https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)04211-2.pdf

Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study

It has been known for 50 years that transaminase activity increases in patients with acute myocardial infarction. With the development of creatine kinase (CK), biomarkers of cardiac injury began to take a major role in the diagnosis and management of patients with acute cardiovascular disease. In 2000 the European Society of Cardiology and the American College of Cardiology recognized the pivotal role of biomarkers and made elevations in their levels the “cornerstone” of diagnosis of acute myocardial infarction. At that time, they also acknowledged that cardiac troponin I and T had supplanted CK-MB as the analytes of choice for diagnosis. In this review, we discuss the science underlying the use of troponin biomarkers, how to interpret troponin values properly and how to apply these measurements to patients who present with possible cardiovascular disease.

https://www.cmaj.ca/content/cmaj/173/10/1191.full.pdf

Troponin: the biomarker of choice for the detection of cardiac injury

Background
Hydroxyethyl starches (HES) are synthetic colloids commonly used for fluid resuscitation to replace intravascular volume, yet they have been increasingly associated with adverse effects on kidney function. This is an update of a Cochrane review first published in 2010.

Objectives
To examine the effects of HES on kidney function compared to other fluid resuscitation therapies in different patient populations.

Search methods
We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference lists of articles. The most recent search was completed on November 19, 2012.

Selection criteria
Randomised controlled trials (RCTs) and quasi-RCTs in which HES was compared to an alternate fluid therapy for the prevention or treatment of effective intravascular volume depletion. Primary outcomes were renal replacement therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as defined by the RIFLE criteria.

Data collection and analysis
Screening, selection, data extraction and quality assessments for each retrieved article were carried out by two authors using standardised forms. All outcomes were analysed using relative risk (RR) and 95% confidence intervals (95% CI). Authors were contacted when published data were incomplete. Preplanned sensitivity and subgroup analyses were performed after data were analysed with a random-effects model.

Main results
This review included 42 studies (11,399 patients) including 19 studies from the original review (2010), as well as 23 new studies. Fifteen studies were excluded from the original review (nine retracted from publication due to concerns about integrity of data and six lacking individual patient creatinine data for the calculation of RIFLE criteria). Overall, there was a significant increase in the need for RRT in the HES treated individuals compared to individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49; 19 studies, 9857 patients) and the number with author-defined kidney failure (RR 1.59, 95% CI 1.26 to 2.00; 15 studies, 1361 patients). The RR of AKI based on RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, 8402 participants). The risk of meeting urine output and creatinine based RIFLE-R (risk) criteria for AKI was in contrast in favour of HES therapies (RR 0.95, 95% CI 0.91 to 0.99; 20 studies, 8769 patients). However, when RIFLE-R urine output based outcomes were excluded as per study protocol, the direction of AKI risk again favoured the other fluid type, with a non-significant RR of AKI in HES treated patients (RR 1.05, 95% CI 0.97 to 1.14; 8445 patients). A more robust effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95% CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high molecular weight (MW) and degree of substitution (DS) versus low MW and DS (≥ 200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low dose treatments (i.e. ≥ 2 L versus < 2 L). There were differences identified between sepsis versus non-sepsis subgroups for the RIFLE-R and RIFLE-I based outcomes only, which may reflect the differing renal response to fluid resuscitation in pre-renal versus sepsis-associated AKI. Overall, methodological quality of the studies was good.

Authors' conclusions
The current evidence suggests that all HES products increase the risk in AKI and RRT in all patient populations and a safe volume of any HES solution has yet to be determined. In most clinical situations it is likely that these risks outweigh any benefits, and alternate volume replacement therapies should be used in place of HES products.

Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function

Rapid quantification of malondialdehyde in plasma by high performance liquid chromatography-visible detection.

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

/pdf/management-of-the-potential-organ-donor-in-the-icu-society-17ltdvdbv2.pdf

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement

BACKGROUND The effect of hydroxyethyl starch (HES) on early allograft function was examined retrospectively in a cohort of 119 renal transplantations realized by local organ exchange between four cooperating centres. METHODS After exclusions, 109 transplant procedures were subdivided in three groups according to donor colloid loading: (i) HS-group (Haes steril 6%, mean volume (SD): 979 (946) ml, n = 20); (ii) PS-group [Plasmasteril, mean volume (SD): 769 (411) ml, n = 16]; and (iii) control group (gelatin albumin, n=73). RESULTS Delayed graft function (DGF), defined as the need for dialysis during the first post-transplant week, occurred in 3/20 (15%) cases in the HS-group, in 5/16 (31%) cases in the PS-group and in 14/73 (19%) cases in the control group (P = 0.450). Uni- and multivariate analysis revealed older donor age (P = 0.001) and kidney preservation with histidine-tryptophan-ketoglutarate (HTK) (P = 0.001) as the only factors associated with a higher incidence of DGF. CONCLUSIONS Renal function as measured by daily serum creatinine concentration and 24 h urinary output up to 14 days post-transplantation in the HS-group was comparable with that of controls. The higher serum creatinine observed during the first seven post-transplant days in the PS-group could be related to higher donor age and haemodynamic instability, and recipient male preponderance, rather than to HES itself.

Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis.

Background. In patients with end-stage renal disease (ESRD), treated with haemodialysis, a high overall mortality is observed. A previous study showed that cardiac troponin T (cTnT) is a strong independent predictor of outcome in this population. In this study we investigated possible causes of cTnT increase and its relationship with a marker of oxidative stress. Methods. In a group of 71 haemodialysis patients (36 male, 35 female, mean age 68.7 ± 1.5 years) we determined cTnT and compared its presence with several biochemical parameters and with malondialdehyde (MDA), which is an indicator of oxidative stress. None of the patients suffered an acute coronary event during the observation period. Three measurements of cTnT and MDA were performed with a 2-week interval. Forty-nine patients underwent a transthoracic echocardiography. Results. Twenty-nine patients (or 40.8%) had a positive cTnT determination (defined as cTnT ≥ 0.10 ng/ml). cTnT positive patients had significantly higher levels of MDA (P=0.0125), C-reactive protein (CRP) (P=0.04) and pre-dialysis urea (P=0.04). Regression analysis showed that both pre-dialysis urea and MDA independently influenced cTnT. No correlation was found with age, dialysis adequacy, post-dialysis urea, total cholesterol, white blood cell count, fibrinogen or any of the echocardiographical parameters. Presence of heart failure, diabetes or use of medication could not discriminate between cTnT positive and cTnT negative patients. MDA levels correlated positively with time on haemodialysis (P=0.0021). Echocardiography showed left ventricular hypertrophy in 88% of the examined patients and impaired wall motion in 35%. Patients with clinical signs of heart failure had a lower ejection fraction and worse wall motion score index. No correlation existed between echocardiographic findings and cTnT or MDA. Survival was independently predicted by cTnT (P=0.0025), MDA (P= 0.0007), CRP (P=0.006) and age (P=(1.0143). Patients with both cTnT and CRP increase had a survival of < 50% at 1 year, compared with 90% in patients with both cTnT and CRP within the normal range and 80% when either CRP or cTnT was increased (X 2 = 12.127; P= 0.0023). Conclusions. This study confirms that the presence of cTnT predicts prognosis in ESRD. The presence of cTnT is linked to oxidative stress, inflammation and uraemia. The absence of specific findings on EKG and echocardiography points towards subclinical myocardial damage caused by endothelial disturbances.

/pdf/cardiac-troponin-t-and-malondialdehyde-modified-plasma-2tlmuqzsjf.pdf

Cardiac troponin T and malondialdehyde modified plasma lipids in haemodialysis patients

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Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis.

Cardiac troponin T and malondialdehyde modified plasma lipids in haemodialysis patients