Butyrylcholinesterase activity in patients with postoperative delirium after cardiothoracic surgery or percutaneous valve replacement- an observational interdisciplinary cohort study.

BACKGROUND AND OBJECTIVES: Postoperative delirium is a frequent and severe complication after cardiac surgery. Activity of butyrylcholinesterase (BChE) has been discussed controversially regarding a possible role in its development. This study aimed to investigate the relevance of BChE activity as a biomarker for postoperative delirium after cardiac surgery or percutaneous valve replacement. METHODS: A total of 237 patients who received elective cardiothoracic surgery or percutaneous valve replacement at a tertiary care centre were admitted preoperatively. These patients were tested with the Montreal Cognitive Assessment investigating cognitive deficits, and assessed for postoperative delirium twice daily for three days via the 3D-CAM or the CAM-ICU, depending on their level of consciousness. BChE activity was measured at three defined time points before and after surgery. RESULTS: Postoperative delirium occurred in 39.7% of patients (n = 94). Univariate analysis showed an association of pre- and postoperative BChE activity with its occurrence (p = 0.037, p = 0.001). There was no association of postoperative delirium and the decline in BChE activity (pre- to postoperative, p = 0.327). Multivariable analysis including either preoperative or postoperative BChE activity as well as age, MoCA, type 2 diabetes mellitus, coronary heart disease, type of surgery and intraoperative administration of red-cell concentrates was performed. Neither preoperative nor postoperative BChE activity was independently associated with the occurrence of postoperative delirium (p = 0.086, p = 0.484). Preoperative BChE activity was lower in older patients (B = -12.38 (95% CI: -21.94 to -2.83), p = 0.011), and in those with a history of stroke (B = -516.173 (95% CI: -893.927 to -138.420), p = 0.008) or alcohol abuse (B = -451.47 (95% CI: -868.38 to -34.55), p = 0.034). Lower postoperative BChE activity was independently associated with longer procedures (B = -461.90 (95% CI: -166.34 to -757.46), p = 0.002), use of cardiopulmonary bypass (B = -262.04 (95% CI: -485.68 to -38.39), p = 0.022), the number of administered red cell-concentrates (B = -40.99 (95% CI: -67.86 to -14.12), p = 0.003) and older age (B = -9.35 (95% CI: -16.04 to -2.66), p = 0.006). CONCLUSION: BChE activity is not independently associated with the occurrence of postoperative delirium. Preoperative BChE values are related to patients' morbidity and vulnerability, while postoperative activities reflect the severity, length and complications of surgery.

Predictors of response to intra-arterial vasodilatory therapy of non-occlusive mesenteric ischemia in patients with severe shock: results from a prospective observational study.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI. METHODS: This is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury. RESULTS: A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (interquartile range (IQR)) 0.37 (0.21-0.60) µg/kg/min), elevated lactate concentrations (9.2 (5.2-13) mmol/l) and multi-organ failure. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2-13) mmol/l vs. 24 h: 4.4 (2.5-9.1) mmol/l, p < 0.001) with 22 patients (52.4%) reaching a lactate reduction > 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (hazard ratio 0.409; 95% CI, 0.14-0.631, p = 0.005). CONCLUSIONS: A reduction of lactate concentrations was observed following implementation of intra-arterial therapy, and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration Retrospectively registered on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1 .

Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion.

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.

Chronic Thromboembolic Pulmonary Hypertension Perioperative Monitoring Using Phase-Resolved Functional Lung (PREFUL)-MRI.

BACKGROUND: The translation of phase-resolved functional lung (PREFUL)-MRI to routine practice in monitoring chronic thromboembolic pulmonary hypertension (CTEPH) still requires clinical corresponding imaging biomarkers of pulmonary vascular disease. PURPOSE: To evaluate successful pulmonary endarterectomy (PEA) via PREFUL-MRI with pulmonary pulse wave transit time (pPTT). STUDY TYPE: Retrospective. POPULATION: Thirty CTEPH patients and 12 healthy controls were included. FIELD STRENGTH/SEQUENCE: For PREFUL-MRI a 2D spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence were performed on 1.5T. ASSESSMENT: Eight coronal slices of PREFUL-MRI were obtained on consecutive 13 days before and 14 days after PEA. PREFUL quantitative lung perfusion (PREFULQ ) phases over the whole cardiac cycle were calculated to quantify pPTT, the time the pulmonary pulse wave travels from the central pulmonary arteries to the pulmonary capillaries. Also, perfusion defect percentage based on pPTT (QDPpPTT ), PREFULQ (QDPPREFUL ), and V/Q match were calculated. For DCE-MRI, pulmonary blood flow (PBF) and QDPPBF were computed as reference. For clinical correlation, mean pulmonary arterial pressure (mPAP) and 6-minute walking distance were evaluated preoperatively and after PEA. STATISTICAL TESTS: The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Dice coefficient, and Spearman's correlation coefficient (ρ) were applied. RESULTS: Median pPTT was significantly lower post PEA (139 msec) compared to pre PEA (193 msec), P = 0.0002. Median pPTT correlated significantly with the mPAP post PEA (r = 0.52, P < 0.008). Median pPTT was distributed more homogeneously after PEA: IQR pPTT decreased from 336 to 281 msec (P < 0.004). Median PREFULQ (P < 0.0002), QDPpPTT (P < 0.0478), QDPPREFUL (P < 0.0001) and V/Q match (P < 0.0001) improved significantly after PEA. Percentage change of PREFULQ correlated significantly with percentage change of 6-minute walking distance (ρ = 0.61; P = 0.0031) 5 months post PEA. DATA CONCLUSION: Perioperative perfusion changes in CTEPH can be detected and quantified by PREFUL-MRI. Normalization of pPTT reflects surgical success and improvement of PREFULQ predicts 6-minute walking distance changes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:610-619.

Right-Sided Heart Failure and Extracorporeal Life Support in Patients Undergoing Pericardiectomy for Constrictive Pericarditis: A Risk Factor Analysis for Adverse Outcome.

Background Right ventricular failure is a life-threatening postoperative complication after pericardiectomy. We conducted a retrospective study with a special emphasis on right ventricular failure. Methods Between June 1997 and September 2011, 69 patients underwent surgical pericardiectomy at our center. Mean age was 59 ( ± 15.5) years, and 49 (71%) patients were male. Causes of constrictive pericarditis included idiopathic (52%, n = 36), tuberculosis (9%, n = 6), postcardiotomy (12%, n = 8), radiation (4%, n = 3), renal insufficiency (12%, n = 8), and autoimmune disease (12%, n = 8). Concomitant cardiac surgery was performed in 33 (48%) patients. Results In-hospital mortality rate was 14% (10/69 patients). Extracorporeal membrane oxygenation (ECMO) was necessary in 8 (12%) cases because of right (n = 7) or biventricular (n = 1) failure. Statistical analysis showed a significant correlation between early mortality and the following preoperative variables: postcardiotomy (p = 0.049), radiation (p = 0.009), pleural effusion (p = 0.012), ascites (p = 0.039), hepatic congestion (p = 0.023), absence of calcification on X-ray (p = 0.041), tricuspid valve insufficiency (TI, p < 0.001), and low cardiac index (p = 0.003). Diuretic usage (p = 0.044), peripheral edema (p = 0.050), low voltage (p = 0.027), dip-plateau sign (p = 0.027), elevated GGT (p < 0.001), and decreased serum protein (p < 0.001) correlated with ECMO implantation. Binary logistic regression identified pleural effusion (OR = 16.2, 95% CI = 1.4-191.5), moderate/severe TI (OR = 28.8, 95% CI = 2.7-306.8) and low cardiac index (OR = 25.3, 95% CI = 2.0-315.6) as preoperative independent risk factors for early mortality, whereas elevated GGT (OR = 28.3, 95% CI = 2.4-329.2) and decreased protein (OR = 24.7, 95% CI = 1.8-343.7) could predict right ventricular failure with the need for ECMO. Conclusion We recommend nondelayed ECMO support in case of significant postoperative right-sided heart failure. High-risk patients might benefit from elective pre- or intraoperative ECMO implantation.

Imaging features of primary sarcomas of the great vessels in CT, MRI and PET/CT: a single-center experience.

BACKGROUND: To investigate the imaging features of primary sarcomas of the great vessels in CT, MRI and (18)F-FDG PET/CT. METHODS: Thirteen patients with a primary sarcoma of the great vessels were retrospectively evaluated. All available images studies including F-18 FDG PET(/CT) (n = 4), MDCT (n = 12) and MRI (n = 6) were evaluated and indicative image features of this rare tumor entity were identified. RESULTS: The median interval between the first imaging study and the final diagnosis was 11 weeks (0-12 weeks). The most frequently observed imaging findings suggestive of malignant disease in patients with sarcomas of the pulmonary arteries were a large filling defect with vascular distension, unilaterality and a lack of improvement despite effective anticoagulation. In patients with aortic sarcomas we most frequently observed a pedunculated appearance and an atypical location of the filling defect. The F-18 FDG PET(/CT) examinations demonstrated an unequivocal hypermetabolism of the lesion in all cases (4/4). MRI proved lesion vascularization in 5/6 cases. CONCLUSION: Intravascular unilateral or atypically located filling defects of the great vessels with vascular distension, a pedunculated shape and lack of improvement despite effective anticoagulation are suspicious for primary sarcoma on MDCT or MRI. MR perfusion techniques can add information on the nature of the lesion but the findings may be subtle and equivocal. F-18 FDG PET/CT may have a potential role in these patients and may be considered as part of the imaging workup.

Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia.

Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger-protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery.

Viremia after lung transplant: a cohort study on risk factors and symptoms associated with detection of Epstein-Barr virus.

Background-The frequency and impact of detection of Epstein-Barr virus in the blood of lung and heart-lung transplant recipients in the postoperative period is poorly characterized.Objective-To investigate the frequency of virus detection, associated clinical symptoms and risk factors, and influence of virus detection on outcome.Methods-A cohort of 98 lung transplant recipients were monitored for Epstein-Barr virus in blood before transplant and during their posttransplant hospital stay (median 4 weeks, range 1-21 weeks). Patients were followed up for retransplant or death for a median of 17 months.Results-Epstein-Barr virus DNA was detected in 15 recipients (18.1%) before and in 39 recipients (41.5%) after transplant. Median viral load after transplant was 2300 copies per milliliter of blood (range, 900-45 000 copies/mL). Detection of Epstein-Barr virus DNA before transplant and mechanical ventilation before transplant were associated with detection of Epstein-Barr virus DNA after transplant. Shortness of breath, fatigue, and hoarseness were associated with detection of viral DNA after transplant. The incidence of retransplant or death was not increased in recipients who had viral DNA detected in their blood.Conclusions-Epstein-Barr virus DNA in the blood before transplant and mechanical ventilation before transplant were associated with detection of viral DNA after transplant. Detection of viral DNA after transplant was frequent and clinically relevant.

Stroke, Seizures, Hallucinations and Postoperative Delirium as Neurological Complications after Cardiac Surgery and Percutaneous Valve Replacement.

(1) Background: Neurological complications such as acute ischemic stroke or postoperative delirium are frequent after cardiac surgery or percutaneous valve replacement. This study aimed to identify corresponding risk factors. (2) Methods: 297 patients with percutaneous valve replacement or cardiac surgery were postoperatively screened for neurological complications such as delirium, stroke, seizures and hallucinations twice daily for three days. Pre- and perioperative risk factors were evaluated in a multivariate model. (3) Results: Neurological complications occurred in 43.8% (n = 130) as composed of delirium (43.43%, n = 129), stroke (2.7%, n = 8), seizures (1.35%, n = 4) and real hallucinations (3.36%, n = 10). Multiple logistic regression revealed an association of neurological complications with lower Montreal Cognitive Assessment scores (Exp(B) 2.042; 95% CI, 1.183−3.525, p = 0.010), older age (Exp(B) 1.071; 95% CI, 1.036−1.107, p < 0.001), red blood cell transfusions until postoperative day 3 (Exp(B) 1.157; 95% CI, 1.030−1.300, p = 0.014), history of heart failure (Exp(B) 1.985; 95% CI, 1.130−3.487, p = 0.017) and increased CRP levels (Exp(B) 1.004; 95% CI, 1.000−1.008, p = 0.037). (4) Conclusions: Postoperative delirium remains a frequent complication after cardiac surgery, while stroke and seizures occur rarely. A preoperative risk profile including older age, history of heart failure and cognitive impairment was identified for a complicated postoperative course. However, the impact of an intense inflammatory response must not be neglected.