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.

Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb): Protocol for a Multicenter Clinical Randomized Controlled Trial.

BACKGROUND: Lung transplantation (LTx) is the only treatment option for end-stage lung disease. Despite improvements, primary graft dysfunction (PGD) remains the leading cause of early mortality and precipitates chronic lung allograft dysfunction, the main factor in late mortality after LTx. PGD develops within the first 72 hours and impairs the oxygenation capacity of the lung, measured as partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2). Increasing the PaO2/FiO2 ratio is thus critical and has an impact on survival. There is a general lack of effective treatments for PGD. When a transplanted lung is not accepted by the immune system in the recipient, a systemic inflammatory response starts where cytokines play a critical role in initiating, amplifying, and maintaining the inflammation leading to PGD. Cytokine filtration can remove these cytokines from the circulation, thus reducing inflammation. In a proof-of-concept preclinical porcine model of LTx, cytokine filtration improved oxygenation and decreased PGD. In a feasibility study, we successfully treated patients undergoing LTx with cytokine filtration (ClinicalTrials.gov; NCT05242289). OBJECTIVE: The purpose of this clinical trial is to demonstrate the superiority of cytokine filtration in improving LTx outcome, based on its effects on oxygenation ratio, plasma levels of inflammatory markers, PGD incidence and severity, lung function, kidney function, survival, and quality of life compared with standard treatment with no cytokine filtration. METHODS: This study is a Swedish national interventional randomized controlled trial involving 116 patients. Its primary objective is to investigate the potential benefits of cytokine filtration when used in conjunction with LTx. Specifically, this study aims to determine whether the application of cytokine filtration, administered for a duration of 12 hours within the initial 24 hours following a LTx procedure, can lead to improved patient outcomes. This study seeks to assess various aspects of patient recovery and overall health to ascertain the potential positive impact of this intervention on the posttransplantation course. RESULTS: The process of patient recruitment for this study is scheduled to commence subsequent to a site initiation visit, which was slated to take place on August 28, 2023. The primary outcome measure that will be assessed in this research endeavor is the oxygenation ratio, a metric denoted as the highest PaO2/FiO2 ratio achieved by patients within a 72-hour timeframe following their LTx procedure. CONCLUSIONS: We propose that cytokine filtration could enhance the overall outcomes of LTx. Our hypothesis suggests potential improvements in LTx outcome and patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05526950; https://www.clinicaltrials.gov/study/NCT05526950. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52553.

Cardiopulmonary bypass management and risk of new-onset atrial fibrillation after cardiac surgery.

OBJECTIVES: Cardiopulmonary bypass (CPB) management may potentially play a role in the development of new-onset atrial fibrillation (AF) after cardiac surgery. The aim of this study was to explore this potential association. METHODS: Patients who underwent coronary artery bypass grafting and/or valvular surgery during 2016-2020 were included in an observational single-centre study. Data collected from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry and a local CPB database were merged. Associations between individual CPB variables (CPB and aortic clamp times, arterial and central venous pressure, mixed venous oxygen saturation, blood flow index, bladder temperature and haematocrit) and new-onset AF were analysed using multivariable logistic regression models adjusted for patient characteristics, comorbidities and surgical procedure. RESULTS: Out of 1999 patients, 758 (37.9%) developed new-onset AF. Patients with new-onset postoperative AF were older, had a higher incidence of previous stroke, worse renal function and higher EuroSCORE II and CHA2DS2-VASc scores and more often underwent valve surgery. Longer CPB time [adjusted odds ratio 1.05 per 10 min (95% confidence interval 1.01-1.08); P = 0.008] and higher flow index [adjusted odds ratio 1.21 per 0.2 l/m2 (95% confidence interval 1.02-1.42); P = 0.026] were associated with an increased risk for new-onset AF, while the other variables were not. A sensitivity analysis only including patients with isolated coronary artery bypass grafting supported the primary analyses. CONCLUSIONS: CPB management following current guideline recommendations appears to have minor or no influence on the risk of developing new-onset AF after cardiac surgery.

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.

Risk factors and treatment of oxygenator high-pressure excursions during cardiopulmonary bypass.

INTRODUCTION: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. METHODS: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016-2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. RESULTS: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16-1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09-1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26-6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03-7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution (n = 29, 78.4%), and/or extra heparin (n = 23, 62.2%), and/or epoprostenol (n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17-15.57), p = 0.011). CONCLUSIONS: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.

Prehospital monitoring of cerebral circulation during out of hospital cardiac arrest ? A feasibility study.

BACKGROUND: About two-thirds of the in-hospital deaths after out-of-hospital cardiac arrests (OHCA) are a consequence of anoxic brain injuries, which are due to hypoperfusion of the brain during the cardiac arrests. Being able to monitor cerebral perfusion during cardiopulmonary resuscitation (CPR) is desirable to evaluate the effectiveness of the CPR and to guide further decision making and prognostication. METHODS: Two different devices were used to measure regional cerebral oxygen saturation (rSO2): INVOS™ 5100 (Medtronic, Minneapolis, MN, USA) and Root® O3 (Masimo Corporation, Irvine, CA, USA). At the scene of the OHCA, advanced life support (ALS) was immediately initiated by the Emergency Medical Services (EMS) personnel. Sensors for measuring rSO2 were applied at the scene or during transportation to the hospital. rSO2 values were documented manually together with ETCO2 (end tidal carbon dioxide) on a worksheet specially designed for this study. The study worksheet also included a questionnaire for the EMS personnel with one statement on usability regarding potential interference with ALS. RESULTS: Twenty-seven patients were included in the statistical analyses. In the INVOS™5100 group (n = 13), the mean rSO2 was 54% (95% CI 40.3-67.7) for patients achieving a return of spontaneous circulation (ROSC) and 28% (95% CI 12.3-43.7) for patients not achieving ROSC (p = 0.04). In the Root® O3 group (n = 14), the mean rSO2 was 50% (95% CI 46.5-53.5) and 41% (95% CI 36.3-45.7) (p = 0.02) for ROSC and no ROSC, respectively. ETCO2 values were not statistically different between the groups. The EMS personnel graded the statement of interference with ALS to a median of 2 (IQR 1-6) on a 10-point Numerical Rating Scale. CONCLUSION: Our results suggest that both INVOS™5100 and ROOT® O3 can distinguish between ROSC and no ROSC in OHCA, and both could be used in the pre-hospital setting and during transport with minimal interference with ALS.

Whole Blood Adsorber During CPB and Need for Vasoactive Treatment After Valve Surgery in Acute Endocarditis: A Randomized Controlled Study.

OBJECTIVES: Patients with endocarditis requiring urgent valvular surgery with cardiopulmonary bypass are at a high risk of developing systemic inflammatory response syndrome and septic shock, necessitating intensive use of vasopressors after surgery. The use of a cytokine hemoadsorber (CytoSorb, CytoSorbents Europe GmbH, Germany) during cardiac surgery has been suggested to reduce the risk of inflammatory activation. The study authors hypothesized that adding a cytokine adsorber would reduce cytokine burden, which would translate into improved hemodynamic stability. DESIGN: A randomized, controlled, nonblinded clinical trial. SETTING: At a university hospital, tertiary referral center. PARTICIPANTS: Nineteen patients with endocarditis undergoing valve surgery. INTERVENTION: A cytokine hemoadsorber integrated into the cardiopulmonary bypass circuit. MEASUREMENTS AND MAIN RESULTS: The accumulated norepinephrine dose in the intervention group was half or less at all postoperative time points compared to the control group, although it did not reach statistical significance; at 24 and 48 hours (median 36 [25-75 percentiles; 12-57] µg v 114 [25-559] µg, p = 0.11 and 36 [12-99] µg v 261 [25-689] µg, p = 0.09). There was no significant difference in chest tube output, but there was a significantly lower need for the transfusion of red blood cells (285 [0-657] mL v 1,940 [883-2,148] mL, p = 0.03). CONCLUSIONS: There was no statistically significant difference between the groups with regard to vasopressor use after surgery for endocarditis with the use of a cytokine hemoadsorber during cardiopulmonary bypass. Additional, larger randomized controlled trials are needed to definitely assess the potential effect.

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.

Cerebral autoregulation in infants during sevoflurane anesthesia for craniofacial surgery.

BACKGROUND: Data on cerebral pressure-flow autoregulation in the youngest children are scarce. We studied the correlation between mean arterial pressure and cerebral tissue oxygen saturation (rSO2 ) by near-infrared spectroscopy (NIRS) in patients undergoing nose, lip, and palate surgery. AIM: We tested the hypothesis that cerebral pressure-flow autoregulation is impaired in children less than 1 year undergoing surgery and general anesthesia with sevoflurane under controlled mechanical ventilation. METHOD: After approval from the Ethical board, 15 children aged <1 year were included. Before anesthesia induction, a NIRS sensor (INVOSTM , Medtronic, Minneapolis, USA) was placed over the cerebral frontal lobe. Frontal rSO2 , a surrogate for cerebral perfusion, mean arterial pressure, end-tidal CO2 - and sevoflurane concentration, and arterial oxygen saturation were sampled every minute after the induction. A repeated measures correlation analysis was performed to study correlation between mean arterial pressure and cerebral rSO2 , and the repeated measures correlation coefficient (rrm ) was calculated. RESULTS: Fifteen patients, aged 7.7 ± 1.9 months, were studied. rSO2 showed a positive correlation with mean arterial pressure ([95% CI: 9.0-12.1], P < 0.001) with a moderate to large effect size (rrm  = 0.462), indicating an impaired cerebral pressure-flow autoregulation. The slopes of the rSO2 -mean arterial pressure correlations were steeper in patients who were hypotensive (mean arterial pressure <50 mm Hg) compared to patients having a mean arterial pressure ≥50 mm Hg, indicating that at lower mean arterial pressure, the cerebral pressure dependence of cerebral oxygenation is even more pronounced. CONCLUSION: During sevoflurane anesthesia in the youngest pediatric patients, cerebral perfusion is pressure-dependent, suggesting that the efficiency of the cerebral blood flow autoregulation is limited.

Renal Hemodynamics, Function, and Oxygenation in Critically Ill Patients and after Major Surgery.

This review outlines the available data from the work of our group on renal hemodynamics, function, and oxygenation in patients who are critically ill with acute renal dysfunction, such as those with postoperative AKI, those in early clinical septic shock, in patients undergoing cardiac surgery with cardiopulmonary bypass, or in patients undergoing liver transplantation. We also provide information on renal hemodynamics, function, and oxygenation in patients with chronic renal impairment due to congestive heart failure. This review will argue that, for all of these groups of patients, the common denominator is that renal oxygenation is impaired due to a lower renal oxygen delivery or a pronounced increase in renal oxygen consumption.

Renal Near-Infrared Spectroscopy for Assessment of Renal Oxygenation in Adults Undergoing Cardiac Surgery: A Method Validation Study.

OBJECTIVE: To investigate the correlation between invasively measured renal venous oxygen saturation (SrvO2) and tissue oxygenation (rSO2) measured with near-infrared spectroscopy (NIRS) in adult patients undergoing cardiac surgery. DESIGN: Prospective observational study. SETTING: Single cardiac surgery center at a university hospital. PARTICIPANTS: Thirteen adult patients with skin- to- kidney distance ≤4 cm undergoing open cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: All patients received renal vein catheters for invasive measurement of SrvO2, and NIRS electrodes for assessment of renal rSO2 were placed over the kidney using ultrasound guidance. Measurements were made before CPB, during CPB at 3 different flow rates (2.4, 2.7, and 3.0 L/min/m2), and after CPB. MEASUREMENTS AND MAIN RESULTS: Repeated- measures correlation analyses and Bland-Altman plots were used to study the correlation and agreement between rSO2 and SrvO2. For all measurement points, renal rSO2 correlated with SrvO2 (rrm = 0.61, p < 0.001), and the mean difference (bias) between rSO2 and SrvO2 was -2.71 ± 7.22 (p = 0.002), with an error of 17.6%. When measurements during CPB and before and after CPB were studied separately, rSO2 and SrvO2 were correlated (rrm = 0.51, p < 0.007 and rrm = 0.73, p < 0.001, respectively). During CPB, renal rSO2 predicted SrvO2 with a bias of -3.41 ± 7.76 (p = 0.009) and an error of 18.8%. Before and after CPB, the mean difference was -1.93 ± 6.60 (p = 0.092), with an error of 16.2%. CONCLUSIONS: Renal rSO2 is correlated to and predicts SrvO2 with a small bias and acceptable agreement. Further studies are needed before renal NIRS can be used as a surrogate marker of renal oxygenation in clinical practice.

Effects of milrinone on renal perfusion, filtration and oxygenation in patients with acute heart failure and low cardiac output early after cardiac surgery.

PURPOSE: Early postoperative heart failure is common after cardiac surgery, and inotrope treatment may impact renal perfusion and oxygenation. We aimed to study the renal effects of the inodilator milrinone when used for the treatment of heart failure after weaning from cardiopulmonary bypass (CPB). MATERIAL AND METHODS: In 26 patients undergoing cardiac surgery with CPB, we used renal vein catheterization to prospectively measure renal blood flow (RBF), glomerular filtration rate (GFR), and renal oxygenation. Patients who developed acute heart failure and low cardiac output (cardiac index <2.1 L/min/m2) at 30 min after weaning from CPB (n = 7) were given milrinone, and the remaining patients (n = 19) served as controls. Additional measurements were made at 60 min after CPB. RESULTS: In patients with acute postoperative heart failure, before receiving milrinone, renal blood flow was lower (-33%, p < .05) while renal oxygen extraction was higher (41%, p < .05) compared to the control group. Milrinone increased cardiac index (21%, p < .001), RBF (36%, p < .01) and renal oxygen delivery (35%, p < .01), with no significant change in GFR and oxygen consumption compared to the control group. CONCLUSIONS: In patients with acute heart failure after weaning from CPB, the milrinone-induced increase in cardiac output was accompanied by improved renal oxygenation. TRIAL REGISTRATION: ClinicalTrials.gov; identifier NCT02405195, date of registration; March 27, 2015, and NCT02549066, date of registration; 9 September 2015.

Impact of Cardiopulmonary Bypass Flow on Renal Oxygenation in Patients Undergoing Cardiac Operations.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with acute kidney injury, and the risk increases with low oxygen delivery during CPB. We hypothesized that renal oxygenation could be improved at higher than normal CPB flow rates. METHODS: After ethical approval and informed consent, 17 patients with normal serum creatinine undergoing normothermic CPB were included and received pulmonary artery and renal vein catheters after anesthesia induction for measurements of systemic and renal variables. Renal oxygen extraction, a direct measure of the renal oxygen delivery/renal oxygen consumption ratio, and renal filtration fraction were measured, the latter by renal extraction of 51chromium-ethylenediaminetetraacetic acid. After start of CPB and aortic cross-clamp, the pump flow rate was randomly varied between 2.4, 2.7, and 3.0 L · min-1 · m-2, and measurements were made after 10 minutes at each flow rate. RESULTS: Renal oxygen extraction increased by 30% at a flow rate of 2.4 L · min-1 · m-2 versus pre-CPB (p < 0.05). At a flow rate of 2.7 and 3.0 L · min-1 · m-2, Renal oxygen extraction was 12% (p < 0.05) and 23% (p < 0.01) lower, respectively, compared with 2.4 L · min-1 · m-2. This corresponds to a 14% and 30% improvement, respectively, of the renal oxygen supply/demand relationship. Filtration fraction was not affected by changes in flow rate, indicating that the glomerular filtration rate increased in proportion to the increase in renal perfusion. CONCLUSIONS: The impaired renal oxygenation seen during CPB is ameliorated by an increase in CPB flow rate. Thus, one way to protect the kidneys during CPB could be to use a higher flow rate than the one traditionally used.

Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double-Blind Controlled Trial.

Background The management of the cardiorenal syndrome in advanced heart failure is challenging, and the role of inotropic drugs has not been fully defined. Our aim was to compare the renal effects of levosimendan versus dobutamine in patients with heart failure and renal impairment. Methods and Results In a randomized double-blind study, we assigned patients with chronic heart failure (left ventricular ejection fraction <40%) and impaired renal function (glomerular filtration rate <80 mL/min per 1.73 m2) to receive either levosimendan (loading dose 12 µg/kg+0.1 µg/kg per minute) or dobutamine (7.5  µg/kg per minute) for 75 minutes. A pulmonary artery catheter was used for measurements of systemic hemodynamics, and a renal vein catheter was used to measure renal plasma flow by the infusion clearance technique for PAH (para-aminohippurate) corrected by renal extraction of PAH . Filtration fraction was measured by renal extraction of chromium ethylenediamine tetraacetic acid. A total of 32 patients completed the study. Following treatment, the levosimendan and dobutamine groups displayed similar increases in renal blood flow (22% and 26%, respectively) with no significant differences between groups. Glomerular filtration rate increased by 22% in the levosimendan group but remained unchanged in the dobutamine group ( P=0.012). Filtration fraction was not affected by levosimendan but decreased by 17% with dobutamine ( P=0.045). Conclusions In patients with chronic heart failure and renal impairment, levosimendan increases glomerular filtration rate to a greater extent than dobutamine and thus may be the preferred inotropic agent for treating patients with the cardiorenal syndrome. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 02133105.

Effects of Cardiopulmonary Bypass on Renal Perfusion, Filtration, and Oxygenation in Patients Undergoing Cardiac Surgery.

BACKGROUND: Acute kidney injury is a common complication after cardiac surgery with cardiopulmonary bypass. The authors evaluated the effects of normothermic cardiopulmonary bypass on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen supply/demand relationship, i.e., renal oxygenation (primary outcome) in patients undergoing cardiac surgery. METHODS: Eighteen patients with a normal preoperative serum creatinine undergoing cardiac surgery procedures with normothermic cardiopulmonary bypass (2.5 l · min · m) were included after informed consent. Systemic and renal hemodynamic variables were measured by pulmonary artery and renal vein catheters before, during, and after cardiopulmonary bypass. Arterial and renal vein blood samples were taken for measurements of renal oxygen delivery and consumption. Renal oxygenation was estimated from the renal oxygen extraction. Urinary N-acetyl-ß-D-glucosaminidase was measured before, during, and after cardiopulmonary bypass. RESULTS: Cardiopulmonary bypass induced a renal vasoconstriction and redistribution of blood flow away from the kidneys, which in combination with hemodilution decreased renal oxygen delivery by 20%, while glomerular filtration rate and renal oxygen consumption were unchanged. Thus, renal oxygen extraction increased by 39 to 45%, indicating a renal oxygen supply/demand mismatch during cardiopulmonary bypass. After weaning from cardiopulmonary bypass, renal oxygenation was further impaired due to hemodilution and an increase in renal oxygen consumption, accompanied by a seven-fold increase in the urinary N-acetyl-ß-D-glucosaminidase/creatinine ratio. CONCLUSIONS: Cardiopulmonary bypass impairs renal oxygenation due to renal vasoconstriction and hemodilution during and after cardiopulmonary bypass, accompanied by increased release of a tubular injury marker.

Severe overdose of quetiapine treated successfully with extracorporeal life support.

BACKGROUND: Quetiapine is a second-generation antipsychotic drug, used mainly in the treatment of psychotic disorders. Overdose is associated with sedation, tachycardia and a prolonged QT-interval on the ECG. Cardiovascular symptoms are uncommon but in severe cases profound cardiovascular depression may occur. OBJECTIVES: To report a case where extracorporeal circulatory support (ECCS) was used successfully in severe quetiapine overdose. CASE REPORT: A 40-year-old woman was admitted to the emergency department (ED) with reduced consciousness apparently due to intoxication. She had a history of schizophrenia and was treated with 900 mg of quetiapine daily. In the ED, she presented with immeasurable low blood pressure, irregular bradycardia, hypothermia and a Glasgow Coma Scale (GCS) of 8. An immunoassay test for tricyclic antidepressive agents (TCA) was positive. Despite resuscitation with intravenous fluids, intensive vasopressor treatment and renal replacement therapy (CRRT) the patient's condition deteriorated. The patient was quickly moved to an intensive care unit where ECCS could be instituted. The patient subsequently recovered after 4 days in the ICU without any residual symptoms. Further laboratory analysis did not confirm the immunoassay finding. CONCLUSIONS: Severe poisoning with quetiapine may imitate tricyclic antidepressant poisoning, and drug screening methods may be falsely positive for TCA. In case of cardiovascular collapse due to quetiapine overdose, ECCS may be life saving.