Transcatheter Aortic Valve Implantation in Low-Risk Tricuspid or Bicuspid Aortic Stenosis: The NOTION-2 Trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤ 75 years of age, including both tricuspid and bicuspid AS. METHODS: The NOTION-2 trial enrolled and 1:1 randomized low-risk patients aged ≤ 75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke or rehospitalization (related to the procedure, valve or heart failure) at 12 months. RESULTS: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group (absolute risk difference 3.1%; 95% confidence interval [CI], -2.7% to 8.8%; hazard ratio (HR) 1.4, 95% CI: 0.7 to 2.9; p=0.3). Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation and moderate-or-greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0, 95% CI: 0.5 to 2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8, 95% CI: 0.8 to 18.5) treated with TAVI or surgery, respectively (P for interaction=0.1). CONCLUSIONS: Among low-risk patients aged ≤ 75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at one year was similar between TAVI and surgery. TAVI outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134).

Diaphragmatic dysfunction is associated with postoperative pulmonary complications and phrenic nerve paresis in patients undergoing thoracic surgery.

PURPOSE: We aimed to quantify perioperative changes in diaphragmatic function and phrenic nerve conduction in patients undergoing routine thoracic surgery. METHODS: A prospective observational study was performed in patients undergoing esophageal resection or pulmonary lobectomy. Examinations were carried out the day prior to surgery, 3 days and 10-14 days after surgery. Endpoints for diaphragmatic function included ultrasonographic measurements of diaphragmatic excursion and thickening fraction. Endpoints for phrenic nerve conduction included baseline-to-peak amplitude, peak-to-peak amplitude, and transmission delay. Measurements were assessed on both the surgical side and the non-surgical side of the thorax. RESULTS: Forty patients were included in the study. Significant reductions in diaphragmatic excursion were seen on the surgical side of the thorax for all excursion measures (posterior part of the right hemidiaphragm, p < 0.001; hemidiaphragmatic top point, p < 0.001; change in intrathoracic area, p < 0.001). Significant changes were seen for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.041) on the surgical side. However, significant changes were also seen on the non-surgical side for all phrenic nerve measures (baseline-to-peak amplitude, p < 0.001; peak-to-peak amplitude, p < 0.001; transmission delay, p = 0.022). A postoperative reduction in posterior diaphragmatic excursion of more than 50% was significantly associated with postoperative pulmonary complications (coefficient: 2.69 (95% CI [1.38, 4.01], p < 0.001). CONCLUSION: Thoracic surgery caused a significant unilateral reduction in diaphragmatic excursion on the surgical side of the thorax, which was accompanied by significant changes in phrenic nerve conduction. However, phrenic nerve conduction was also significantly affected on the non-surgical side to a lesser extent, which was not mirrored in diaphragmatic excursion. Our findings suggest that phrenic nerve paresis plays a role in postoperative diaphragmatic dysfunction, which may be a contributing factor in the pathogenesis of postoperative pulmonary complications. CLINICAL TRIALS REGISTRATION NUMBER: NCT04507594.

Complication rates rise with age and Haller index in minimally invasive correction of pectus excavatum: A high-volume, single-center retrospective cohort study.

OBJECTIVES: The study objectives were to describe the compounded complication rate of minimally invasive repair of pectus excavatum, identify predisposing risk factors, and evaluate the optimal timing of correction. Minimally invasive repair of pectus excavatum is the standard treatment for pectus excavatum and consists of 2 invasive procedures, for example, correction with bar insertion followed by bar removal after 2 to 3 years. METHODS: A retrospective cohort study identifying children, adolescents, and adults of both genders corrected for pectus excavatum with minimally invasive repair of pectus excavatum between 2001 and 2022. Information on complications related to bar insertion and removal procedures for each individual patient was compiled into a compounded complication rate. Complication severities were categorized according to the Clavien-Dindo classification. RESULTS: A total of 2013 patients were corrected by minimally invasive repair of pectus excavatum with a median age (interquartile range) for correction of 16.6 (5) years. Overall compounded complication rate occurred at a frequency of 16.4%, of which 9.3% required invasive reinterventions (Clavien-Dindo classification ≥IIIa). The complication rate related to bar insertion was 2.6-fold higher compared with bar removal (11.8% vs 4.5%, respectively). Multivariable analysis revealed age (adjusted odds ratio, 1.05; P < .001), precorrection Haller Index (adjusted odds ratio, 1.10; P < .033), and early-phase institutional experience (adjusted odds ratio, 1.59; P < .002) as independent predisposing risk factors. The optimal age of correction was 12 years, and the compounded complication rate correlated exponentially with age with a doubling time of 7.2 years. Complications increased 2.2-fold when the Haller index increased to 5 or more units. CONCLUSIONS: Minimally invasive repair of pectus excavatum is associated with a high compounded complication rate that increases exponentially with age and high Haller Index. Consequently, we recommend repair during late childhood and early adolescence, and emphasize the importance of informing patients and relatives about the significant risks of adult correction as well as the need of 2 consecutive procedures taking the complication profile into account before planning surgery.

Prehospital point-of-care ultrasound in ruptured abdominal aortic aneurysms-a retrospective cohort study.

BACKGROUND: Patients with ruptured abdominal aortic aneurysm (rAAA) require immediate vascular treatment to survive. The use of prehospital point-of-care ultrasound (POCUS) may support clinical assessment, correct diagnosis, appropriate triage and reduce system delay. The aim was to study the process of care and outcome in patients receiving prehospital POCUS versus patients not receiving prehospital POCUS in patients with rAAA, ruptured iliac aneurysm or impending aortic rupture. METHODS: We performed a retrospective cohort study in patients diagnosed with rAAA in the Central Denmark Region treated by a prehospital critical care physician from 1 January 2017 to 31 December 2021. Performance of prehospital POCUS was extracted from the prehospital electronic health records. System delay was defined as the time from the emergency phone call to the emergency medical service dispatch centre until the start of surgery. Data on patients primary hospital admission to a centre with/without vascular treatment expertise, treatments and complications including death were extracted from electronic health records. RESULTS: We included 169 patients; prehospital POCUS was performed in 124 patients (73%). Emergency surgical treatment was performed in 71 patients. The overall survival in the POCUS group was 39% versus 16% in the NO POCUS group (hazard ratio (HR) (95% 0.60, 95% CI: 0.41-0.89, p = .011). In the POCUS group 99/124 (80%) were directly admitted to a vascular surgical centre versus 25/45 (56%) in the NO POCUS, RD 24% (95% CI: 8-40)), (p = .002). In the POCUS group, system delay was a median of 142 minutes (interquartile range (IQR) 121-189) and a median of 232 minutes (IQR 166-305) in the NO POCUS group (p = .006). In a multivariable analysis incorporating age, sex, previously known rAAA, and typical clinical symptoms of rAAA, the HR for death was 0.57, 95% CI 0.38-0.86 (p = .008) favouring prehospital POCUS. CONCLUSIONS: Prehospital POCUS was associated with reduced time to treatment, higher chance of operability and significantly higher 30-day survival in patients with rAAA, ruptured iliac aneurysm or impending rupture of an AAA in this retrospective study. Residual confounding cannot be excluded. This study supports the clinical relevance of prehospital POCUS of the abdominal aorta.

The effects of respiratory rate and tidal volume on pulse pressure variation in healthy lungs-a generalized additive model approach may help overcome limitations.

Pulse pressure variation (PPV) is a well-established method for predicting fluid responsiveness in mechanically ventilated patients. The predictive accuracy is, however, disputed for ventilation with low tidal volume (VT) or low heart-rate-to-respiratory-rate ratio (HR/RR). We investigated the effects of VT and RR on PPV and on PPV's ability to predict fluid responsiveness. We included patients scheduled for open abdominal surgery. Prior to a 250 ml fluid bolus, we ventilated patients with combinations of VT from 4 to 10 ml kg-1 and RR from 10 to 31 min-1. For each of 10 RR-VT combinations, PPV was derived using both a classic approach and a generalized additive model (GAM) approach. The stroke volume (SV) response to fluid was evaluated using uncalibrated pulse contour analysis. An SV increase > 10% defined fluid responsiveness. Fifty of 52 included patients received a fluid bolus. Ten were fluid responders. For all ventilator settings, fluid responsiveness prediction with PPV was inconclusive with point estimates for the area under the receiver operating characteristics curve between 0.62 and 0.82. Both PPV measures were nearly proportional to VT. Higher RR was associated with lower PPV. Classically derived PPV was affected more by RR than GAM-derived PPV. Correcting PPV for VT could improve PPV's predictive utility. Low HR/RR has limited effect on GAM-derived PPV, indicating that the low HR/RR limitation is related to how PPV is calculated. We did not demonstrate any benefit of GAM-derived PPV in predicting fluid responsiveness.Trial registration: ClinicalTrials.gov, reg. March 6, 2020, NCT04298931.

Perioperative anaesthesia by local infiltration following median sternotomy - a study protocol.

INTRODUCTION: Post-operative pain following open heart surgery is a clinical challenge usually requiring significant amounts of opioids. Long-acting local infiltration anaesthesia may effectively reduce post-operative opioid consumption and improve recovery. The trial is a publicly funded, double-blinded, randomised, placebo-controlled trial evaluating the effect of long-acting local infiltration anaesthesia in open heart surgery. METHODS: Two Danish centres are planning to randomise 100 patients undergoing coronary artery bypass grafting to treatment with long-acting infiltration anaesthesia or placebo. We compare an active solution of bupivacaine, adrenaline, clonidine and dexamethasone with saline placebo. The primary outcome measure is the accumulated opioid use within the first 24 post-operative hours. Secondary outcome measures include evaluation of respiratory function, patient-reported pain scores, mobilisation, opioid-associated side effects and long-term opioid consumption. CONCLUSION: This trial will define whether the use of long-acting infiltration anaesthesia during heart surgery may reduce acute and prolonged post-operative opioid consumption. Reduction of opioid-related adverse effects may improve recovery. FUNDING: The trial is supported by public grants (Dansk Selskab for Anæstesiologi og Intensiv Medicin: 40,000 DKK; Regionernes Medicin og Behandlingspulje 2022: 686,000 DKK). The work of I. S. Modrau is supported by an unrestricted grant from the Health Research Foundation of the Central Denmark Region. TRIAL REGISTRATION: EudraCT 2021-005886-41.

Individualised perioperative blood pressure and fluid therapy in oesophagectomy ­ study protocol for a randomised clinical trial

INTRODUCTION: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient's own night-time blood pressure as the lower threshold. METHODS: This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery. CONCLUSIONS: The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients. FUNDING: The trial is supported by Aarhus University (1,293,400 DKK) and the Novo Nordisk Foundation (625,200 DKK). TRIAL REGISTRATION: EudraCT number: 2021-002816-30.

The haemodynamic effects of phenylephrine after cardiac surgery.

BACKGROUND: Phenylephrine increases systemic- and pulmonary resistances and therefore may increase blood pressures at the expense of blood flow. Cardio-pulmonary bypass alters vasoreactivity and many patients exhibit chronotropic insufficiency after cardiac surgery. We aimed to describe the haemodynamic effects of phenylephrine infusion after cardiac surgery. METHODS: Patients in steady state after low-risk cardiac surgery received incremental infusion rates of phenylephrine up to 1.0 µg/kg/min with the aim of increasing systemic mean arterial blood pressure 20 mmHg. Invasive haemodynamic parameters, including pulmonary wedge pressures, were captured along with echocardiographic measures of biventricular function before, during phenylephrine infusion at target systemic blood pressure, and 20 min after phenylephrine discontinuation. RESULTS: Thirty patients were included. Phenylephrine increased mean arterial pressure increased from 78 (±9) mmHg to 98 (±10) mmHg with phenylephrine infusion. Also, pulmonary blood pressure as well as systemic- and pulmonary resistances increased. The ratio between systemic- and pulmonary artery resistances did not change statistically significantly (p = .59). Median cardiac output was 4.35 (interquartile range [IQR] 3.6-5.4) L/min at baseline and increased significantly with phenylephrine infusion (median Δcardiac output was 0.25 [IQR 0.1-0.6] L/min) (p = .012). Pulmonary artery wedge pressure increased from 10.2 (±3.0) mmHg to 11.9 (±3.4) mmHg (p < .001). This was accompanied by significant increases in central venous pressure. Phenylephrine infusion increased left ventricular end-diastolic volume from 105 (±46) mL to 119 (±44) mL (p < .001). All results of phenylephrine infusion were reversed with discontinuation. CONCLUSION: In haemodynamically stable patients after cardiac surgery, phenylephrine increased PVR and SVR, but did not change the PVR/SVR ratio. Phenylephrine increased biventricular filling pressures and left ventricular end-diastolic area. Consequently, CO increased as ejection fraction was maintained. These findings do not discourage the use of phenylephrine after low-risk cardiac surgery. REGISTRATION: clinicaltrial.gov (identifier NCT04419662).

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-saving.

Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics.

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤-5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.

Impact of national holidays and weekends on incidence of acute type A aortic dissection repair.

Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54-0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68-0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.

The effects of preoperative focused cardiac ultrasound in high-risk patients: A randomised controlled trial (PREOPFOCUS).

BACKGROUND: Surgery is the third most common cause of mortality worldwide. Focused cardiac ultrasound (FOCUS) yields information on cardiac status and discloses the presence of unknown pathology. Preoperative FOCUS changes patient treatment, allowing for a patient-tailored anaesthesia. We hypothesised that preoperative FOCUS would reduce the proportion of patients who were either admitted to hospital for more than 10 days or who were dead within 30 days after high-risk, non-cardiac surgery. METHODS: This was a randomised, controlled, multi-center study. Patients ≥65 years of age, admitted for urgent orthopaedic- or abdominal surgery, scheduled for general- or neuraxial anaesthesia and with ASA 3/4 were eligible for inclusion. Patients were randomised in a 1:1 ratio to preoperative FOCUS or no preoperative FOCUS performed in accordance with a predefined protocol. Primary endpoint was the proportion of patients admitted more than 10 days or who were dead within 30 days. Secondary endpoints included major complications, days of admission and changes in anaesthesia handling. RESULTS: During the second COVID-19 wave the study monitoring committee terminated the study prematurely. We included 338 patients of which 327 were included in the final analysis. In the FOCUS group, 41/163 (25%) patients met the criteria for the primary endpoint versus 35/164 (21%) for the control group, adjusted odds ratio 1.37 (95% CI 0.86-2.30), p = .36. The proportions of patients who developed major complications did not differ significantly between groups. Length of hospital stay was 4 (3-8) days in the FOCUS group and 4 (3-7) days on the control group (adjusted p = .24). CONCLUSION: The routine availability of preoperative FOCUS assessment in this cohort does not appear to reduce the risk for hospitalisation exceeding 10 days or 30-day mortality, although study enrolment was prematurely terminated.

Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients: 5-Year Outcomes of the SURTAVI Randomized Clinical Trial.

Importance: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective: To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants: SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention: Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures: The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results: A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance: Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Epidural analgesia and abnormal coagulation in patients undergoing minimal invasive repair of pectus excavatum.

Background: Epidural analgesia (EA) is effective in patients undergoing minimal invasive repair of pectus excavatum (MIRPE) but is associated with major complications such as epidural hematomas. It is recommended to assess coagulation status in patients receiving anticoagulant therapy prior to EA, although no consensus exists in patients without a history of bleeding tendency or anticoagulant therapy. Thus, the aim of this paper was to assess 1) the prevalence of abnormal routine coagulation parameters, i.e., international normalized ratio (INR) and platelet count, and 2) the safety of EA in patients undergoing MIRPE. Methods: In this retrospective study, we identified 1,973 patients undergoing MIRPE at our center between 2001 and 2019. Complications related to EA were registered for all patients. Information on coagulation parameters was present in 929 patients. Patients with spontaneously elevated INR ≥1.5 were referred for assessment of coagulation factor VII in order to assess the cause of the elevated INR. Results: Of 929 patients with coagulation information available, 18 patients had spontaneously elevated INR ≥1.5 (1.9%). In patients with INR ≥1.5, 12 patients underwent further assessment of factor VII, with all patients having a slightly reduced factor VII close to the lower reference range. The majority of the 1,973 patients undergoing MIRPE received EA (99.6%) with very low complication rates (0.2%) and no incidence of epidural hematomas. Conclusion: In patients undergoing MIRPE, coagulation screening prior to EA should not be mandatory as it revealed no clinically relevant consequences. EA is safe with very low complication rates.

Effects of changes in position, positive end-expiratory pressure and mean arterial pressure on renal, portal and hepatic Doppler ultrasound perfusion indices: a randomized crossover study in cardiac surgery patients.

Point-of-care ultrasound perfusion indices can be used for detection of AKI and venous congestion. Patients in the postoperative- and intensive care units are frequently exposed to alternating treatment and loading conditions. We aimed to study the effects of changes in preload (patient positioning), positive end-expiratory pressure (PEEP) and afterload (phenylephrine) on renal, portal and hepatic ultrasound indices. We hypothesized that renal resistive index was not influenced by changes in PEEP and patient positioning. This was a single-site, randomized, crossover study. Patients above 18 years scheduled for elective open-heart surgery at Aarhus University Hospital, Denmark, were available for inclusion. Patients were randomized to a sequence of six combinations of PEEP and position in addition to an increase in mean arterial pressure by phenylephrine. Thirty-one patients participated in the study. Resistive index was influenced by positional change (P = 0.007), but not by change in PEEP (P = 0.50) (Table 1). Renal venous stasis index and portal pulsatility fraction increased in the raised legs position (P ≤ 0.019), but not with increases in PEEP. Renal venous flow pattern and hepatic venous flow pattern were affected by position (P ≤ 0.019), but not by PEEP. None of the ultrasound indices were significantly changed by infusion of phenylephrine. Doppler perfusion indices were significantly affected by changes in preload, but not by changes in PEEP or afterload. Although the changes in the Doppler ultrasound indices were significant, they were small in absolute numbers. Therefore, from a clinical perspective, the ultrasound indices were robust.Trial registration Registered at clinicaltrials.com, first posted online June 5th 2020, identifier: NCT04419662.

Tolerable Duration of Warm Ischaemia After Circulatory Death Is Safe For At Least One Hour in Porcine Lungs: Functional Assessment with Ex Vivo Lung Perfusion.

BACKGROUND: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP). METHODS: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score. RESULTS: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed. CONCLUSION: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.

Topical Brimonidine Delays Ultraviolet Radiation-Induced Squamous Cell Carcinoma in Hairless Mice.

We investigated whether topical brimonidine delayed or enhanced the development of squamous cell carcinoma (SCC) when ultraviolet radiation (UVR) was applied to a well-established murine model. Hairless female mice (n = 125) were randomized into five groups and treated as follows: 1% brimonidine cream before UVR (Group 1), 0.33% brimonidine gel before UVR (Group 2), 1% brimonidine cream after UVR (Group 3), UVR only (control; Group 4) and 1% brimonidine cream only (control; Group 5). For each animal, the first four tumors were recorded and followed until three tumors reached 4 mm or one tumor reached 12 mm in diameter. All animal experiments continued for up to 365 days or until death. Application of 1% brimonidine cream before UVR delayed tumor development relative to control mice treated with UVR alone (P = 0.000006). However, when 0.33% brimonidine gel was applied before UVR (P = 0.313) or 1% brimonidine cream was applied after UVR (P = 0.252), there was no significant delay in tumor development relative to control mice treated with UVR alone. The development of the second and third tumors followed a similar pattern. Topical 1% brimonidine cream applied before UVR exposure delayed SCC development in hairless mice. In contrast, when brimonidine was applied after UVR there was no significant delay in tumor development. These results suggest that the 1% brimonidine cream probably absorbed the UVR, and therefore, a delay in tumor formation was only seen when brimonidine was applied before irradiation. However, there can be multiple reasons for this delay in photocarcinogenesis.

Once after a full moon: acute type A aortic dissection and lunar phases.

OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period). RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated. CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.

Ultrasound Hepatic Vein Ratios Are Associated With the Development of Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: The authors investigated the use of hepatic venous and right-heart ultrasound parameters in predicting cardiac surgery-associated acute kidney injury (AKI). DESIGN: This was a prospective, contextual, descriptive two-center study. Blood tests,clinical and ultrasound data were obtained preoperatively, and postoperative day one, and day four. The hepatic vein, inferior vena cava, and right-heart Doppler ultrasound parameters were obtained and analyzed. SETTING: The sites of the study were Johannesburg, South Africa, and Aarhus, Denmark. PARTICIPANTS: Adult patients who satisfied inclusion criteria, between August 2019 and January 2020, were included, with a total of 152 participants. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range) age of patients was 68 (55-73) years, predominantly male, and the majority were hypertensive. Of 152 patients analyzed, 54 (35%) patients developed AKI. Among these, 37 (69%) were classified as Kidney Disease: Improving Global Outcomes (KDIGO) stage I, 11 (20%) as stage II, while six (11%) were stage III. Age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.00-1.10 p = 0.031), The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (AOR 1.43, 95% CI 1.14-1.80, p = 0.005], and preoperative serum creatinine (AOR 1.04, 95% CI 1.01-1.08, p = 0.013) were predictive of AKI. Those who developed AKI had experienced longer cardiopulmonary bypass (CPB) times (p < 0.001). Preoperatively, hepatic vein S-wave measurements were significantly higher in patients with AKI (p < 0.05). On postoperative day one (D1), the hepatic vein flow ratios of patients with AKI were significantly decreased, driven by low S waves and high D waves, and accompanied by significantly elevated central venous pressure (CVP) levels. CVP levels on D1 postoperatively were predictive of AKI (AOR 1.31, 95% CI 1.11-1.55, p = 0.001). Measurements of right ventricular (RV) base, tricuspid annular plane excursion (TAPSE), and inferior vena cava were not associated with the development of AKI (p > 0.05). CONCLUSION: There was an association between the development of AKI and a decrease in hepatic flow ratios on D1, driven by low S-wave and high D-wave velocities. The presence of venous congestion was reflected by significantly elevated CVP values, which were independently associated with AKI on D1. RV base and TAPSE measurements were, however, not associated with AKI. These parameters may reflect perioperative circumstances, including prolonged CPB times and potential fluid management, which can be modified in this period.