Effect of Cyclosporine on Cytokine Production in Elective Coronary Artery Bypass Grafting: A Sub-Analysis of the CiPRICS (Cyclosporine to Protect Renal Function in Cardiac Surgery) Study.

OBJECTIVES: The augmented inflammatory response to cardiac surgery is a recognized cause of postoperative acute kidney injury. The present study aimed to investigate the effects of preoperative cyclosporine treatment on cytokine production and delineate factors associated with postoperative kidney impairment. DESIGN: A randomized, double-blind, placebo-controlled, single-center study. SETTING: At a tertiary care, university hospital. PARTICIPANTS: Patients eligible for elective coronary artery bypass grafting surgery; 67 patients were enrolled. INTERVENTIONS: Patients were randomized to receive 2.5 mg/kg cyclosporine or placebo before surgery. Cytokine levels were measured after the induction of anesthesia and 4 hours after the end of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Tissue-aggressive (interleukin [IL]-1ß, macrophage inflammatory protein [MIP]-1ß, granulocyte colony-stimulating factor [G-CSF], IL-6, IL-8, IL-17, MCP-1), as well tissue-lenient (IL-4) cytokines, were significantly elevated in response to surgery. Changes in cytokine levels were not affected by cyclosporine pretreatment. CONCLUSIONS: Elective coronary artery bypass grafting surgery with cardiopulmonary bypass triggers cytokine activation. This activation was not impacted by preoperative cyclosporine treatment.

Sevoflurane provides better haemodynamic stability than propofol during right ventricular ischaemia-reperfusion.

OBJECTIVES: To assess whether sevoflurane provides better haemodynamic stability than propofol in acute right ventricular (RV) ischaemia-reperfusion. METHODS: Open-chest pigs (mean ± standard deviation, 68.8 ± 4.2 kg) anaesthetized with sevoflurane (n = 6) or propofol (n = 6) underwent 60 min of RV free wall ischaemia and 150 min of reperfusion. Haemodynamic parameters and blood flow in the 3 major coronary arteries were continuously monitored. Biomarkers of cardiac ischaemia were analysed. RESULTS: Mean arterial pressure and stroke volume decreased, whereas pulmonary vascular resistance increased equally in both groups. Heart rate increased 7.5% with propofol (P < 0.05) and 17% with sevoflurane (P < 0.05). At reperfusion, left atrial pressure and systemic vascular resistance decreased with sevoflurane. While RV stroke work (mmHg·ml) and cardiac output (l·min-1) decreased in the propofol group (4.2 ± 1.2 to 2.9 ± 1.7 and 2.65 ± 0.44 to 2.28 ± 0.56, respectively, P < 0.05 both), they recovered to baseline levels in the sevoflurane group (4.1 ± 1.5 to 4.0 ± 1.5 and 2.77 ± 0.6 to 2.6 ± 0.5, respectively, P > 0.05). Circumflex and left anterior descending coronary artery blood flow decreased in both groups. Right coronary artery blood flow (ml·min-1) decreased with propofol (38 ± 9 to 28 ± 9, P < 0.05), but not with sevoflurane (28 ± 11 to 28 ± 17, P > 0.05). Biomarkers of cardiac ischaemia increased in both groups. CONCLUSIONS: Compared to propofol, sevoflurane-anaesthetized pigs showed higher RV stroke work, cardiac output and right coronary artery blood flow during reperfusion. These findings warrant a clinical trial of sevoflurane in RV ischaemia in humans.

Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction.

OBJECTIVES: Primary graft dysfunction is a severe form of acute lung injury and a major cause of early morbidity and mortality encountered after lung transplant.We used a customized PExA 2.0 instrument (PExA, Gothenburg, Sweden) to measure particle flow in exhaled air during mechanical ventilation in the intensive care unit. Our objective was to discover whether patients who developed primary graft dysfunction had different particle flow patterns from the airways. We used volume-controlled ventilation and pressure-controlled ventilation to see whether changes in particle patterns could be observed in both mechanical ventilation settings. MATERIALS AND METHODS: First, we investigated whether it was safe to use a customized PExA 2.0 in conjunction with mechanical ventilation. Next, 12 lung transplant patients were randomized to either daily volumecontrolled ventilation or pressure-controlled ventilation as the first mode of treatment until extubation. RESULTS: In our study group, 6 patients did not develop primary graft dysfunction and 6 developed primary graft dysfunction. Patients with primary graft dysfunction underwent mechanical ventilation significantly longer; they also showed a stepwise increase in particle count from day 0 until extubation. We observed no adverse events related to the PExA 2.0 device. CONCLUSIONS: This study suggests that the PExA 2.0 device is safe to use in conjunction with mechanical ventilation in the intensive care unit. Lung transplant patients who developed primary graft dysfunction showed a different particle profile from the airways before clinical signs of primary graft dysfunction developed. Online assessment of ventilation impact before presentation of tissue changes may allow realtime detection of primary graft dysfunction, thus preventing or reducing its effects.

Different particle flow patterns from the airways after recruitment manoeuvres using volume-controlled or pressure-controlled ventilation.

OBJECTIVES: Noninvasive online monitoring of different particle flows from the airways may serve as an additional tool to assess mechanical ventilation. In the present study, we used a customised PExA, an optical particle counter for monitoring particle flow and size distribution in exhaled air, to analyse airway particle flow for three subsequent days. We compared volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) and performed recruitment manoeuvres (RM). METHODS: Six animals were randomised into two groups: half received VCV before PCV and the other half received PCV before VCV. Measurements were taken daily for 1 h in each mode during three subsequent days in six fully anaesthetised domestic pigs. A RM was performed twice daily for 60 s at positive end-expiratory pressure (PEEP) of 10, 4 breaths/min and inspiratory-expiratory ratio (I:E) of 2:1. Measurements were taken for 3 min before the RM, 1 min during the RM and for 3 min after the RM. The particle sizes measured were between 0.48 and 3.37 µm. RESULTS: A significant stepwise decrease was observed in total particle count from day 1 to day 3, and at the same time, an increase in fluid levels was seen. Comparing VCV to PCV, a significant increase in total particle count was observed on day 2, with the highest particle count occurring during VCV. A significant increase was observed comparing before and after RM on day 1 and 2 but not on day 3. One animal developed ARDS and showed a different particle pattern compared to the other animals. CONCLUSIONS: This study shows the safety and useability of the PExA technique used in conjunction with mechanical ventilation. We detected differences between the ventilation modes VCV and PCV in total particle count without any significant changes in ventilator pressure levels, FiO2 levels or the animals' vital parameters. The findings during RM indicate an opening of the small airways, but the effect is short lived. We have also showed that VCV and PCV may affect the lung physiology differently during recruitment manoeuvres. These findings might indicate that this technique may provide more refined information on the impact of mechanical ventilation.

ABO-identical matching has no superiority in long-term survival in comparison to ABO-compatible matching in lung transplantation.

BACKGROUND: Even though identical blood group matching between recipient and donor is preferred, it is still not clear by how much this improves the outcome for patients who received a lung transplant (LTx), or whether there is any survival benefit. Earlier studies have yielded ambiguous results and few have investigated long-term survival. The aim of this study is, therefore, to explore the different outcomes of identical and compatible recipient and donor blood group matching to determine whether identical matching is superior (LTx). METHOD: Between January 1990 to June 2016, 297 patients underwent primary LTx, 10 patients underwent heart and lung transplantation (HLTx), and 18 patients required re-transplantation (Re-LTx) at Skåne University Hospital in Lund. With a total of 325 transplantations at our center, 262 were ABO-identically matched while 53 were ABO-compatible. For survival analyses, the end-point used was retransplantation-free survival in addition to excluding HLTx (n = 10), assessed by Cox regression and Kaplan-Meier. RESULTS: ABO-compatible patients had a median of 49 days (2-641), and ABO-identical patients had a median of 89 days (1-1717) (p = 0.048) on the transplant waiting list. Patients with a limited survival up to 1-year showed significant difference in survival rate for ABO-compatible recipients compared to ABO-identical recipients (p < 0.05), however no significant difference was shown in overall survival between the two groups (p > 0.05), with the same pattern shown in patients with a limited survival rate up to ten years, emphysema-patients, when excluding single-LTx and patients transplanted before 2005 and after 2005, respectively (p > 0.05). CONCLUSION: Recipients who received ABO-compatible matched grafts showed a similar survival rate to recipients who received ABO-identical matched grafts in the present study. Cytolomegalovirus and Ebstein Barr Virus mismatch were also identified as risk factors particular among emphysema patients. Since ABO-identical transplantations and ABO-compatible transplantations showed similar results, the present selection-bias of preferring ABO-identical lungs could be adjusted to increase organ allocation. It might also be possible to shorten recipient waiting list time, as an identical match showed over 80% higher time on the waiting list than a compatible, non-identical match.

A new way of monitoring mechanical ventilation by measurement of particle flow from the airways using Pexa method in vivo and during ex vivo lung perfusion in DCD lung transplantation.

BACKGROUND: Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters. METHODS: Particle flow was monitored in vivo, post mortem, and in ex vivo lung perfusion (EVLP) in six porcines with the Pexa (particles in exhaled air) instrument. Volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) were used to compare small versus large tidal volumes. The surfactant lipids dipalmitoylphosphatidylcholine (DPPC) and phosphatidylcholine (PC) were quantified by mass spectrometry. RESULTS: In vivo the particle mass in VCV1 was significantly lower than in VCV2 (p = 0.0186), and the particle mass was significantly higher in PCV1 than in VCV1 (p = 0.0322). In EVLP, the particle mass in VCV1 was significantly higher than in PCV1 (p = 0.0371), and the particle mass was significantly higher in PCV2 than in PCV1 (p = 0.0127). DPPC was significantly higher in EVLP than in vivo. CONCLUSIONS: Here, we introduce a new method for measuring particle flow during mechanical ventilation and confirm that these particles can be collected and analyzed. VCV resulted in a lower particle flow in vivo but not in EVLP. In all settings, large tidal volumes resulted in increased particle flow. We found that DPPC was significantly increased comparing in vivo with EVLP. This technology may be useful for developing strategies to preserve the lung and has a high potential to detect biomarkers.

Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent Postoperative Decreases in Renal Function: A Randomized Clinical Trial.

BACKGROUND: Acute kidney injury is a common complication after cardiac surgery, leading to increased morbidity and mortality. One suggested cause for acute kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury. In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion injury in the kidneys. We hypothesized that administering cyclosporine before extracorporeal circulation could protect the kidneys in patients undergoing cardiac surgery. METHODS: The Cyclosporine to Protect Renal Function in Cardiac Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized, placebo-controlled, single-center study. The primary objective was to assess if cyclosporine could reduce acute kidney injury in patients undergoing coronary artery bypass grafting surgery with extracorporeal circulation. In the study, 154 patients with an estimated glomerular filtration rate of 15 to 90 ml · min · 1.73 m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine or placebo intravenously before surgery. The primary endpoint was relative plasma cystatin C changes from the preoperative day to postoperative day 3. Secondary endpoints included biomarkers of kidney, heart, and brain injury. RESULTS: All enrolled patients were analyzed. The cyclosporine group (136.4 ± 35.6%) showed a more pronounced increase from baseline plasma cystatin C to day 3 compared to placebo (115.9 ± 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001). The same pattern was observed for the other renal markers. The cyclosporine group had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk), I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in safety parameter distribution between groups. CONCLUSIONS: Administration of cyclosporine did not protect coronary artery bypass grafting patients from acute kidney injury. Instead, cyclosporine caused a decrease in renal function compared to placebo that resolved after 1 month.

Double lung, unlike single lung transplantation might provide a protective effect on mortality and bronchiolitis obliterans syndrome.

BACKGROUND: Survival after lung transplantation (LTx) is often limited by bronchiolitis obliterans syndrome (BOS). METHOD: Survey of 278 recipients who underwent LTx. The endpoint used was BOS (BOS grade ≥ 2), death or Re-lung transplantation (Re-LTx) assessed by competing risk regression analyses. RESULTS: The incidence of BOS grade ≥ 2 among double LTx (DLTx) recipients was 16 ± 3% at 5 years, 30 ± 4% at 10 years, and 37 ± 5% at 20 years, compared to single LTx (SLTx) recipients whose corresponding incidence of BOS grade ≥ 2 was 11 ± 3%, 20 ± 4%, and 24 ± 5% at 5, 10, and 20 years, respectively (p > 0. 05). The incidence of BOS grade ≥ 2 by major indications ranked in descending order: other, PF, CF, COPD, PH and AAT1 (p < 0. 05). The mortality rate by major indication ranked in descending order: COPD, PH, AAT1, PF, Other and CF (p < 0. 05). CONCLUSION: No differences were seen in the incidence of BOS grade ≥ 2 regarding type of transplant, however, DLTx recipients showed a better chance of survival despite developing BOS compared to SLTx recipients. The highest incidence of BOS was seen among CF, PF, COPD, PH, and AAT1 recipients in descending order, however, CF and PF recipients showed a better chance of survival despite developing BOS compared to COPD, PH, and AAT1 recipients.

Impact of Forced Expiratory Volume in 1 Second (FEV1) and 6-Minute Walking Distance at 3, 6, and 12 Months and Annually on Survival and Occurrence of Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation.

BACKGROUND Development of bronchiolitis obliterans syndrome (BOS) is a great limitation for patient survival in lung transplantation (LTx). A curative treatment for BOS is still missing, and in terminal stages re-transplantation (Re-LTx) is the only salvation. It is possible to slow the progress of BOS if it is detected at an early stage. This might be possible by assessing pulmonary function pattern. MATERIAL AND METHODS Between 1990 and 2014, 278 patients underwent LTx at Skåne University Hospital, Sweden. Pulmonary function was followed using spirometry (FEV1) and 6-minute walking test (6MWT) measured at 3, 6, and 12 months and annually. The endpoint used was freedom from BOS (BOS grade ≤1), BOS (BOS grade ≥2), and death or Re-LTx. RESULTS Double-lung transplantation (DLTx) showed a hazard ratio (HR) of 0.514 (p=0.001) versus recipients who underwent single-lung transplantation (SLTx). Regarding freedom from BOS, FEV1 showed an HR of 0.597 and 6MWT an HR of 0.982 (p<0.001). Regarding combined endpoint BOS ≥2 and Re-LTx, FEV1 showed an HR of 0.618 and 6MWT an HR of 0.972 (p<0.001). CONCLUSIONS Recipients with higher FEV1 or 6MWT values had better chances of survival. Recipients with DLTx had a significant survival benefit and a protective effect against development of BOS. As the distance that the patient can walk in 6 minutes increases, risk for death or Re-LTx is significantly lower, as is incidence of developing BOS grade ≥2. Understanding changes within pulmonary function are probably key to understanding patient prognosis.

Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS): a study protocol for a double-blind, randomised, placebo-controlled, proof-of-concept study.

INTRODUCTION: Acute kidney injury (AKI) after cardiac surgery is common and results in increased morbidity and mortality. One possible mechanism for AKI is ischaemia-reperfusion injury caused by the extracorporeal circulation (ECC), resulting in an opening of the mitochondrial permeability transition pore (mPTP) in the kidneys, which can lead to cell injury or cell death. Ciclosporin may block the opening of mPTP if administered before the ischaemia-reperfusion injury. We hypothesised that ciclosporin given before the start of ECC in cardiac surgery can decrease the degree of AKI. METHODS AND ANALYSIS: Ciclosporin to Protect Renal function In Cardiac Surgery (CiPRICS) study is an investigator-initiated double-blind, randomised, placebo-controlled, parallel design, single-centre study performed at a tertiary university hospital. The primary objective is to assess the safety and efficacy of ciclosporin to limit the degree of AKI in patients undergoing coronary artery bypass grafting surgery. We aim to evaluate 150 patients with a preoperative estimated glomerular filtration rate of 15-90 mL/min/1.73 m2. Study patients are randomised in a 1:1 ratio to receive study drug 2.5 mg/kg ciclosporin or placebo as an intravenous injection after anaesthesia induction but before start of surgery. The primary end point consists of relative P-cystatin C changes from the preoperative day to postoperative day 3. The primary variable will be tested using an analysis of covariance method. Secondary end points include evaluation of P-creatinine and biomarkers of kidney, heart and brain injury. ETHICS AND DISSEMINATION: The trial is conducted in compliance with the current version of the Declaration of Helsinki and the International Council for Harmonisation (ICH) Good Clinical Practice guidelines E6 (R1) and was approved by the Regional Ethical Review Board, Lund and the Swedish Medical Products Agency (MPA). Written and oral informed consent is obtained before enrolment into the study. TRIAL REGISTRATION NUMBER: NCT02397213; Pre-results.

25-year follow-up after lung transplantation at Lund University Hospital in Sweden: superior results obtained for patients with cystic fibrosis.

OBJECTIVES: In Sweden, two centres perform lung transplantation for a population of about 9 million and the entire population is covered for lung transplantation by government health insurance. Lund University Hospital is one of these centres. This retrospective report reviews the 25-year experience of the Skåne University Hospital Lung Transplant Program with particular emphasis on short-term outcome and long-term survival but also between different subgroups of patients and types of transplant [single-lung transplantation (SLTx) versus double-lung transplantation (DLTx)] procedure performed. METHODS: Between January 1990 and June 2014, 278 patients underwent lung transplantation at the Skåne University Hospital Sweden. DLTx was performed in 172 patients, SLTx was performed in 97 patients and heart-lung transplantation was performed in 9 patients. In addition, 15 patients required retransplantation (7 DLTx and 8 SLTx). RESULTS: Overall 1-, 5-, 10-, 15- and 20-year survival rates were 88, 65, 49, 37 and 19% for the whole cohort. DLTx recipients showed 1-, 5-, 10- and 20-year survival rates of 90, 71, 60 and 30%, compared with SLTx recipients with 1-, 5-, 10- and 20-year survival rates of 83, 57, 34 and 6% (P < 0.05), respectively. Comparing the use of intraoperative extracorporeal membrane oxygenation, extracorporeal circulation (ECC) and no circulatory support in the aspect of survival, a significant difference in favour of intraoperative ECC was seen. CONCLUSIONS: Superior long-term survival rates were seen in recipients diagnosed with cystic fibrosis, α1-antitrypsin deficiency and pulmonary hypertension. DLTx showed better results compared with SLTx especially at 10 years post-transplant. In the present study, we present cumulative incidence rates of bronchiolitis obliterans syndrome of 15% at 5 years, 26% at 10 years and 32% at 20 years post-transplant; these figures are in line with the lowest rates presented internationally.

The predictive value of s-cystatin C for mortality after coronary artery bypass surgery.

OBJECTIVES: To evaluate serum creatinine (s-creatinine) and serum cystatin C (s-cystatin C) levels and estimated glomerular filtration rate (eGFR) at different time points as predictors for mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 1638 patients undergoing elective CABG were studied prospectively over a median follow-up of 3.5 years (range, 2.0-5.0 years). Renal function was assessed by a comparison of s-creatinine, s-cystatin C values measured preoperatively and at the lowest postoperative level of renal function. The eGFR was estimated by different formulas: Modification of Diet in Renal Disease, the 2009 Chronic Kidney Disease Epidemiology (CDK-EPI) for s-creatinine, the 2012 CKD-EPI formula for s-cystatin C, the 2012 CKD-EPI formula for s-cystatin C and s-creatinine in combination, and the Caucasian Asian, Pediatric, and Adult subjects formula for s-cystatin C. Cox proportional hazards model analysis and C-statistics were used to evaluate independent predictors of mortality and to assess the predictive ability of the different renal function measures. RESULTS: The 30-day mortality was 0.8%. Overall survival was 96.1% ± 0.4% at 2 years and 90.0% ± 1.2% at 5 years. Preoperative s-cystatin C showed greater predictive power than s-creatinine for overall mortality (area under the curve, 0.794 vs 0.653). Preoperative s-cystatin C (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.36-1.99) and eGFR based on s-cystatin C (HR, 0.96; 95% CI, 0.95-0.98), were both independent predictors of mortality. The unadjusted HR for mortality comparing the lowest preoperative cystatin C quintile (Q1) with Q4-Q5 were as follows: Q1 versus Q5, HR, 2.0; 95% CI, 1.6-2.5 (P < .001); Q1 versus Q4, HR, 1.6; 95% CI, 1.2-2.2 (P = .005). CONCLUSIONS: The s-cystatin C level and s-cystatin C-based eGFR measured preoperatively are strong predictors for mortality after elective CABG.

Sevoflurane anesthesia during acute right ventricular ischemia in pigs preserves cardiac function better than propofol anesthesia.

BACKGROUND: The intention of the present study was to evaluate possible cardioprotective properties of inhalation anesthesia with sevoflurane. METHODS AND MATERIALS: A porcine, open-chest model of right ventricular ischemia was used in 7 pigs receiving inhalation anesthesia with sevoflurane. The model was earlier developed and published by our group, using pigs receiving intravenous anesthesia with propofol. They served as controls. The animals were observed for three hours after the induction of right ventricular ischemia by ligation of the main branches supplying the right ventricular free wall. RESULTS: In the sevoflurane group, the cardiac output recovered 2 hours after the induction of ischemia and intact right ventricular stroke work was observed. In the propofol group, no such recovery occurred. The release of troponin T was significantly lower than in the sevoflurane group. CONCLUSIONS: Inhalation anesthesia with sevoflurane seems superior to intravenous anesthesia with propofol in acute right ventricular ischemic dysfunction.

Transfusion of sex-mismatched and non-leukocyte-depleted red blood cells in cardiac surgery increases mortality.

OBJECTIVE: To examine the mortality risk of blood transfusions when donor information, postdonation treatment, and a wide selection of risk factors are taken into account. METHODS: A retrospective study was performed on 9907 patients who underwent coronary artery bypass grafting and/or aortic valve replacement. Several transfusion-related risk factors, including age of blood products, sex of donor, ABO group, Rh group, posttransfusion treatment, and sex matching, were included in the analysis. A wide selection of preoperative comorbidities were included as well. A Cox proportional hazards analysis was performed to determine significant risk factors. Patients were followed for a period of up to 12 years posttransfusion. RESULTS: We found an excess mortality for transfusions of sex-mismatched red blood cells (RBCs) per unit transfused (hazard ratio [HR], 1.083; 95% confidence interval [CI] 1.028-1.140; P = .003). In addition, we found a significant risk during the first year for transfusing 1 to 2 units of non-leukocyte-depleted RBCs (HR, 1.426; 95% CI, 1.004-2.024; P = .047). Transfusion of 1 to 2 units of leukocyte-depleted RBCs was not associated with increased risk (HR, 0.981; 95% CI, 0.866-1.110; P = not significant). The age of blood products was not associated with increased mortality. CONCLUSIONS: In this large retrospective study, transfusion of non-sex-matched RBCs was associated with increased mortality. In addition, in patients receiving small amounts of blood, leukocyte depletion of RBCs had a beneficial effect on patient survival.

Outcome of inotropic therapy: is less always more?

PURPOSE OF REVIEW: Positive inotropic agents are widely used in the management of the critical ill patient presenting with low cardiac output state. Different inotropic agents are available, and different effects on hemodynamic endpoints may be recognized, but data on relevant clinical endpoints are scarce. A growing body of literature suggests that overuse of inotropes may have detrimental effects on cardiomyocytes, resulting in an increased risk of morbidity and mortality. The present review will summarize recent literature, focusing on outcome studies among adult patients related to use of inotropes in different clinical settings. RECENT FINDINGS: Use of inotropic therapy shows a manifold variation between hospitals and individual providers even after risk standardization. No recent studies have shown inotropic therapy to provide short-term and long-term improvement of morbidity and mortality in patients with advanced nonsurgical heart failure or septic shock or as part of goal-directed treatment in high-risk noncardiac surgery. Levosimendan may show beneficial effect on mortality in cardiac surgery. CONCLUSION: A 'less is more' approach may show to be appropriate when relating to routine use of inotropes. Inotropic therapy should be restricted to patients with heart failure and clinical signs of end-organ hypoperfusion.

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.

Preoperative pulmonary hypertension and its impact on survival after heart transplantation.

OBJECTIVES: Pulmonary hypertension (PH) due to left heart disease may impair outcome after heart transplantation (HT). To evaluate to what extent previous, and present, haemodynamic criteria discriminate the impact of pre-operative-PH on survival, we characterized the PH in our HT-patients according to ESC's guidelines, ISHLT's summary statement and ISHLT's relative contraindications and criteria for early risk of death after HT. DESIGN: Records from the 215 HT-patients in Lund during 1988-2010 were reviewed. Subsequent analysis included adults (n = 94) evaluated with right-heart-catheterization at our lab, at rest before HT. End of follow-up was 30th of June 2012. RESULTS: Survival (mean, n) did not differ (p = ns) for the 94 HT-patients; without (13.0 years, n = 28) or with (13.9 years, n = 66) PH, passive (13.8 years, n = 50) or reactive (12.2 years, n = 13) post-capillary-PH, "modified" passive (13.1 years, n = 40), mixed (16.6 years, n = 23), "modified" reactive (12.6 years, n = 7) or non-reactive (12.2 years, n = 8) post-capillary-PH; or for ISHLT's relative contraindications (12.0 years, n = 22) or increased risk of right-heart-failure and early death (16.5 years, n = 23) after HT. CONCLUSIONS: As previous and present haemodynamic criteria did not sufficiently discriminate the impact of pre-operative-PH for survival after HT at our centre, larger multi-centre studies are encouraged to redefine criteria that may influence outcome.

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.

A porcine model for acute ischaemic right ventricular dysfunction.

OBJECTIVES: To establish an experimental model for acute ischaemic isolated right ventricular dysfunction and the subsequent haemodynamic changes. METHODS: An open-chest porcine model with ischaemic dysfunction of the right ventricle induced by ligation of the three main branches supporting the right ventricular free wall. Invasive monitoring of mean arterial blood pressure (MAP), central venous pressure (CVP), left atrial pressure (LAP) and right ventricular pressure (RVP); ultrasonic measurement of cardiac output (CO) and calculation of haemodynamic parameters such as stroke volume (SV), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) using standard formulae. RESULTS: The ischaemic challenge to the right ventricle resulted in a significant (≥30%) reduction in RVSW associated with an increase (6-25%) in CVP and reduction (8-18%) in pulmonary artery pressure (PAP) despite unchanged PVR, all reflecting the failing right ventricle. There was also a significant drop in CO (14-22%) despite unchanged LAP indicating lessened transpulmonary delivery of left ventricular preload due to the failing right ventricle causing the haemodynamic compromise rather than left ventricular failure. Supraventricular and ventricular arrhythmias occurred in three and two out of seven pigs, respectively-all of which except one were successfully resuscitated with cardioversion and/or defibrillation. CONCLUSIONS: This novel open-chest porcine model of induced ischaemia of the right ventricular free wall resulted in significant haemodynamic compromise confirmed using standard haemodynamic measurements making it useful for further research on acute, ischaemic isolated right ventricular failure.