Sven‐Erik Ricksten

This study evaluates mannitol as a clearance marker for measuring glomerular filtration rate (GFR) in outpatients with chronic kidney disease (CKD). Multi‐sample iohexol clearance served as the reference method. Twenty patients with CKD, stages 3–4, received bolus injections of both clearance markers simultaneously. Blood samples were collected 3, 5 and 22 h after the bolus injections. Marker concentrations were analyzed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). A calculation template, based on the Bröchner–Mortensen multi‐sample model, was applied to determine GFR for both markers. In addition, plasma clearance of mannitol was assessed using the one‐sample Jacobsson equation, applied to samples taken 5 and 22 h after the bolus injection of mannitol. Agreement between the clearance methods was assessed by the Bland‐Altman method, and the accuracy of mannitol clearance versus iohexol clearance was assessed by calculating P30 and P10. For the multi‐sample clearance, the between‐methods bias was 0.95 ± 1.4 mL/min/1.73 m², the error was 10%, and the accuracy was 100% for both P30 and P10. The corresponding values for bias, error, P30 and P10 for the one‐sample plasma clearance of mannitol versus the reference method were: −2.3 ± 3.6 and 2.9 ± 3.0 mL/min/1.73 m², 24% and 21%, 95% and 100%, 80% and 60%, respectively for samples obtained 5 and 22 h after the bolus. Mannitol exhibited a reliable performance as a clearance marker in patients with CKD, stages 3–4, and may serve as an alternative when standard markers, iohexol or isotopes, are contraindicated. However, further large‐scale studies are required to confirm these findings.

Background: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with impaired renal oxygenation and acute kidney injury. The authors investigated whether an amount higher than their standard blood flow during CPB could improve renal blood flow, the oxygen demand–supply relationship, and function and attenuate tubular injury. Methods: After ethical approval and informed consent, 36 adult patients undergoing cardiac surgery received either high flow (2.9 l · min^–1 · m^–2, n = 19) or standard flow (2.4 l · min^–1 · m^–2, n = 17) during CPB in this randomized, nonblinded, parallell-arm study. Systemic hemodynamics and renal variables were measured before and during CPB. Glomerular filtration rate was measured by infusion clearance of iohexol and renal blood flow by infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid, using a renal vein catheter. Renal oxygen demand–supply relationship was estimated from renal oxygen extraction and tubular injury assessed by urinary N-acetyl-β-d-glucosaminidase. Results: During CPB, high flow led to a larger increase in systemic oxygen delivery (100 [95% CI, 60 to 141] vs. 31 [1.9 to 65] ml · min^–1 · m^–2]; between-group P < 0.001; effect size Cohen’s dz, 0.59) and target mean arterial pressure was maintained at a lower norepinephrine dose (0.03 [–0.01 to 0.06] µg · kg^–1 · min^–1] vs. 0.10 [0.02 to 0.19] µg · kg^–1 · min^–1; P = 0.048; Cohen’s dz, 0.62) compared with standard flow. There were no differences in renal blood flow or oxygen extraction between groups. Glomerular filtration rate increased during high-flow CPB (6.4 [1.9 to 10.9] ml · min^–1 · 1.73 m^–2), but not in the standard-flow group (–2.3 [–10.9 to 6.2] ml · min^–1 · 1.73 m^–2; between-group P = 0.044; Cohen’s dz, 0.66). The peak urinary excretion of N-acetyl-β-d-glucosaminidase was 1.42 (0.87 to 3.6) versus 3.74 (1.5 to 7.7) units/µmol creatinine in the high-flow and standard-flow groups, respectively (P = 0.049). No perfusion-related adverse events were seen in either group. Conclusions: A 20% higher-than-standard CPB flow during cardiac surgery improved renal function, whereas no change in renal blood flow or oxygen demand–supply relationship could be detected. Higher CPB flow was associated with a less pronounced tubular injury marker release compared with standard flow.

Background: Haemorrhage is a leading cause of morbidity and mortality in trauma, and prehospital transfusion of blood products is often necessary. Whole blood has been proposed to be the best alternative, but it is unclear whether, and how, storage and transport of the blood in a helicopter affects the blood units. We investigated the coagulation capacity and platelet function in whole blood at different time points during helicopter missions.Methods: Twenty units of low‐titre group O RhD negative whole blood were collected from healthy volunteers and analysed before, during and after transport in a helicopter. Coagulation and platelet function, as measured by thromboelastography, and blood samples for pH, electrolytes, glucose and lactate were assessed at baseline and 24, 72 and 168 h after storage in the helicopter. Plasma concentrations of coagulation factors and haemoglobin and blood counts were measured at baseline and after 168 h.Results: Plasma concentrations of coagulation factors and haemoglobin did not change during storage and transport. Platelet counts decreased from a baseline mean of 172 ± 29 × 10⁹/L to a mean of 120 ± 28 × 10⁹/L after 168 h, and platelet function worsened slightly but significantly by 8%–9% during storage and transport. pH and glucose decreased while potassium and lactate levels increased after 168 h compared with baseline.Conclusion: Storage and transport of whole‐blood units in a rescue helicopter, for up to 168 h, had a slight impact on the blood quality. Storage of whole blood on board of the helicopter holds up to European standard, measured as temperature and haemolysis.

Background: Estimating equations for the assessment of glomerular filtration rate (GFR) have been poorly investigated in the critical care setting. We evaluated the agreement between the GFR measured with ⁵¹CrEDTA/iohexol (mGFR) and four estimating equations based on serum concentrations of creatine and/or cystatin C (eGFR) in two cohorts: critically ill patients and outpatients with normal‐to‐moderately reduced GFR.Methods: Forty‐three patients in the critical care group and 48 patients in the outpatient group were included. GFR was measured (mGFR) by plasma infusion clearance of ⁵¹Cr‐EDTA/iohexol (critical care group) and the single injection, one‐sample plasma ⁵¹Cr‐EDTA clearance technique (outpatients). The following estimating equations (eGFR) were used: the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation for creatinine (CKD‐EPI_Cr), cystatin C (CKD‐EPI_{Cys C}), creatinine+cystatin C (CKD‐EPI_{Cr + Cys C}) and the Lund‐Malmö creatinine+cystatin C equation (LM_{Cr + Cys C}). Agreement between mGFR and eGFR was assessed by the Bland–Altman method and accuracy by calculating P30 and P10.Results: In the critically ill group, the bias between the estimating equations and mGFR was −3.6 to 2.8 mL/min/1.73 m², while the error was 121%–127% and the accuracy (P30) 33%–40%. In the outpatients, the bias between the estimating equations and mGFR was −13.0 to 7.6 mL/min/1.73 m², while the error was 31%–41% and the accuracy (P30), 67%–96%.Conclusions: All four equations performed poorly in assessing GFR in the critically ill cohort with an unacceptably high error and low accuracy in contrast to the outpatient group. To accurately assess GFR in critically ill patients, GFR must be measured not estimated.Editorial Comment: For the assessment of glomerular filtration rate (GFR), it can be measured directly, but is frequently estimated using a point measure of serum creatinine concentration. In this study, ICU case GFR estimations, by different adjusted equations, done also for a cohort of outpatients, showed that these serum creatinine‐based estimations for ICU cases are not highly precise or reliable.

The hemodynamic definitions of pulmonary hypertension consider resistive loading (pulmonary vascular resistance [PVR]), but there are increasing evidence that pulsatile loading (pulmonary artery compliance [PAC]) has functional and prognostic importance. The aims of the present study on patients with left heart disease, were to evaluate a novel echocardiographic right ventricular (RV) afterload score and to investigate its relation to risk of mortality or implantation of a left ventricular assist device. Patients (n = 220) with left ventricular ejection fraction < 50% consecutively referred for heart transplant or heart failure workup underwent echocardiography and right heart catheterization. Four metrics were included in the afterload score: the systolic pulmonary artery pressure (sPAP_Doppler) and three variables related to pressure reflection in the pulmonary circulation. Two points were allocated for sPAP_Doppler ≥ 60 mmHg and for each pressure reflection variable indicating PVR > 3 Wood units (WU). One point was allocated for sPAP_Doppler 36–59 mmHg and for pressure reflection variables above the upper normal limit. Low afterload was defined as 0‐to‐1 points, intermediate as 2‐to‐4 points, and high as 5‐to‐8 points. There were in‐between the groups significant differences in PAC and PVR. A 5‐point RV dysfunction score showed with stepwise increased RV afterload more severe dysfunction. Unadjusted hazard ratio for endpoint was 3.34 (1.69–6.79) for intermediate score, and 5.11 (2.52–10.40) for patients with high score. In conclusion, in patients with severe heart failure, a novel echocardiographic RV afterload score is related to increased pulsatile and resistant load, more severe RV dysfunction, and increased risk of adverse outcome.

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.

BackgroundRenal 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.MethodsA 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.ResultsThe 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%.ConclusionseGFR 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.

Background: Systemic haemodynamic effects of intrathecal anaesthesia in an aging and frail population has not been well investigated. We examined the systemic haemodynamics of fractional spinal anaesthesia following intermittent microdosing of a local anaesthetic and an opioid. Methods: We included 15 patients aged over 65 with significant comorbidities, planned for hip fracture repair. Patients received a spinal catheter and cardiac output monitoring using the LiDCOplus system. All measurements were performed prior to start of surgery. Invasive mean arterial pressure (MAP), cardiac index (CI), systemic vascular resistance index (SVRI), heart rate and stroke volume index (SVI) were registered. Two doses of bupivacaine 2.25 mg and fentanyl 15 µg were administered with 25-minute intervals. Hypotension was defined as a fall in MAP by >30% or a MAP <65 mmHg. Results: The incidence of hypotension was 30%. Hypotensive patients (n=5) were treated with low doses of norepinephrine (0.01-0.12 µg/kg/min). MAP showed a maximum reduction of 17% at 10 minutes following the first dose. CI, systemic vascular resistance index and stroke volume index decreased by 10%, 6%, and 7%, respectively, while heart rate was unchanged over time. After the second dose, none of the systemic haemodynamic variables were affected. Conclusions: Fractional spinal anaesthesia administered prior to surgery induced a minor to moderate fall in MAP, mainly caused by a reduction in cardiac output, induced by systemic venodilation, causing a fall in venous return. Our results are contrary to the widely held belief that hypotension is mainly the result of a reduction of systemic vascular resistance.

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.

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 β‐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 β‐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.