Use of SAMe-TT2R2 in a racially diverse anticoagulation clinic: prediction of optimal anticoagulation.

The SAMe-TT2R2 score predicts optimal long-term oral Vitamin K Antagonist (VKA) anticoagulation for homogenous Caucasian and homogenous Asian populations for non-valvular atrial fibrillation but at different score thresholds. The score that predicts optimal VKA anticoagulation in significantly diverse populations for multiple indications for systemic anticoagulation has not been reported. We determined whether optimal VKA anticoagulation is predicted by SAMe-TT2R2 score in a diverse inner-city population for non-valvular atrial fibrillation (NVAF), unprovoked venous and pulmonary thromboembolic disease (VTE), mechanical prosthetic heart valves and all other indications. All patients on long term VKA's that attended an inner-city anticoagulation clinic between February 2016 and October 2017 were included in this study. Eligible patients were grouped according to oral anticoagulation indication: (1) NVAF, (2) VTE, (3) prosthetic valves and (4) other indications. Each patient's SAMe-TT2R2 score and percent time of INR in the therapeutic range (TTR) was calculated with optimal international normalized ratio (INR) control defined as TTR ≥ 65%. The correlation between SAMe-TT2R2 score and TTR was determined by logistic regression for each oral anticoagulant indication. Receiver operating characteristic curves were then used to identify the best cutoff for prediction of ≥ 65% TTR. Of 316 patients meeting study criteria, 54% were non-Caucasian and there was a significant negative correlation between the SAMe-TT2R2 score and TTR (coefficient - 0.35, P < 0.0001) for all patients. A SAMe-TT2R2 score < 4 was identified as the best threshold for predicting optimal TTR (Youden's J-statistics = 0.238) with accuracy and positive likelihood ratio of 63.4% and 1.73, respectively. The SAMe-TT2R2 score predicts optimal VKA anticoagulation for systemic anticoagulation for multiple indications in a diverse urban population at a higher score than the original report for non-valvular atrial fibrillation of a cohort where < 10% non-Caucasians.

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial.

BACKGROUND: Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing. OBJECTIVES: In this post hoc analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-Chronic Kidney Disease), we compared outcomes of patients not listed versus those listed according to management strategy. METHODS: In the ISCHEMIA-CKD trial (n = 777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction) and secondary (death, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed. RESULTS: Compared with those not listed, listed patients were younger (60 years vs 65 years), were less likely to be of Asian race (15% vs 29%), were more likely to be on dialysis (83% vs 44%), had fewer anginal symptoms, and were more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios for the primary outcome were 0.91 (95% confidence interval [CI]: 0.54-1.54) and 1.03 (95% CI: 0.78-1.37) for those listed and not listed, respectively (pinteraction= 0.68). Adjusted hazard ratios for secondary outcomes were 0.89 (95% CI: 0.55-1.46) in listed and 1.17 (95% CI: 0.89-1.53) in those not listed (pinteraction = 0.35). CONCLUSIONS: In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant. (ISCHEMIA-Chronic Kidney Disease Trial [ISCHEMIA-CKD]; NCT01985360).

Nationwide temporal variability of droughts in the Kingdom of Eswatini: 1981-2018.

For adequate mitigation and adaptation measures, it is essential to have detailed analysis of droughts patterns. This study determined the i) occurrence and severity of droughts ii) drought recurrence frequencies and iii) drought trends across different agro-ecological zones in the Kingdom of Eswatini for the period 1981 to 2018. A Standardised Precipitation Index (SPI) computed from long-term precipitation data measured from six meteorological stations was used to determine drought occurrence and severity. Python software (Version 3.6) was applied on the SPI values to predict the recurrence of drought events over time in years. The SPI showed that in the Highveld, 42% of the droughts were moderate, 32% were severe and the remaining 26%, which all occurred post 1980 were extreme (SPI -2.34 to -2.82). The Middleveld had an even proportion of drought categories (29-35%). The Lowveld recorded 62% of moderate, 8% severe and 30% extreme droughts of which 70% occurred post 2000. Moderate droughts were found to recur every 4-5 years while extreme droughts are expected every 13-21 years. These findings are essential for mitigation and adaptation measures geared towards the adverse effects of droughts.

Pylephlebitis presenting as spontaneous coronary sinus thrombosis: a case report.

BACKGROUND: Coronary sinus thrombosis is a rare phenomenon. When identified, it most often is a complication of infective endocarditis or procedural intervention. We present an unusual and unreported case of spontaneous coronary sinus thrombosis as embolic sequela of an intra-abdominal infectious process. CASE PRESENTATION: We report a case of a 61-year-old white woman with a history of end-stage renal disease on hemodialysis, paroxysmal atrial fibrillation not on long-term systemic anticoagulation, and history of recurrent diverticulitis that presented with acute onset abdominal pain and nausea. Computed tomography of her abdomen and pelvis with intravenous contrast was negative for acute intra-abdominal pathology, but incidentally identified an oval-shaped filling defect at the ostium of the coronary sinus suspicious for thrombus or mass which was confirmed on subsequent transesophageal echocardiogram. In light of her concomitant transaminitis but otherwise negative workup, the mass was believed to be thromboembolic in nature, originating within the hepatic venous system as a manifestation of recurrent diverticulitis with associated pylephlebitis and ultimately lodging into the coronary sinus. With the newly detected thrombus and history of paroxysmal atrial fibrillation, she was started on warfarin for therapeutic systemic anticoagulation that resolved her clot by 3-month follow up. CONCLUSIONS: Although coronary sinus thrombosis is rare, a high index of suspicion and close scrutiny of the venous system in patients with intra-abdominal infectious processes would prevent delay in management of this potentially serious complication. The discussion of this case highlights the anatomy of the cardiac venous system, the pathophysiology of thrombus formation, and the utility of transesophageal echocardiography in confirming a diagnosis and assessing treatment efficacy.

A randomized controlled trial to evaluate the effect of a new skincare regimen on skin barrier function in those with podoconiosis in Ethiopia.

BACKGROUND: Podoconiosis affects an estimated 3 million people in Ethiopia with a further 19 million at risk. Volcanic soil and pathogens enter skin breaches in the feet causing inflammation, lymphoedema and hyperkeratosis. There is no robust evidence on optimal podoconiosis skincare regimens to improve skin barrier function (SBF). OBJECTIVES: To evaluate the effectiveness of a new, low-cost, evidence-based intervention to improve SBF in the lower limbs of those with podoconiosis. METHODS: A randomized controlled trial (NCT02839772) was conducted over 3 months in two podoconiosis clinics (n = 193). The intervention comprised 2% (v/v) glycerine added to a reduced volume of soaking water. The control group received the current skincare regimen. Primary outcome measures were transepidermal water loss (TEWL) and stratum corneum hydration (SCH) at four specific sites on the lower limbs. RESULTS: Improvement in SBF was observed in both groups across all measurement sites and time points, although this was significantly greater in the experimental group. TEWL reduced in both groups at all sites. For example, on top of the foot the estimated group difference in TEWL at visit 4 was 1·751 [standard error (SE) = 0·0390] in favour of the experimental group [t = 3·15, degrees of freedom (df) = 189·58, P = 0·002, 95% confidence interval (CI) 0·066-2·85], indicating a greater reduction in TEWL in the experimental group. Similarly, at the same site the estimated group difference in SCH at visit 4 was -2·041 (SE = 0·572) in favour of the experimental group (t = -3·56, df = 186·74, P < 0·001, 95% CI -3·16 to -0·91), indicating a greater increase in SCH in the experimental group. There were also significantly greater reductions in odour, number of wounds and largest foot circumference in the experimental vs. the control group. CONCLUSIONS: The addition of 2% (v/v) glycerol to a reduced volume (83% reduction) of soaking water significantly improved SBF.

Livestock and feed water productivity in the mixed crop-livestock system.

Recently with limited information from intensified grain-based farming systems in developed countries, livestock production is challenged as being huge consumer of freshwater. The smallholder mixed crop-livestock (MCL) system which is predominant in developing countries like Ethiopia, is maintained with considerable contributions of crop residues (CR) to livestock feeding. Inclusion of CR is expected to reduce the water requirement for feed production resulting improvement in livestock water productivity (LWP). This study was conducted to determine feed water productivity (FWP) and LWP in the MCL system. A multistage sampling procedure was followed to select farmers from different wealth status. Wealth status dictated by ownership of key farm resources such as size of cropland and livestock influenced the magnitude of livestock outputs, FWP and LWP. Significant difference in feed collected, freshwater evapotranspired, livestock outputs and water productivity (WP) were observed between wealth groups, where wealthier are relatively more advantaged. Water productivity of CR and grazing land (GL) analyzed separately showed contrasting differences where better-off gained more on CR, whereas vice versa on GL. These counterbalancing of variations may justify the non-significant difference in total FWP between wealth groups. Despite observed differences, low WP on GL indicates the need of interventions at all levels. The variation in WP of CR is attributed to availability of production factors which restrained the capacity of poor farmers most. A linear relationship between the proportion of CR in livestock feed and FWP was evident, but the relationship with LWP was not likely linear. As CR are inherently low in digestibility and nutritive values which have an effect on feed conversion into valuable livestock products and services, increasing share of CR beyond an optimum level is not a viable option to bring improvements in livestock productivity as expressed in terms of LWP. Ensuring land security, installing proper grazing management, improved forage seed supply and application of soil and water conservation are expected to enhance WP on GL. Given the relationship of production factors with crop biomass and associated WP, interventions targeted to improve provision of inputs, credit, extension and training support due emphasis to the poor would increase CR yield and reduce part of water use for feed production. Optimizing feed value of CR with treatment and supplementation, following water efficient forage production methods and maintenance of healthy productive animals are expected to amplify the benefits from livestock and eventually improve LWP.

Renal function of MDR-TB patients treated with kanamycin regimens or concomitantly with antiretroviral agents.

SETTING: To compare renal insufficiency among multidrug-resistant tuberculosis (MDR-TB) patients treated with kanamycin (KM) based regimens and those treated concomitantly with tenofovir disoproxil fumarate (TDF) or other antiretroviral therapy (ART) regimens in Namibia. DESIGN: Retrospective review of the treatment records and laboratory tests of patients initiated on MDR-TB treatment (January-December 2014). The glomerular filtration rates (eGFR) estimated pre- and post-treatment were compared using the analysis of variance test. Renal insufficiency was defined as an eGFR of <60 ml/min/1.73 m2. Use of KM or TDF and association with renal insufficiency was assessed using Kaplan-Meier plots and Cox proportional hazards analysis. RESULTS: The baseline mean eGFR for the three groups was similar (P = 0.24): 139.3 ± 25.6 ml/min for the KM group (n = 68), 131.1 ± 25.7 ml/min for the KM+TDF group (n = 44) and 134.2±34.4 ml/min for the KM+Other group (n = 23). After 8 months, the values had declined significantly to respectively 104.8 ± 37.5 ml/min (P < 0.001), 101.5 ± 38.3 ml/min (P < 0.001) and 111.5 ± 41.7 ml/min (P = 0.01). Co-treatment with KM+ART was associated with an increased risk of renal insufficiency (hazard ratio [HR] 1.8, 95%CI 0.7-4.1, P = 0.20 for KM+TDF, and HR 3.5, 95%CI 1.4-8.2, P = 0.005 for KM+Other ART). CONCLUSION: Renal function declined at a similar rate in MDR-TB patients treated with KM-based regimens compared with patients treated concomitantly with TDF-based or other ART. The risk of renal insufficiency was greater for patients on ART.

Mitral Valve Perforation in Libman-Sacks Endocarditis: A Heart-Wrenching Case of Lupus.

Libman-Sacks (LS) endocarditis is one of the most common cardiac manifestations of systemic lupus erythematosus. Rarely, however, it can lead to serious complications, including severe valvular regurgitation or superimposed bacterial endocarditis. We describe the initial diagnostic challenges, clinical course, imaging studies and histopathological findings of a patient who presented with life-threatening lupus complicated by hemoptysis and respiratory failure secondary to a rare complication of LS endocarditis, acute mitral valve perforation. We review the current literature on valve perforation in the setting of LS endocarditis. In conclusion, although the disease is often asymptomatic and hemodynamically insignificant, it can result in serious and potentially fatal complications secondary to valve perforation, which may demand emergency surgical management.

Massive interventricular septal aneurysm and stroke in a healthy young patient: guilt by association?

Aneurysm of the membranous interventricular septum is an uncommon cardiac defect that is, on rare occasions, associated with embolic stroke. We describe here the case of an otherwise healthy, 41-year-old man who presented to the hospital with acute-onset confusion and left-sided body weakness attributed to a right middle cerebral artery ischemic stroke. He experienced a nearly complete resolution of deficits following systemic thrombolytic therapy. After an extensive workup, the presumed mechanism of stroke was a thromboembolus that originated in a massive aneurysm of the patient's membranous interventricular septum. Due to a perceived risk of surgical morbidity, the patient was managed conservatively with anticoagulation. He denied further events and reported nearly full function at follow-up.

Assessment of recovery, dreaming, hemodynamics, and satisfaction in postcardiac surgery patients receiving supplementary propofol sedation with S(+)-ketamine.

BACKGROUND: S(+)-ketamine is an analgesic and sedative drug with dissociative attributes. When it is used without sedatives, nightmares have been described. The aim of this study was to assess the effects of postoperative analgosedation with propofol and S(+)-ketamine when compared to standard propofol analgosedation in terms of recovery, dreaming, hemodynamics, and patient satisfaction. METHODS: Forty-eight patients were sedated with propofol (1-3 mg/kg/h) after coronary artery bypass grafting and allocated randomly on admission to the intensive care unit to receive either S(+)ketamine (2 mg mg/kg/h; group A) or 0.9% saline as a placebo (group B) in a double-blind fashion. If necessary, boli of 3.75 mg piritramide (an opioid) were given in both groups. RESULTS: Patients receiving S(+)-ketamine had significantly higher satisfaction for pain management (Visual Analog Scale [VAS] = group A: median 10 [range 9-10]; group B: median 9 [range 6-10]) despite their lower piritramide consumption. Patients receiving S(+)ketamine showed significantly faster eye opening (82+/-51 vs 156+/-110 min) but dreamed significantly more often (at 2 h, 67% in group A vs 29% in group B; at 24 h, 43% in group A vs 10% in group B), whereas no significant differences were detected in the incidence of nightmares at 2 h, 14% in group A vs 10% in group B; at 24 h, 5% in group A vs 5% in group B. CONCLUSIONS: Patients receiving S(+)-ketamine showed higher satisfaction for pain management and dreamed more often, but they did not have more nightmares.

Influence of continuous perioperative beta-blockade in combination with phosphodiesterase inhibition on haemodynamics and myocardial ischaemia in high-risk vascular surgery patients.

BACKGROUND: We sought to assess the intra- and postoperative haemodynamic effects of continuous perioperative beta-adrenergic blockade combined with phosphodiesterase (PDE) III inhibition and its potential benefits in limiting perioperative myocardial ischaemia in high-risk vascular surgery patients. METHODS: Seventy-five patients were randomly assigned to receive tight heart rate (HR) control by a continuous infusion of: esmolol in combination with the PDE III inhibitor enoximone (esmolol+enoximone group), esmolol infusion alone (esmolol group), or standard therapy (control group) for a period of 48 h. Myocardial ischaemia and dysfunction were detected by serial plasma Troponin T (TnT) and B-type natriuretic peptide (BNP) measurements. RESULTS: Cardiac index (CI) increased significantly only in esmolol+enoximone-treated patients [CI: from 2.4 (0.2) litre min(-1) m(-2) at baseline to 3.2 (0.2) litre min(-1) m(-2) at 24 h after surgery; P=0.001] and was significantly higher than in the esmolol [CI: from 2.5 (0.2) litre min(-1) m(-2) at baseline to 2.6 (0.2) litre min(-1) m(-2) at 24 h; P=0.18] and the control groups [CI: from 2.4 (0.2) litre min(-1) m(-2) at baseline to 2.7 (0.2) litre min(-1) m(-2) at 24 h; P=0.13]. A significant postoperative release of TnT was detected only in control patients. Plasma BNP levels increased towards the end of surgery in all patients. Peak plasma BNP concentrations were significantly higher in control patients [293 (98) pg ml(-1)] than in esmolol [118 (71) pg ml(-1)] and in esmolol+enoximone-treated patients [78 (21) pg ml(-1)]. CONCLUSIONS: Inotropic therapy with the PDE III inhibitor enoximone combined with tight HR control by a continuous infusion of esmolol improved cardiac function and reduced myocardial ischaemia in high-risk vascular surgery patients. CLINICAL TRIAL REGISTRATION INFORMATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00348101.

Influence on coagulation of a potato-derived hydroxethylstarch (HES 130/0.42) and a maize-derived hydroxethylstarch (HES 130/0.4) in patients undergoing cardiac surgery.

BACKGROUND: This study compared the effects of a potato-based hydroxyethyl starch (HES) with those of a maize-derived HES preparation on coagulation in cardiac surgery patients. METHODS: Sixty patients undergoing elective cardiac surgery with cardiopulmonary bypass were allocated randomly to receive either a potato-derived HES (6% HES 130/0.42) (n=30) or a waxy-maize-derived HES (6% HES 130/0.4) (n=30) given to keep pulmonary capillary wedge pressure/central venous pressure between 12 and 14 mm Hg until the second postoperative day (POD). A four-channel thrombelastography analyzer was used to measure rotation thrombelastometry (ROTEM) and whole blood aggregometry was used to assess the effects on platelet function. RESULTS: Potato HES 2990 (340) ml and maize HES 2890 (350) ml were given on the second POD. Standard coagulation (e.g. fibrinogen and antithrombin III) did not differ between the groups. Blood loss and need for transfusion of blood/blood products did not differ. Coagulation time (intrinsic/extrinsic CT) and clot formation time (intrinsic/extrinsic CFT) increased similarly after surgery and after 5 h, but recovered completely by the first and second POD. Clot firmness was similar in both groups. Platelet function induced by three inductors decreased significantly after surgery, but without significant differences between the two groups. Platelet function had recovered fully by the first POD. CONCLUSIONS: Both HES preparations showed similar effects on thrombelastometry and platelet function. As blood loss and need for the use of blood products were also similar, both potato- and maize-derived HES preparations can be safely used in cardiac surgery with regard to haemostasis.

Whole-blood aggregometry: are there any limits with regard to platelet counts?

BACKGROUND: Whole-blood aggregometry (WBA) is a promising tool to assess platelet function in its physiological environment. Dilution of whole blood in WBA disregards platelet concentrations that may impact the results, especially in the case of low platelet counts. In a blinded, prospective in vitro study, the influence of platelet concentrations on WBA was assessed. METHODS: Aggregation studies were carried out using whole blood from 10 healthy volunteers adjusted to platelet concentrations of 150, 100, 75, 50 and 25/nl using a plasma-balanced crystalloid solution. Platelet aggregation was measured by a new near-side whole blood aggregometer, activated by adenosin-diphosphate, collagen and thrombin-receptor activating protein. Three different approaches were applied: P1: whole blood diluted by an isotonic saline solution before activation, P2: undiluted whole blood with the single and P3: with the twofold concentration of the stimulating agent. RESULTS: Aggregometry in diluted whole blood (P1) decreased significantly from a platelet concentration of 100/nl (P<0.01). In undiluted whole blood, aggregation declined significantly from concentrations of 75 and 50/nl for P2 and P3 (P<0.01). No correlation to platelet count occurred in the undiluted approaches until a platelet concentration of 75/nl, whereas correlation in the diluted test run was detected starting from 100/nl. CONCLUSIONS: This study demonstrates that WBA depends on the platelet count and sensitivity towards low platelet concentrations may be improved by abdication of further dilution and the use of undiluted whole blood.

Is albumin administration in hypoalbuminemic elderly cardiac surgery patients of benefit with regard to inflammation, endothelial activation, and long-term kidney function?

BACKGROUND: Because patients with low albumin levels may benefit from human albumin (HA) administration, we studied correction of hypovolemia with HA in hypoalbuminic elderly cardiac surgery patients. METHODS: In a prospective, randomized study, 50 patients aged >80 yr undergoing cardiac surgery using cardiopulmonary bypass with a preoperative serum albumin concentration of <3.5 mg/dL, received either 5% HA (n = 25) or hydroxyethyl starch (6% HES 130/0.4) (n = 25). Volume was added to the priming (500 mL) and given until the morning of the second postoperative day to keep pulmonary capillary wedge pressure or central venous pressure between 12 and 14 mm Hg. RESULTS: Inflammatory response (interleukins-6, -10), endothelial activation (intercellular adhesion molecule-1), and kidney function (including glutathione transferase-alpha and neutrophil gelatinase-associated lipocalin) were measured after induction of anesthesia, 5 h after surgery, and the first and second postoperative day. A follow-up, approximately 60 days after discharge from the hospital, was done. Two thousand nine hundred eighty +/- 430 mL of HA and 3060 +/- 680 mL of HES 130/0.4 were given. Serum albumin concentration was significantly increased by HA (to 4.5 +/- 0.3 mg/dL). Serum creatinine, glomerular filtration rate, and urinary levels of alpha-glutathione transferase and neutrophil gelatinase-associated lipocalin were not different in the HA-compared to the HES-treated patients. The inflammatory response was similar in both groups, whereas endothelial activation was less in the HES group. None of the patients developed renal failure requiring renal replacement therapy. CONCLUSION: Use of HA in hypoalbuminemic cardiac surgery patients aged >80 yr was without benefit with regard to inflammatory response, endothelial activation, and renal function compared to 6% HES 130/0.4.

Individual titration of propofol plasma target improves anaesthetic stability in patients undergoing major abdominal surgery: a comparison with manually controlled infusion.

BACKGROUND AND OBJECTIVE: The impact of anaesthesia using target-controlled infusion with propofol on intraoperative stability, recovery and cost compared to manually controlled infusion has been evaluated with inconsistent results. We studied a new device that allows more individual titration of propofol target-controlled infusion by using the effect-site concentration at the loss of eyelash reflex to predict the maintenance infusion rate (FM-TCI). METHODS: Fifty-six patients undergoing major abdominal surgery lasting >2 h were randomly assigned to receive either FM-TCI (n = 28) or MCI-controlled (n = 28) anaesthesia. Both groups were Bispectral Index-monitored and thoracic epidural analgesia was established. Anaesthetic stability, incidence of haemodynamic abnormalities, time to extubation, propofol consumption and patient satisfaction were assessed. RESULTS: In the FM-TCI group, a significantly improved anaesthetic stability was achieved (0.43 +/- 0.44 vs. 1.31 +/- 0.78 adjustments of propofol infusion per patient per hour, P = 0.003) and time to extubation was significantly shorter (9.6 +/- 2.1 vs. 15.7 +/- 9.6 min P = 0.011). With FM-TCI, propofol consumption was significantly lower. Haemodynamic stability and patient satisfaction did not differ between the groups. CONCLUSION: FM-TCI helps to provide more stable anaesthesia conditions requiring less-frequent adjustments of the propofol infusion compared to manually controlled infusion in patients undergoing major abdominal surgery.

Comparison of the effects of gelatin and a modern hydroxyethyl starch solution on renal function and inflammatory response in elderly cardiac surgery patients.

BACKGROUND: The effects of hydroxyethylstarch (HES) 130/0.4 6% and gelatin 4% on inflammation, endothelial integrity, and renal function after cardiac surgery were compared. METHODS: Sixty patients aged >80 yr undergoing cardiac surgery were randomized to receive gelatin (n=30) or HES 130/0.4 (n=30). The colloid was used in the priming of the cardiopulmonary bypass circuit (500 ml) and for volume replacement until the second postoperative day (POD). Serum creatinine, creatinine clearance, IL-6, IL-10, intercellular adhesion molecule-1 (sICAM-1), urinary glutathione transferase-alpha, and neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Serum creatinine was also reported approximately 60 days after discharge. RESULTS: The mean(sd) volume of gelatin infused was 4180(440) ml, which was greater than the volume of HES infused 2910(330) ml (P=0.002). The mean(sd) volume of serum creatinine on the first POD was 151(24) micromol litre(-1) in the gelatin group and 126(13) micromol litre(-1) in the HES group (P=0.004). Values for the second POD were 161(0.26) and 133(16) micromol litre(-1), respectively (P=0.004). Creatinine clearance was lower in the gelatin group on the first POD [37(7) vs 46(8) ml min(-1) 1.73 m2 (P=0.004)] and the second POD [32(8) vs 45(10) ml min(-1) 1.73 m2 (P=0.002)]. Kidney function approximately 60 days after discharge did not differ between the groups. IL-6, IL-10, and sICAM-1 were significantly lower in the HES group than in the gelatin group on the first and second PODs. Urinary alpha-GST increased in both groups to a comparable extent. Urinary NGAL concentrations were higher in the gelatin than in the HES patients 5 h after surgery and on the first and second PODs. CONCLUSIONS: In cardiac surgery patients aged >80 years, volume therapy with HES 130/0.4 6% was associated with less marked changes in kidney function and a less marked endothelial inflammatory response than gelatin 4%.

The impact of a medium molecular weight, low molar substitution hydroxyethyl starch dissolved in a physiologically balanced electrolyte solution on blood coagulation and platelet function in vitro.

BACKGROUND AND OBJECTIVES: Hydroxyethyl starches (HES) may have the potential to impact negatively on haemostasis. Recent findings suggest that side-effects on haemostasis stem not only from the physicochemical differences between HES, but also from the composition of the solvent. We compared the effects of a newly developed medium molecular weight (MW) and low molar substitution (MS) HES dissolved in a physiologically balanced electrolyte solution (MW 130, MS 0.42; B-HES) with a commercially available non-balanced HES (MW 130, MS 0.4; NB-HES), and with Ringer's lactate (RL) solution in vitro. MATERIALS AND METHODS: Activated partial thromboplastin time (APTT), factor VIII clotting activity (F VIII:C) and von Willebrand factor (vWF) activity were investigated in 48 healthy individuals. Platelet function as measured by turbidimetric platelet aggregometry and whole blood impedance aggregometry induced by adenosine diphosphate (ADP), collagen and thrombin receptor activating peptide (TRAP), and by ADP and TRAP-induced expression of activated platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa was determined in 24 participants. Haemodilution (25% and 50%, v/v for blood coagulation analyses and 20% and 40%, v/v for platelet function studies) was performed using the two HES preparations and RL. RESULTS: APTT was significantly longer and F VIII and vWF significantly lower at 25% and 50% dilutions with NB-HES compared to B-HES and RL. At 20% and 40% dilutions, ADP and TRAP-induced expression of activated platelet surface GP IIb/IIIa was significantly increased by B-HES compared to NB-HES and RL. Percentages of platelet GP IIb/IIIa expression were also significantly greater in samples diluted with B-HES than in undiluted blood. Neither the diluent (B-HES, NB-HES and RL) nor the degree of dilution (undiluted, 20% and 40% dilution) had any significant influence on ADP, collagen or TRAP-induced turbidimetric platelet aggregation or impedance platelet aggregation. CONCLUSIONS: In contrast to a non-balanced 130 kDa, MS 0.4 HES (NB-HES), a 130 kDa, MS 0.42 HES preparation dissolved in a physiologically balanced electrolyte solution (B-HES) does not affect APTT, F VIII:C and vWF in vitro. Both types of HES do not affect platelet aggregation induced by ADP, collagen or TRAP. B-HES but not NB-HES increases the expression of activated platelet GP IIb/IIIa induced by ADP or TRAP.