS AND RESULTS: We used harmonic imaging 2DE to prospectively study 218 healthy volunteers (56% women, 42 ± 15 years, 18-80 years). Measurements were performed at the level of aortic root (AoR), sinotubular junction (STJ), and proximal tubular portion (TAo, 1 cm from the STJ) using both leading edge (LE) and IE conventions at end-diastole and end-systole. Feasibility of AAoD measurements between end-diastole and end-systole was similar at AoR and STJ levels, but it was significantly different at TAo level (82 vs. 96%, respectively, P < 0.0001). Ascending aorta diameters indexed to height were larger in men than in women (P < 0.0001). After adjusting for the effect of gender, only age and body surface area (BSA) were independent predictors of AAoD at multivariable analysis. Average end-diastolic AoR, STJ, and TAo diameters measured using IE convention were similar between genders (17 ± 2, 15 ± 2, and 15 ± 2 mm/m(2), respectively). Corresponding AAoD measured using the LE convention were 18 ± 2, 16 ± 2, and 17 ± 4 mm/m(2), respectively. On average, the end-systolic AAoD measured using LE were 2 mm larger than those performed using IE or at end-diastole. Mean aortic wall thickness was 2.4 ± 0.8 mm. CONCLUSION: End-diastolic AAoD measured using IE were significantly smaller than those obtained either using LE convention or at end-systole. Gender-specific reference values for AAoD indexed for BSA should be used to identify ascending aorta pathology.

Cardiac sympathetic neurons provide trophic signal to the heart via ß2-adrenoceptor-dependent regulation of proteolysis.

AIMS: Increased cardiac sympathetic neuron (SN) activity has been associated with pathologies such as heart failure and hypertrophy, suggesting that cardiac innervation regulates cardiomyocyte trophism. Whether continuous input from the SNs is required for the maintenance of the cardiomyocyte size has not been determined thus far. METHODS AND RESULTS: To address the role of cardiac innervation in cardiomyocyte size regulation, we monitored the effect of pharmacological sympathetic denervation in mice on cardiac structure, function, and signalling from 24 h to 30 days in the absence of other pathological stimuli. SN ablation caused an immediate reduction in the cardiomyocyte size with minimal consequences on the resting contractile function. Atrophic remodelling was mediated by the ubiquitin-proteasome system through FOXO-dependent early induction of the muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1, which was followed by activation of the autophagy-lysosome system. MuRF1 was found to be determinant in denervation atrophy as remodelling did not develop in denervated MuRF1 knock-out (KO) hearts. These effects were caused by decreased basal stimulation of cardiomyocyte ß2-adrenoceptor (AR), as atrophy was prevented by treatment of denervated mice with the ß2-AR agonist clenbuterol. Consistent with these data, we also observed that ß2-AR KO mice showed cardiac atrophy at rest. CONCLUSION: Cardiac SNs are strong regulators of the cardiomyocyte size via ß2-AR-dependent repression of proteolysis, demonstrating that the neuro-cardiac axis operates constitutively for the determination of the physiological cardiomyocyte size. These results are of great clinical relevance given the role of ß-AR in cardiovascular diseases and their modulation in therapy.