Per Ederoth

Incidence, dynamics, and prognostic value of acute kidney injury for death after cardiac surgery.

OBJECTIVE This study relates long-term mortality after cardiac surgery to different methods of measuring postoperative renal function, classified according to the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. The dynamics of acute kidney injury during hospital stay were studied by comparing renal function preoperatively, at its poorest measurement, and at discharge. METHODS A total of 5746 patients undergoing coronary artery bypass grafting were studied in a Cox analysis, over a median follow-up time of 6.0 years (range, 2.5-9.5 years). Renal function was determined using the highest and discharge levels of plasma creatinine by Cockroft-Gault and Modification of Diet in Renal Disease formulae. Acute kidney injury was classified according to the RIFLE criteria. Renal recovery was studied in a 2-dimensional matrix, and the impact of renal function at different time points was related to survival. RESULTS Although the p-creatinine classified most patients in the nonacute kidney injury and Risk class; the Cockroft-Gault and Modification of Diet in Renal Disease formulae classified more patients in Injury and Failure classes; and higher Risk, Injury, and Failure classes were associated with increased long-term mortality. The effect of renal recovery on long-term survival was only in part associated with improved outcome. In addition, the poorest renal function was a stronger predictor of mortality compared with preoperative and discharge levels. CONCLUSIONS Classification using RIFLE criteria seems to be useful because it detects patients with renal impairment that affects long-term survival. The Modification of Diet in Renal Disease method seems to be the most robust method when predicting outcome, and the poorest renal function was the best predictor of outcome. Renal recovery was generally associated with better outcome.

Increased blood-brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysis.

Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood–brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half‐life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration–time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue.

Altered brain exposure of morphine in experimental meningitis studied with microdialysis

Background:  During pathologic conditions such as meningitis and traumatic brain injury the function of the blood–brain barrier (BBB) is disturbed. In the present study we examined the cerebral pharmacokinetic pattern of morphine in the intact brain and during experimentally induced meningitis using a pig model. Secondly, the use of intracerebral microdialysis as a potential tool for monitoring damage in the BBB by studying the pharmacokinetics of morphine is addressed.

The influence of age on the distribution of morphine and morphine-3-glucuronide across the blood–brain barrier in sheep

Background and purpose:  The effect of age on the distribution of morphine and morphine‐3‐glucuronide (M3G) across the blood–brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied.

Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care.

Background: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. Methods: The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 w l/min) with a Ringer solution from a microinfusion pump and analyzed for glucose, lactate, and glycerol. The study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. Results: The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The correlation was relatively poor for 1-6 h after insertion of the probes. During this period, a continuous increase in the subcutaneous level of glucose and decreases in lactate and glycerol were noted. Conclusions: The correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6 h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.

S100B Profiles and Cognitive Function at High Altitude

Exposure to high altitude can lead to acute mountain sickness (AMS) and high altitude cerebral edema (HACE). In this study we investigated the effect of high altitude on neurocognitive function and S100B release. Increased S100B release has been hypothesized to signify a loss of integrity in the blood-brain barrier (BBB). Seven healthy volunteers trekked to Capanna Regina Margherita (4554 m above sea level) in the Monte Rosa massif. During ascent and descent, five test events were undertaken; participants underwent neurocognitive testing, Lake Louise scoring (LLS), and blood sampling to measure levels of S100B. The blood tests revealed that S100B levels increased 42% to 122% from baseline, and mean LLS increased from 0.57 to 2.57. A significant correlation was observed between both S100B levels and LLS and S100B and some neurocognitive scores. The study indicates that S100B can be released by a mild hypoxia during AMS. Moreover, an observed correlation between S100B and a lower score on neurocognitive tests suggests that the pathogenetic mechanisms may be linked. The study indicates that a decline in cognitive function is associated with symptoms of AMS.

Erythropoietin and protection of renal function in cardiac surgery (the EPRICS Trial).

Background:To date, there are no known methods for preventing acute kidney injury after cardiac surgery. Increasing evidence suggests that erythropoietin has renal antiapoptotic and tissue protective effects. However, recent human studies have shown conflicting results. The authors aimed to study the effect of a single high-dose erythropoietin preoperatively on renal function after coronary artery bypass grafting in patients with preoperative impaired renal function. Methods:This single-center, randomized, double-blind, placebo-controlled study included 75 patients scheduled for coronary artery bypass grafting with preexisting renal impairment estimated glomerular filtration rate based on p-cystatin C (<60 and >15 ml/min). The patients either received a single high-dose erythropoietin (400 IU/kg) or placebo preoperatively. The primary endpoint was renal protection evaluated by p-cystatin C at the third postoperative day compared to the preoperative values. Incidence of acute kidney injury and other renal biomarker changes were among secondary endpoints. Results:There was no statistically significant difference on the third postoperative day for relative p-cystatin C level changes from baseline between the groups, 131 ± 31% (mean ± SD) for the study group and 125 ± 24% for the control group (P = 0.31; 95% CI, −0.6 to 20% for the difference). There were no statistically significant differences in other renal biomarkers or measures between the groups (p-neutrophil gelatinase–associated lipocalin, p-creatinine, p-urea, and estimated glomerular filtration rate). There were no other differences in outcome variables between the groups. Conclusion:Intravenous administration of a single high-dose (400 IU/kg) erythropoietin did not have a renal protective effect on patients with reduced kidney function undergoing coronary artery bypass surgery.

Blood transfusion after cardiac surgery: is it the patient or the transfusion that carries the risk?

Background: The transfusion of red blood cells (RBCs) after cardiac surgery has been associated with increased long‐term mortality. This study reexamines this hypothesis by including pre‐operative hemoglobin (Hb) levels and renal function in the analysis.

Evaluation of cystatin C with iohexol clearance in cardiac surgery.

Background: Post‐operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery.

Risks Associated With the Transfusion of Various Blood Products in Aortic Valve Replacement.

BACKGROUND Patients undergoing cardiac operations often require transfusions of red blood cells, plasma, and platelets. From a statistical point of view, there is a significant collinearity between the components, but they differ in indications for use and composition. This study explores the relationship between the transfusion of different blood components and long-term mortality in patients undergoing aortic valve replacement alone or combined with revascularization. METHODS A retrospective single-center study was performed including 1,311 patients undergoing aortic valve replacement. Patients who received more than 7 units of red blood cells, those who died early (7 days), and emergency cases were excluded. Patients were monitored for up to 9.5 years. A broad selection of potential risk factors were analyzed using Cox proportional hazards regression, where transfusion of red blood cells, plasma, and platelets were forced to remain in the model. RESULTS The transfusion of red blood cells was not associated with decreased long-term survival (hazard ratio [HR], 1.01; p = 0.520) nor was the transfusion of platelets (HR, 0.946; p = 0.124); however, the transfusion of plasma was (HR, 1.041; p < 0.001). All HRs are per unit of blood product transfused. No increased risk was found for patients undergoing a combined procedure. CONCLUSIONS No significant risk for long-term mortality was associated with transfusion of red blood cells during the study period. However, the transfusion of plasma was associated with increased mortality.