Relative poverty is associated with increased risk of diabetic ketoacidosis at onset of type 1 diabetes in children. A Swedish national population-based study in 2014-2019.

AIMS: The aim of the study was to estimate the effect of household relative poverty on the risk of diabetic ketoacidosis at diagnosis of children with type 1 diabetes using an international standard measurement of relative poverty. METHODS: A national population-based retrospective study was conducted. The Swedish National Diabetes Register (NDR) was linked with data from Sweden's public statistical agency (Statistics Sweden). Children who were diagnosed with new-onset type 1 diabetes in the period of 2014-2019 were common identifiers. The definition of diabetic ketoacidosis was venous pH <7.30 or a serum bicarbonate level <18 mmol/L. The exposure variable was defined according to the standard definition of the persistent at-risk-of-poverty rate used by the statistical office of the European Union (Eurostat) and several other European public statistical agencies. Univariate and multi-variable analyses were used to calculate the effect of relative poverty on the risk of diabetic ketoacidosis. RESULTS: Children from households with relative poverty had a 41% higher risk of diabetic ketoacidosis (1.41, CI 1.12-1.77, p = 0.004) and more than double the risk of severe diabetic ketoacidosis (pH <7.10) (RR 2.10, CI 1.35-3.25, p = 0.001), as compared to children from households without relative poverty. CONCLUSIONS: Relative poverty significantly increases the risk of diabetic ketoacidosis at onset of type 1 diabetes in children, even in a high-income country with publicly reimbursed health care.

Serum creatinine is an unreliable marker of renal function in patients undergoing heart transplantation.

BACKGROUND: Renal dysfunction is a common complication after heart transplantation (Htx). Glomerular filtration rate (GFR) can be assessed by various estimating equations (eGFR). We evaluated the correlation, agreement, and accuracy between eGFR and mGFR and the ability of eGFR to track changes in mGFR early after Htx. METHODS: A single-center prospective observational study on 55 patients undergoing Htx. Serum creatinine and mGFR (plasma clearance of Cr51-EDTA or iohexol) were measured preoperatively and on the fourth postoperative day. The accuracy of eGFR to predict true mGFR was calculated as the percentage of patients with an eGFR within 30% of mGFR (P30). The agreement between eGFR and mGFR was assessed according to Bland and Altman. A four-quadrant plot was made to evaluate the ability of eGFR to track changes in mGFR. RESULTS: The accuracy of eGFR to assess mGFR was 52%. The bias was 11.2 ± 17.4 mL/min/1.72 m2. The limits of agreement were -23.0 to 45.4 mL/min/1.72 m2 and the error 58%. The concordance rate between eGFR and mGFR was 72%. CONCLUSIONS: eGFR underestimated mGFR and the agreement between eGFR and mGFR was low with an unacceptably large between-group error and low accuracy. Furthermore, the ability of eGFR to assess changes in mGFR, postoperatively, was poor. Thus, the use of estimating equations from serum creatinine will not adequately assess renal function early after major heart surgery. To gain adequate information on renal function early after Htx, GFR needs to be measured, not estimated.

Cardiopulmonary bypass management and acute kidney injury in cardiac surgery patients.

BACKGROUND: Cardiopulmonary bypass (CPB) ensures tissue oxygenation during cardiac surgery. New technology allows continuous registration of CPB variables during the operation. The aim of the present investigation was to study the association between CPB management and the risk of postoperative acute kidney injury (AKI). METHODS: This observational study based on prospectively registered data included 2661 coronary artery bypass grafting and/or valve patients operated during 2016-2020. Individual patient characteristics and postoperative outcomes collected from the SWEDEHEART registry were merged with CPB variables automatically registered every 20 s during CPB. Associations between CPB variables and AKI were analyzed with multivariable logistic regression models adjusted for patient characteristics. RESULTS: In total, 387 patients (14.5%) developed postoperative AKI. After adjustments, longer time on CPB and aortic cross-clamp, periods of compromised blood flow during aortic cross-clamp time, and lower nadir hematocrit were associated with the risk of AKI, while mean blood flow, bladder temperature, central venous pressure, and mixed venous oxygen saturation were not. Patient characteristics independently associated with AKI were advanced age, higher body mass index, hypertension, diabetes mellitus, atrial fibrillation, lower left ventricular ejection fraction, estimated glomerular filtration rate <60 or >90 mL/min/m2 , and preoperative hemoglobin concentration below or above the normal sex-specific range. CONCLUSIONS: To reduce the risk of AKI after cardiac surgery, aortic clamp time and CPB time should be kept short, and low hematocrit and periods of compromised blood flow during aortic cross-clamp time should be avoided if possible.

High-sensitive troponinT, interleukin-8, and interleukin-6 link with post-surgery risk in infant heart surgery.

BACKGROUND: This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. METHODS: Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. RESULTS: Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. CONCLUSIONS: The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.

Atrial natriuretic peptide in the prevention of acute renal dysfunction after heart transplantation-a randomized placebo-controlled double-blind trial.

BACKGROUND: Acute kidney injury (AKI) and renal dysfunction after heart transplantation are common and serious complications. Atrial natriuretic peptide (ANP) has been shown to increase glomerular filtration rate (GFR) and exert renoprotective effects when used for the prevention/treatment of AKI in cardiac surgery. We tested the hypothesis that intraoperative and postoperative administration of ANP could prevent a postoperative decrease in renal function early after heart transplantation. METHODS: Seventy patients were randomized to receive either ANP (50 ng/kg/min) (n = 33) or placebo (n = 37) starting after induction of anesthesia and continued for 4 days after heart transplantation or until treatment with dialysis was started. The primary end-point of the present study was measured GFR (mGFR) at day 4, assessed by plasma clearance of a renal filtration marker. Also, the incidence of postoperative AKI and dialysis were assessed. RESULTS: Median (IQR) mGFR at day 4 postoperatively was 60.0 (57.0) and 50.1 (36.3) ml/min/1.72 m2 for the placebo and ANP groups, respectively (p = .705). During ongoing ANP infusion, the need for dialysis was 21.6% and 9.1% for the placebo and ANP groups, respectively (p = .197). The incidences of AKI for the placebo and the ANP groups were 76.5% and 63.6%, respectively (p = .616). The incidences of AKI stage 1 were 32.4% and 21.2% for the placebo and ANP groups, respectively (p = .420) and for AKI stage 2 or 3, 37.8% and 42.4%, respectively (p = .808). CONCLUSION: The study failed to detect that ANP infusion attenuates renal dysfunction or decreases the incidence of AKI after heart transplantation.

RWMAs in critically ill patients with non-obstructed coronary arteries.

INTRODUCTION: Left ventricular (LV) dysfunction is estimated to occur in 10%-25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population. METHODS: In this retrospective study, data from the hospital angiography register and the ICU register were collated between 2012 and 2019. Patients were identified who underwent angiography in conjunction with their ICU stay and had RWMA on echocardiography. Patients were divided into either those with non-obstructed or those with obstructed coronary arteries. Cardiac magnetic resonance imaging (cMRI) examinations were reviewed if they had been performed on patients with non-obstructed coronaries. RESULTS: We identified 53 patients with RWMA and non-obstructed coronary arteries and 204 patients with RWMA and obstructed coronary arteries. Patients with non-obstructed coronary arteries were more often female, younger, and had fewer cardiovascular risk factors. They less commonly had ST elevation, but more frequently had T-wave inversion or serious arrhythmias. Troponin levels were higher in patients with obstructed coronary arteries, but NT-proBNP was similar between the groups. There were no differences in risk-adjusted 90-day mortality between patients with non-obstructed versus obstructed coronary arteries (OR 1.21, [95% CI 0.56-2.64], p = .628). In those with non-obstructed coronary arteries, follow-up echocardiography was available for 38 patients, of whom 30 showed normalization of cardiac function. Of the 14 patients with non-obstructed coronary arteries on whom cMRI was performed, 7 had a tentative diagnosis of Takotsubo syndrome or myocardial stunning; 4 had a myocardial infarction (preexisting in 3 cases); 1 patient had acute myocarditis; 1 patient had post-myocarditis; and 1 patient was diagnosed with dilated cardiomyopathy. CONCLUSION: RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.

Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease.

INTRODUCTION: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown. METHODS: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit. RESULTS: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies. CONCLUSION: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.

Non-invasive and invasive measurement of skeletal muscular oxygenation during isolated limb perfusion.

BACKGROUND: Isolated limb perfusion (ILP) is a regional surgical treatment for localized metastatic disease. High doses of chemotherapeutic agents are administered within an extracorporeal circulated isolated extremity, treating the metastasis, while systemic toxicity is avoided. To our knowledge, indexed oxygen supply/demand relationship during ILP has not previously been described. Our aim was to measure and describe oxygen metabolism, specifically oxygen delivery, consumption, and extraction, in an isolated leg/arm during ILP. Also investigate whether invasive oxygenation measurement during ILP correlates and can be used interchangeable with the non-invasive method, near infrared spectroscopy (NIRS). METHODS: Data from 40 patients scheduled for ILP were included. At six time points blood samples were drawn during the procedure. DO2, VO2, and O2ER were calculated according to standard formulas. NIRS and hemodynamics were recorded every 10 min. RESULTS: For all observations, the mean of DO2 was 190±59 ml/min/m2, VO2 was 35±8 ml/min/m2, and O2ER was 21±8%. VO2 was significantly higher in legs compared to arms (38±8 vs. 29±7 ml/min/m2, p=0.02). Repeated measures showed a significant decrease in DO2 in legs (209±65 to 180±66 ml/min/m2, p=<0.01) and in arms (252±72 to 150±57 ml/min/m2, p=<0.01). Significant increase in O2ER in arms was also found (p=0.03). Significant correlation was detected between NIRS and venous extremity oxygen saturation (SveO2) (rrm=0.568, p=<. 001, 95% CI 0.397-0.701). When comparing SveO2 and NIRS using a Bland-Altman analysis, the mean difference (bias) was 8.26±13.03 (p=<. 001) and the limit of agreement was - 17.28-33.09, with an error of 32.5%. CONCLUSION: DO2 above 170 ml/min/m2 during ILP kept O2ER below 30% for all observations. NIRS correlates significant to SveO2; however, the two methods do not agree sufficiently to work interchangeable. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT04460053 and NCT03073304.

Dextran-based priming solution during cardiopulmonary bypass attenuates renal tubular injury-A secondary analysis of randomized controlled trial in adult cardiac surgery patients.

BACKGROUND: Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. METHODS: Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. RESULTS: The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p = .038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7 ± 6.3 vs. 2.5 ± 2.7, p = .045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p < .001) compared to the crystalloid group. The incidence of AKI was 18% in the colloid and 22% in the crystalloid group (p = .66). Postoperative serum creatinine did not differ between groups. CONCLUSIONS: In patients undergoing cardiac surgery with CPB, colloid-based priming solution (dextran 40) induced less renal tubular injury compared to a crystalloid-based priming solution. Whether a colloid-based priming solution will improve renal outcome in high-risk cardiac surgery, or not, needs to be evaluated in future studies on higher risk cardiac surgery patients.

Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial.

BACKGROUND: Postoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery. METHODS: Sixty-one elective cardiac surgery patients were randomized to undergo surgery with either a dextran-based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24 h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron-specific enolase (NSE)) and the blood-brain barrier injury marker ß-trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients' age, operation time, and degree of hemolysis. RESULTS: No significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th-75th percentile 327%-702%), NfL +57% (28%-87%), S100B +1145% (783%-2158%), GFAP +17% (-3%-43%), NSE +168% (106%-228%), while ß-trace protein was reduced (-11% (-17-3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24 h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis. CONCLUSION: Uncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood-brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome.

A novel echocardiographic right ventricular dysfunction score can identify hemodynamic severity profiles in left ventricular dysfunction.

PURPOSE: Recognition of congestion and hypoperfusion in patients with chronic left ventricular dysfunction (LVD) has therapeutic and prognostic implications. In the present study we hypothesized that a multiparameter echocardiographic grading of right ventricular dysfunction (RVD) can facilitate the characterization of hemodynamic profiles. METHODS: Consecutive patients (n = 105, age 53 ± 14 years, males 77%, LV ejection fraction 28 ± 11%) referred for heart transplant or heart failure work-up, with catheterization and echocardiography within 48 h, were reviewed retrospectively. Three hemodynamic profiles were defined: compensated LVD (cLVD, normal pulmonary capillary wedge pressure (PCWP < 15 mmHg) and normal mixed venous saturation (SvO2 ≥ 60%)); decompensated LVD (dLVD, with increased PCWP) and LV failure (LVF, increased PCWP and reduced SvO2). We established a 5-point RVD score including pulmonary hypertension, reduced tricuspid annular plane systolic excursion, RV dilatation, ≥ moderate tricuspid regurgitation and increased right atrial pressure. RESULTS: The RVD score [median (IQR 25%;75%)] showed significant in-between the three groups differences with 1 (0;1), 1 (0.5;2) and 3.0 (2;3.5) in patients with cLVD, dLVD and LVF, respectively. The finding of RVD score ≥ 2 or ≥ 4 increased the likelihood of decompensation or LVF 5.2-fold and 6.7-fold, respectively. On the contrary, RVD score < 1 and < 2 reduced the likelihood 11.1-fold and 25-fold, respectively. The RVD score was more helpful than standard echocardiography regarding identification of hemodynamic profiles. CONCLUSIONS: In this proof of concept study an echocardiographic RVD score identified different hemodynamic severity profiles in patients with chronic LVD and reduced ejection fraction. Further studies are needed to validate its general applicability.

Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study.

OBJECTIVE: Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. METHODS: Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. RESULTS: Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). INTERPRETATION: Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382.

Delayed referral is common even when new-onset diabetes is suspected in children. A Swedish prospective observational study of diabetic ketoacidosis at onset of Type 1 diabetes.

OBJECTIVE: Delayed treatment for new-onset diabetes Type 1 (T1D) can lead to diabetic ketoacidosis (DKA) with potentially devastating consequences. This prospective observational study aimed to characterize pediatric patients with DKA at hospital admission, regarding parental awareness of diabetes-related symptoms and delayed referrals from primary health care providers to pediatric emergency wards. RESEARCH DESIGN AND METHODS: Patients 0-18 years admitted to hospital with new-onset T1D and DKA between 2015 and 2017 were invited to participate. Questionnaires were filled out separately by the caregivers and by the attending hospital staff. Data from the Swedish National Diabetes Registry (SWEDIABKIDS) were used for comparison. Delayed referral was defined as a primary healthcare contact due to diabetes-related symptoms 0-4 weeks before hospital admission without immediate referral, or registered elevated glucose levels at primary healthcare centers without immediate referral. RESULTS: The study included 237 patients, among which parental suspicion of new-onset diabetes before healthcare contacts was reported in 39%. Parental suspicion of diabetes was associated with higher pH values at diagnosis. Patients in contact with primary health care providers before hospital admission had a delayed referral in 43% of the cases. Delayed referral was associated with lower pH values at hospital admission. Symptoms leading to primary healthcare contacts were similar regardless of whether delay occurred or not. CONCLUSIONS: Parental suspicion of diabetes was associated with milder DKA at hospital admission. Delayed referral was seen in a considerable proportion of children with primary healthcare contacts for symptoms associated with diabetes. Increased awareness of diabetes symptoms is of paramount importance.

Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery, and current strategies aimed at treating AKI have proven ineffective. Levosimendan, an inodilatating agent, has been shown to increase renal blood flow and glomerular filtration rate in uncomplicated postoperative patients and in patients with the cardiorenal syndrome. We hypothesized that levosimendan through its specific effects on renal vasculature, a preferential vasodilating effect on preglomerular resistance vessels, could improve renal function in AKI-patients with who did not have clinical indication for inotropic support. METHODS: In this single-center, double-blind, randomized controlled study, adult patients with postoperative AKI within 2 days after cardiac surgery, who were hemodynamically stable with a central venous oxygen saturation (ScvO2) ≥ 60% without inotropic support were eligible for inclusion. After randomization, study drug infusions, levosimendan (n = 16) or placebo (n = 13) were given for 5 h. A bolus infusion of levosimendan (12 µg/kg), were given for 30 min followed by 0.1 µg/kg/min for 5 h. Renal blood flow and glomerular filtration rate were measured using infusion clearance of para-aminohippuric acid and a filtration marker, respectively. As a safety issue, norepinephrine was administered to maintain mean arterial pressure between 70-80 mmHg. Intra-group differences were tested by Mann-Whitney U-tests, and a linear mixed model was used to test time and group interaction. RESULTS: Twenty-nine patients completed the study. At inclusion, the mean serum creatinine was higher in the patients randomized to levosimendan (148 ± 29 vs 127 ± 22 µmol/L, p = 0.030), and the estimated GFR was lower (46 ± 12 vs 57 ± 11 ml/min/1.73 m2, p = 0.025). Levosimendan induced a significantly (p = 0.011) more pronounced increase in renal blood flow (15%) compared placebo (3%) and a more pronounced decrease in renal vascular resistance (- 18% vs. - 4%, respectively, p = 0.043). There was a trend for a minor increase in glomerular filtration rate with levosimendan (4.5%, p = 0.079), which did differ significantly from the placebo group (p = 0.440). The mean norepinephrine dose was increased by 82% in the levosimedan group and decreased by 29% in the placebo group (p = 0.012). CONCLUSIONS: In hemodynamically stable patients with AKI after cardiac surgery, levosimendan increases renal blood flow through renal vasodilatation. Trial registration NCT02531724, prospectly registered on 08/20/2015. https://clinicaltrials.gov/ct2/show/NCT02531724?cond=AKI&cntry=SE&age=1&draw=2&rank=1.

Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid ß (Aß1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aß1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aß1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.

Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data.

OBJECTIVES: We compared the effect of two inodilators, levosimendan and milrinone, on the plasma levels of myocardial injury biomarkers, that is, high-sensitivity troponin T and heart-type fatty acid binding protein, and on N-terminal prohormone of brain natriuretic peptide as a biomarker of ventricular function. We hypothesized that levosimendan could attenuate the degree of myocardial injury when compared with milrinone. DESIGN: A post hoc, nonprespecified exploratory secondary analysis of the Milrinone versus Levosimendan-1 trial (ClinicalTrials.gov Identifier: NCT02232399). SETTING: Two pediatric tertiary university hospitals. PATIENTS: Infants 1-12 months old, diagnosed with ventricular septal defect, complete atrioventricular septal defect, or Tetralogy of Fallot undergoing corrective surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy patients received a loading dose of either levosimendan or milrinone at the start of cardiopulmonary bypass followed by an infusion of the respective drug, which continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: Plasma levels of the three cardiac biomarkers were measured prior to the initiation of cardiopulmonary bypass and 2, 6, and 24 hours after weaning from cardiopulmonary bypass. In both groups, the levels of high-sensitivity troponin T and heart-type fatty acid binding protein were highest at 2 hours post cardiopulmonary bypass, whereas the highest level of N-terminal prohormone of brain natriuretic peptide occurred at 24 hours post cardiopulmonary bypass. There was no significant difference in the biomarkers' plasma levels between the study groups over time. Neither was there a significant difference in the postoperative peak plasma levels of the cardiac biomarkers. CONCLUSIONS: In this post hoc analysis of the MiLe-1 trial, there was no demonstrable difference in the postoperative cardiac biomarker profile of myocardial injury and ventricular function when comparing infants managed in the perioperative period with levosimendan versus milrinone.

Atrial natriuretic peptide does not degrade the endothelial glycocalyx: A secondary analysis of a randomized porcine model.

BACKGROUND: The atrial natriuretic peptide (ANP) released from the heart regulates intravascular volume and is suspected to increase capillary permeability. Contradictory results regarding ANP and glycocalyx degradation have been reported. The aim of this study was to investigate if an infusion of ANP causes degradation of the endothelial glycocalyx. METHODS: Twenty pigs, pretreated with 250 mg methylprednisolone, were randomized to receive an infusion of either ANP (50 ng/kg/min) (n = 10) or 0.9% NaCl (n = 10) during 60 min. Endothelial glycocalyx components (heparan sulphate proteoglycan and hyaluronic acid), Hct, calculated plasma volume and colloid osmotic pressure were measured from baseline to 60 min. RESULTS: There was no difference between the control and intervention groups for heparan sulphate proteoglycan and hyaluronic acid corrected for the change in plasma volume (P = .333 and 0.197). Hct increased with 1.8 ± 2.2% in the intervention group (P = .029) with no change -0.5 ± 2.3% in the control group (P = .504). The plasma volume decreased in the intervention group with -8.4 ± 10% (P = .034) with no change in the control group 3.1 ± 12% (P = .427). Median changes in colloid osmotic pressures in the control and intervention group were -0.39 [95% CI, -1.88-0.13] and 0.9 [95% CI, 0.00-1.58], respectively (P = .012). CONCLUSIONS: In this randomized porcine study, an ANP infusion did not cause endothelial glycocalyx degradation but decreased the plasma volume most probably due to precapillary vasodilation and increased filtration.

Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx-A randomized trial.

BACKGROUND: Arterial haematocrit (Hct) has been shown to decrease after anaesthesia induction, most probably because of an increased plasma volume (PV). The primary objective was to quantify change in PV if mean arterial pressure (MAP) was kept at baseline level or allowed to decrease to 60 mm Hg. Our secondary objective was to evaluate underlying mechanisms of this response. METHODS: Twenty-four coronary artery bypass patients were randomized to a higher (90 mm Hg, intervention group) or lower (60 mm Hg, control group) MAP by titration of norepinephrine. During the experimental procedure, no fluids were administered. Baseline PV was measured by 125 I-albumin and the change in PV was calculated from the change in Hct. Changes in MAP, plasma 125 I-albumin, colloid osmotic pressure, albumin, Mid Regional-pro Atrial Natriuretic Peptide (MR-proANP) and endothelial glycocalyx components were measured from baseline to 50 minutes after anaesthesia induction. RESULTS: The MAP during the trial was 93 ± 9 mm Hg in the intervention group and 62 ± 5 mm Hg in the control group. PV increased with up to 420 ± 180 mL in the control group and 45 ± 130 mL in the intervention group (P < .001). Albumin and colloid osmotic pressure decreased significantly more in the control group. MR-proANP increased in the control group but no shedding of the glycocalyx layer was detected in either of the groups. CONCLUSION: Allowing mean arterial pressure to fall to 60 mm Hg during anaesthesia induction, increases the plasma volume due to reabsorption of interstitial water, with no ANP-induced degradation of the endothelial glycocalyx.

Validation of the Nottingham Hip Fracture Score (NHFS) for the prediction of 30-day mortality in a Swedish cohort of hip fractures.

BACKGROUND: Hip fracture is a common osteoporotic fracture with great morbidity and mortality. The utility of ASA classification is limited, as most patients are ≥ASA 3. A reliable predictor of mortality risk could support decision-making. We aimed to evaluate Nottingham hip fracture score (NHFS) for the prediction of 30-day mortality and then to recalibrate the formula converting NHFS to risk of 30-day mortality. METHODS: All patients >60 years with surgically treated hip fracture surgery during 2015-16 were assessed. Data was extracted manually from routinely collected clinical data in registry and medical records. Discriminative performance of NHFS and ASA was assessed with C-statistics. The conversion formula from NHFS to risk of 30-day mortality was recalibrated using logistic binominal regression. Observed vs expected ratios of 30-day mortality were compared with the 2012 NHFS-formula and recalibration was performed in a split dataset. RESULTS: 1864 patients were included, with 213 deaths within 30 days. C-statistic were 0.64 for NHFS and 0.62 for ASA. Comparing expected values from the 2012-revision with our observed deaths gave a ratio of 1.37. Relating predicted levels of 30-day mortality based on 70% of our cohort vs. 30% test portion of our Swedish dataset gave a ratio of 0.97. DISCUSSION: NHFS underestimated mortality in our cohort and showed poor discrimination. Revision of the formula based on a split dataset improved calibration. We suggest NHFS to be routinely implemented to support clinical judgements, expand preoperative assessment and escalate intraoperative monitoring.

Myocardial, renal and intestinal injury in liver resection surgery-A prospective observational pilot study.

BACKGROUND: Post-operative organ complications in liver resection surgery are not uncommon. This prospective observational pilot study was performed to evaluate the incidence, degree and timing of myocardial, renal and intestinal injury in patients undergoing liver resection surgery using the low central venous pressure (LCVP) technique and the Pringle manoeuvre. METHODS: Blood samples were obtained before, during and after elective liver resection until post-operative day (POD) 5. High-sensitive troponin T (hs-TnT), serum creatinine, urea, intestinal fatty acid binding protein (I-FABP), D-lactate, arterial lactate, portal lactate, amylase, as well as urine N-acetyl-ß-D-glucosaminidase (NAG) were analysed. Systemic haemodynamics were measured intraoperatively. RESULTS: Eighteen patients fulfilled the protocol. The Pringle manoeuvre was used in all but 1 patient. hs-TnT increased significantly over time (P < .001) and 5 patients (28%) developed myocardial injury. Five patients had a pre-operative elevation of hs-TnT, four of those developed myocardial injury. Serum creatinine increased significantly over time (P = .015). Acute kidney injury (AKI) occurred in 5 patients (28%), while NAG, as a marker of tubular injury, was not affected. I-FABP increased over time (P < .001) with a maximal 75% increase at 3 hours after resection. D-lactate was below detection level at all measuring points. CONCLUSIONS: In patients undergoing liver resection surgery, using LCVP technique and Pringle manoeuvre, myocardial injury was seen in approximately 30% of the patients post-operatively and almost 30% developed transient AKI in the early post-operative period with no tubular injury. Furthermore, a transient increase of the enterocyte damage marker I-FABP was demonstrated with no signs of gut barrier dysfunction.