Hemodilution on Cardiopulmonary Bypass: Thromboelastography Patterns and Coagulation-Related Outcomes.

OBJECTIVE: Hemodilution has been associated with both hypocoagulability and hypercoagulability in studies based on thromboelastography (TEG). Severe hemodilution during cardiopulmonary bypass (CPB) is a risk factor for morbidity in cardiac surgery. This study investigated the effects of different degrees of hemodilution with CPB on post-CPB TEG parameters and coagulation-related outcomes. DESIGN: Retrospective cohort study. SETTING: University research hospital. PARTICIPANTS: The study comprised 793 cardiac surgery patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The patient population was divided into low (LH), moderate (MH), and severe (SH) hemodilution groups based on the hemodilution degree on CPB. Differences in TEG parameters and coagulation-related outcomes were assessed. Patients with SH experienced significantly (p = 0.019) prolonged clotting times (median r-time 6.1 min, interquartile range 5.1-7.4 min) with respect to patients with MH (median r-time 5.8 min, interquartile range 4.8-7 min) and LH (median r-time 5.9 min, interquartile range 4.8-7.2 min). Clot firmness was significantly (p = 0.001) lower in patients with SH (median maximum amplitude 63 mm, interquartile range 57-68 mm) compared with patients with MH (median maximum amplitude 65 mm, interquartile range 61-71 mm) and LH (median maximum amplitude 67 mm, interquartile range 62-74 mm). Patients with SH had higher chest drain blood loss and required more fresh frozen plasma and platelet concentrate transfusions than did patients with MH or LH. Postoperative thromboembolic complications were significantly (p = 0.006) more common in patients with SH (2.6%) than in patients with MH (0%) or LH (0.4%). CONCLUSIONS: SH on CPB is associated with hypocoagulation, bleeding, and thrombosis-associated worse outcomes.

Association of Obesity-Related Hemodilution of Prostate-Specific Antigen, Dihydrotestosterone, and Testosterone.

BACKGROUND: Prostate-specific antigen (PSA) hemodilution is the leading theory for lower PSA values in obese men. However, testosterone and dihydrotestosterone (DHT), which are necessary for PSA production, are reduced in obese men. We assessed the relationship of body mass index (BMI) and PSA, taking into consideration the effect of testosterone and DHT. METHODS: Among 8,122 participants in Reduction by Dutasteride of Prostate Cancer Events (REDUCE), complete data were available for 7,275. BMI was categorized as normal (<25 kg/m2 ), overweight (25-29.9 kg/m2 ), obese (30-34.9 kg/m2 ), or moderate + severely obese (≥35 kg/m2 ). Associations between BMI, testosterone, and DHT and the outcome variable of PSA were examined using linear regression. RESULTS: There were 1,964 (27.0%) normal weight, 3,826 (52.6%) overweight, 1,200 (16.5%) obese, and 285 (3.9%) moderately + severely obese patients. With increasing BMI, there was a progressive decrease in PSA (P = 0.02), increase in prostate volume (P < 0.001), and decrease in both testosterone (P < 0.001) and DHT (P < 0.001). Using linear regression, increasing BMI was associated with decreasing serum PSA values. Furthermore, BMI remained inversely associated with PSA after individually adjusting for testosterone and DHT, as well as when adjusting for testosterone and DHT in the same model. Decreased androgen levels accounted for only 19% of the lower PSA in men with higher BMI. CONCLUSIONS: Only a fraction of lower PSA in obese men could be attributed to testosterone and DHT levels. The remaining factors explaining lower PSA are unaccounted for, presumably secondary to hemodilution associated with increased plasma volume in obese men. Prostate 77:466-470, 2017. © 2016 Wiley Periodicals, Inc.

Acute Normovolemic Hemodilution Reduces Allogeneic Red Blood Cell Transfusion in Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: To better understand the role of acute normovolemic hemodilution (ANH) in a surgical setting with high risk of bleeding, we analyzed all randomized controlled trials (RCTs) in the setting of cardiac surgery that compared ANH with standard intraoperative care. The aim was to assess the incidence of ANH-related number of allogeneic red blood cell units (RBCu) transfused. Secondary outcomes included the rate of allogeneic blood transfusion and estimated total blood loss. METHODS: Twenty-nine RCTs for a total of 2439 patients (1252 patients in the ANH group and 1187 in the control group) were included in our meta-analysis using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE. RESULTS: Patients in the ANH group received fewer allogeneic RBCu transfusions (mean difference = -0.79; 95% confidence interval [CI], -1.25 to -0.34; P = .001; I = 95.1%). Patients in the ANH group were overall transfused less with allogeneic blood when compared with controls (356/845 [42.1%] in the ANH group versus 491/876 [56.1%] in controls; risk ratio = 0.74; 95% CI, 0.62 to 0.87; P < .0001; I = 72.5%), and they experienced less postoperative blood loss (388 mL in ANH versus 450 mL in control; mean difference = -0.64; 95% CI, -0.97 to -0.31; P < .0001; I = 91.8%). CONCLUSIONS: ANH reduces the number of allogeneic RBCu transfused in the cardiac surgery setting together with a reduction in the rate of patients transfused with allogeneic blood and with a reduction of bleeding.

Ideal Hematocrit to Minimize Renal Injury on Cardiopulmonary Bypass.

OBJECTIVE: Renal dysfunction after cardiopulmonary bypass (CBP) ranges from subclinical injury to established renal failure requiring dialysis. The pathophysiology is multifactorial, and recently, hemodilution during CBP has been thought to be an important determinant of postoperative renal injury. In this study, we attempted to assess the independent effect of hemodilution on renal function. We also aimed to identify the optimal hematocrit where hemodilution-induced renal injury is minimal. METHODS: A prospective observational study was conducted on 200 patients between February 2012 and July 2013. One hundred fifty patients were included in the study group, who were further subdivided on the basis of lowest hemodilution as mild hemodilution (>25%), moderate hemodilution (21%-25%), and severe hemodilution (<21%) categories. The primary outcome of the study was renal outcome measure, which was assessed by comparing the creatinine clearance across the groups. RESULTS: The creatinine clearance decreased over a period in all three groups. When compared with mild or moderate hemodilution, the reduction in creatinine clearance was significantly higher in the group with severe hemodilution (P ≤ 0.0001). However, there was no significant difference in creatinine clearance reduction between the mild and moderate hemodilution groups (P = 0.813; 95% confidence interval, -8.41 to 10.68). CONCLUSIONS: Based on our observations, we would like to propose that a hematocrit of 21% should be considered the critical threshold. Hematocrit below this value of 21% during CBP is associated with the most significant deterioration in renal function.

The evolving role of hemodilution in treatment of cerebral vasospasm: a historical perspective.

OBJECTIVE: Hypertension, hypervolemia, and hemodilution [HHH] therapy is widely used for prophylactic and therapeutic means in the setting of angiographic or clinical cerebral vasospasm. Hemodilution remains the most controversial aspect of the HHH therapy. METHODS: We performed a literature review to identify the current state of support for hemodilution as a therapeutic modality in treatment of cerebral vasospasm. RESULTS: Over time, evidence has been accumulating against the efficacy of HHH therapy and hemodilution in particular. Although HHH therapy and consequently hemodilution has wide support, the evidence for its effectiveness remains equivocal. CONCLUSIONS: At the time of this study, the burden of evidence appears to be tipped away from hemodilution as a therapeutic modality.

La obesidad modifica el antígeno prostático específico en hombres mayores de 45 años de edad / Obesity modifies prostatic specific antigen in men over 45 year

OBJETIVO: Determinar si las menores concentraciones séricas de antígeno prostático específico (PSA) encontradas en los sujetos obesos son consecuencia de bajos niveles de testosterona circulante y/o del mayor volumen plasmático (-VP- hemodilución).MÉTODOS: Fueron seleccionados 413 individuos de sexo masculino entre 45 y 75 años. El trabajo consistió en una evaluación de la composición corporal mediante antropometría (medición de peso y talla y cálculo del índice de masa corporal –IMC-, superficie corporal- SC- y VP), estimación de peso prostático por ecografía transrectal (ETR) y un análisis de laboratorio incluyendo dosaje de la PSA total y, en un subgrupo de pacientes (n= 108), determinación de la concentración sérica de testosterona. Se calculó la masa de PSA circulante (PSA masa). El análisis estadístico se realizó mediante Anova I y el coeficiente de correlación de Pearson (p<0.05).RESULTADOS: La edad promedio fue de 59,08 años y la media de IMC de 28,80 kg/m2. Los sujetos con IMC entre 20-24,9 kg/m2 (n= 68) presentaron una media de PSA de 1,43 ng/ml; en los voluntarios con sobrepeso (n=222), IMC entre 25-29,9 kg/m2, la media encontrada de fue de 1,40 ng/ml; en los obesos tipo I (n=114), IMC entre 30-39,9 kg/m2, se halló una PSA media de 1,05 ng/ml y finalmente en los obesos tipo II (n= 9), IMC > 40 kg/m2 , el PSA tuvo un valor medio de 0,85 ng/ml. Un mayor IMC se asoció significativamente con un mayor VP (r= 0,687; p =0,001) y con una menor concentración sérica de PSA (r= -0,235; p= 0,001). Por su parte, el PSA masa fue menor en los pacientes obesos tipo I y II que en los voluntarios con sobrepeso y normopeso aunque estadísticamente no significativo ( p<0.063). El peso prostático y los niveles de testosterona fueron similares en todos los voluntarios independientemente del estado nutricional que presentaran(AU)

CONCLUSIÓN: La principal causa de menor concentración de PSA en sujetos obesos sería la hemodilución por mayor volumen plasmático; sin embargo, también hay una discreta reducción en la secreción de proteína PSA en estos sujetos aunque no estaría relacionada bajos niveles de testosterona(AU)

OBJECTIVES: To determine whether lower serum prostate-specific antigen (PSA) concentration in obese men is caused by plasma hemodilution and/or decreased serum testosterone levels.METHODS: A sample of 413 men, from 45 to 75 years old, were randomly selected for the study among those who participated in prostate cancer screening at 2 urban urology practices in Argentina and Puerto Rico. Weight, height, serum testosterone and total PSA concentration were determined. Body mass index (BMI), body surface, plasma volume, and PSA mass were calculated. Prostate volume was estimated by transrectal ultrasound using the prolate ellipsoid formula.RESULTS: Mean age was 59 years old (range, 45 to 75) and mean BMI was 28.8 kg/m2 (range, 24 to 46). Mean serum PSA concentration was 1.43 ng/ml in normal weight patients (n=68), 1.4 ng/ml in overweight patients (n=222), 1.05 ng/ml in obese patients (n=114), and 0.85 ng/ml in morbidly obese patients (n=9). BMI was directly correlated with plasma volume (r= 0.687; p= 0.001) and inversely correlated with serum PSA concentration (r= -0.235; P= 0.001). PSA mass tended to be lower in obese and morbidly obese patients (P= 0.0063) compared to normal weight and overweight subjects. Serum testosterone concentration (P= 0.91) and prostate volume (P= 0.068) were similar among all BMI groups.CONCLUSIONS: Obese men had lower serum PSA concentrations than normal weight men mainly due to plasma hemodilution. PSA mass tended to be lower in obese patients, but it is unlikely a consequence of lower serum testosterone concentrations(AU)

Fundamentos básicos para el empleo de hemoderivados y estrategias de ahorro de sangre en cirugía / No disponible

La exposición de pacientes a una transfusión alogénica puede ser minimizadamediante técnicas de conservación de sangre (autotransfusiónpreoperatoria, hemodilución aguda normovolémica, recuperación celular),corrección de la anemia preoperatoria con agentes eritropoyéticos(hierro y/o eritropoyetina) y empleo de agentes farmacológicos, comoconcentrado de factores de coagulación (e.j. el factor VII activo recombinante)y antifi brinolíticos. En general, una política transfusional restrictivaes más benefi ciosa que una estrategia liberal(AU)

Exposure of patients to allogeneic blood transfusion can be minimized oravoided by systematic use of blood conservation techniques (autologousblood donation, acute normovolemic hemodilution or blood cell salvage),correction of preoperative anemia with erythropoietic agents (iron and/orerythropoietin), and pharmacological agents, such as recombinant factorVII and antifi brinolytics. In general, restrictive versus liberal transfusionis preferred in most patients(AU)

Acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4) reduces focal cerebral ischaemic injury in rats.

BACKGROUND AND OBJECTIVES: This study investigated the neuroprotective effect of acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4, HES) on focal cerebral ischaemia-reperfusion injury and determined optimum degree for haemodilution in the rat. METHODS: Male Sprague-Dawley rats were randomly divided into three groups (n = 10 each): hydroxyethyl starch, saline and controls. Animals in the hydroxyethyl starch and saline groups were haemodiluted until haematocrit decreased to 30% of baseline. In another experiment male Sprague-Dawley rats were randomly assigned to four groups (n = 10 each): HES30, HES25 and HES20 and controls. Rats in the HES30, HES25 and HES20 groups were haemodiluted with hydroxyethyl starch until the haematocrit decreased to 30%, 25% and 20%, respectively. At 15 min after haemodilution, all the rats were subjected to a right middle cerebral artery occlusion for 120 min. Neurologic deficit scores and infarct volumes were assessed 24 h after reperfusion. RESULTS: Haemodilution with hydroxyethyl starch improved neurologic outcome (P < 0.01) and reduced infarct volume (P < 0.01) compared to saline and controls. Haemodilution with saline augmented infarct volume (P < 0.05 vs. controls). Neurologic deficit scores in HES30 and HES25 groups were significantly lower compared to controls (P < 0.05) while infarct volumes in controls and HES20 were significantly larger compared to HES30 and HES25 (P < 0.01). CONCLUSIONS: This study demonstrates that acute normovolaemic haemodilution with a novel hydroxyethyl starch (130/0.4) reduces infarct volume and improves neurological outcome after focal cerebral ischaemia in a rat stroke model. Neuroprotection by haemodilution was highest at haematocrit dilution between 25% and 30%, while ischaemic injury was exacerbates when haematocrit was diluted to 20%.

[Central and branch retinal vein occlusion. Current strategies for treatment in Germany, Austria and Switzerland]. / Retinale Zentralvenen- und Venenastverschlüsse: Aktueller Therapiestand in Deutschland, Osterreich und der Schweiz.

BACKGROUND: The main object of this study was to find out what treatment methods are currently preferred for central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) in Germany, Austria and Switzerland. METHODS: A questionnaire concerning the different medicamentous, surgical and laser treatments available for CRVO and BRVO was developed and sent out to the members of the German Retina Society. RESULTS: This analysis is based on 124 returned questionnaires. We found that 64% of our colleagues recommend isovolemic hemodilution in patients with CRVO. Pentoxyfyllin infusions are endorsed by 32% and 27%, respectively, for CRVO and BRVO. Panretinal photocoagulation is applied only if neovascularization is present by 39% of those responding, whereas 61% perform prophylactic photocoagulation when there is no visible neovascularization, depending on the degree of ischemia. In the case of macular edema due to BRVO 52% recommend macular grid photocoagulation. Sheathotomy is recommended by 51% for BRVO suggest, and 43% advise radial optic neurotomy (RON) for CRVO. Intravitreal injection of triamcinolone is performed for CRVO or BRVO by 58% and 56%, respectively, and para-bulbar injection of triamcinolone by 2% and 3%. Intravitreal anti-VEGF treatment is applied by 72% of respondents, the majority (94%) using bevacizumab for this purpose. CONCLUSION: Members of the German Retina Society apply widely differing treatments in patients with CRVO and BRVO. Further clinical studies to evaluate the different therapeutic options seem necessary in order to set up guidelines for the treatment of venous retinal occlusions.

Seguridad del Haemaccel/Solucel en pacientes sometidos a hemodilución normovolémica intencional preoperatoria (Estudio multicéntrico internacional)

El uso de Haemaccel/Soluccel en 305 pacientes sometidos a hemodilución preoperatoria normovolémica intencional, ha sido documentada en un estudio abierto, prospectivo, multicéntrico, controlado y multinacional (doce centros en 5 países). Los hallazgos reproducen el índice bajo de efectos adversos encontrados en la literatura corriente

Ischemic stroke: today and tomorrow.

OBJECTIVE: To review selected aspects of the current treatment of acute ischemic stroke and provide an overview of basic neuroscience research in cerebral ischemia that may be applicable to future therapies. DATA SOURCES: Selected recent references dealing with current therapy of acute stroke and basic neuroscience developments in cerebrovascular disease from the past several years. STUDY SELECTION/DATA EXTRACTION: Whenever possible, recommendations concerning treatment were based on results of clinical trials; when such data were lacking, the authors present possible treatment approaches. DATA SYNTHESIS: Acute stroke is a heterogeneous process involving different etiologic mechanisms. Different types of stroke, however, may produce a similar cascade of physiologic and biochemical events leading to tissue damage. Calcium flux, glutamate excitotoxicity, platelet and leukocyte activation, free radical formation, and nitric oxide metabolism may be crucial focal points of future stroke therapy. CONCLUSIONS: Recent clinical trials have given scientific basis for some of our treatment approaches to ischemic stroke. Future treatments for stroke will likely focus on factors which modulate biochemical events occurring as a final common pathway to all forms of cerebral ischemia.