Severe Hemodilution Research Articles

Intraoperative haemofiltration during on-pump cardiac surgery at Queen Alia Heart Institute

Background: Objective of the study was to determine the frequency, indications and benefits of utilizing haemofiltration during cardiopulmonary bypass in adult cardiac surgical patients. Methods: This is a prospective observational analysis of data of adult cardiac surgical patients presented for on-pump cardiac surgery in the period between September 2023 and December 2023 at Queen Alia Heart Institute. Data was collected using Google Forms online and was subsequently recorded on Excel sheaths. Patients were divided into two groups: the haemofiltration group and the non-haemofiltration group. Both groups were compared according to perioperative laboratory and clinical variables. Statistical analysis of results using Microsoft excel followed data collection. Ethical committee approval was obtained. Results: Data from 130 adult cardiac surgical patients (105 males and 25 females) enrolled in this analysis showed that haemofiltration was used in 25 patients (19.2%). The most frequent indication for intraoperative haemofiltration was haemodilution in 14 patients (56%). Blood transfusion was needed in 17 (68%) of patients who had haemofiltration and in 35 (33.4%) of patients who did not need haemofiltration. Patients from the haemofiltration group were extubated 5 hours earlier than patients from the non-haemofiltration group, as the duration of mechanical ventilation in the ICU was 17.9 hours in the haemofiltration group versus 24.9 hours in the non-haemofiltration group. The average overall hospital stay was 3 days less in the haemofiltration group. Conclusions: Haemofiltration during cardiopulmonary bypass main indications were severe haemodilution, hyperkalaemia and preoperative renal impairment. The use of haemofiltration during CPB was associated with earlier tracheal extubation and shorter hospital stay.

Effect of nadir hematocrit during cardiopulmonary bypass on the early outcomes after surgical repair of acute type A aortic dissection

Although hemodilution during hypothermic cardiopulmonary bypass (CPB) had been thought to improve microcirculation and reduce blood viscosity, there has been no report investigating the effect of low nadir hematocrit (Hct) values caused by severe hemodilution on the surgical outcomes of patients with acute type A aortic dissection (ATAAD). We retrospectively reviewed 112 consecutive patients who emergently underwent emergency surgical repair of ATAAD at our institution. The patients were classified into the high Hct (nadir Hct ≥ 21% during CPB; n = 51) and low Hct (nadir Hct < 21% during CPB; n = 61) groups. After propensity score matching of preoperative characteristics, surgical outcomes were compared between the groups. Although there was no difference in the surgical procedure, longer CPB time and more blood transfusion during surgery were needed in the low Hct group than in the high Hct group. After surgery, estimated glomerular filtration rate was significantly lower (p = .015), lactaic acid was higher (p = .045), and intubation time was longer (p = .018) in the low Hct group than in the high Hct group, although there was no difference in hospital mortality between the groups. The AUC of the nadir Hct during CPB as a prognostic indicator of prolonged postoperative ventilator support was 0.8, with the highest accuracy at 16.7% (sensitivity 88%, specificity 76.9%). In all cohorts, female sex was an independent risk factor for a lower nadir Hct value of <21% during CPB. A lower nadir Hct value of <21% during CPB may be associated with postoperative renal dysfunction and prolonged ventilator support in patients with ATAAD.

Intraosseous infusion of liposome-encapsulated hemoglobin (HbV) acutely prevents hemorrhagic anemia-induced lethal arrhythmias, and its efficacy persists with preventing proarrhythmic side effects in the subacute phase of severe hemodilution model.

Artificial oxygen carriers (HbV) can treat hemorrhagic shock with lethal arrhythmias (VT/VF). No reports exist on subacute HbV's effects. Acute and subacute resuscitation effects with anti-arrhythmogenesis of HbV were studied in 85% blood exchange rat model (85%-Model). Lethal 85%-Model was created by bone marrow transfusion and femoral artery bleeding in 80 SD rats in HbV-administered group (HbV-group), washed erythrocyte-administered group (wRBC-group), and 5% albumin-administered group (ALB-group). Survival rates, anti-arrhythmic efficacy by optical mapping system (OMP) with electrophysiological study (EPS) in Langendorff heart, cardiac autonomic activity by heart rate variability (HRV) and ventricular arrhythmias by 24-h electrocardiogram telemetry monitoring (24h-ECG) in awake, and left ventricular function by echocardiography (left ventricular ejection fraction [LVEF]) were measured. All rats in HbV- and wRBC-groups survived for 4 weeks, whereas no rats in ALB-group. HbV and wRBC acutely suppressed VT/VF in Langendorff heart through ameliorating action potential duration dispersion (APDd) analyzed by OMP with EPS. For subacute analysis, 50% blood exchange by 5% albumin was used (ALB-group 50). Subacute salutary effect on APDd and VT/VF inducibility was confirmed in HbV- and wRBC-groups. 24h-ECG showed that HbV and wRBC suppressed none-sustained ventricular tachycardia (NSVT) and sympathetic component of HRV (LF/HF) with preserved LVEF (HbV-group, wRBC-group vs. ALB-group 50; NSVT numbers/days, 0.5±0.3, 0.4±0.3 vs. 3.9±1.2*; LF/HF, 1.1±0.2, 0.8±0.2 vs. 3.5±1.0*; LVEF, 84±5, 83±4, vs. 77±4%*; *p<0.05). Collectively, HbV has sustained antiarrhythmic effect in subacute 85%-Model by ameliorating electrical remodeling and improving arrhythmogenic modifying factors (HRV and LVEF). These findings are useful in now continuing clinical trials of HbV.

Hydroxyl Ethyl Starch (HES) Preserves Intrarenal Microcirculatory Perfusion Shown by Contrast-Enhanced Ultrasound (Ceus), and Renal Function in a Severe Hemodilution Model in Pigs.

Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of blood and purposed to cause renal injury in perioperative setting. It is best accomplished in a perioperative setting by a colloid such as hydroxyl ethyl starch (HES) due its capacity to fill the vascular compartment and maintain colloidal pressure. However, alterations of intra renal microvascular perfusion, flow and its effects on renal function and damage during ANH has not been sufficiently clarified. Based on the extensive use of HES in the perioperative setting we tested the hypothesis that the use of HES during ANH is able to perfuse the kidney microcirculation adequately without causing renal dysfunction and injury in pigs. Hemodilution (n = 8) was performed by stepwise replacing blood with HES to hematocrit (Hct) levels of 20% (T1), 15% (T2), and 10% (T3). Seven control animals were investigated. Systemic and renal hemodynamics were monitored. Renal microcirculatory perfusion was visualized and quantified using contrast-enhanced ultrasound (CEUS) and laser speckle imaging (LSI). In addition, sublingual microcirculation was measured by handheld vital microscopy (HVM). Intrarenal mean transit time of ultrasound contrast agent (IRMTT-CEUS) was reduced in the renal cortex at Hct 10% in comparison to control at T3 (1.4 ± 0.6 vs. 2.2 ± 0.7 seconds, respectively, P < 0.05). Although renal function was preserved, the serum neutrophil gelatinase-associated lipocalin (NGAL) levels was higher at Hct 10% (0.033 ± 0.004 pg/μg protein) in comparison to control at T3 (0.021 ± 0.002 pg/μg protein. A mild correlation between CO and IRMTT (renal RBC velocity) (r -0.53; P = 0.001) and CO and NGAL levels (r 0.66; P = 0.001) was also found. Our results show that HES induced ANH is associated with a preserved intra renal blood volume, perfusion, and function in the clinical range of Hct (<15%). However, at severely low Hct (10%) ANH was associated with renal injury as indicated by increased NGAL levels. Changes in renal microcirculatory flow (CEUS and LSI) followed those seen in the sublingual microcirculation measured with HVM.

Effects of different plasma expanders on rats subjected to severe acute normovolemic hemodilution

BackgroundPlasma expanders are widely used for acute normovolemic hemodilution (ANH). However, existing studies have not focused on large-volume infusion with colloidal plasma expanders, and there is a lack of studies that compare the effects of different plasma expanders.MethodsThe viscosity, hydrodynamic radius (Rh) and colloid osmotic pressure (COP) of plasma expanders were determined by a cone-plate viscometer, Zetasizer and cut-off membrane, respectively. Sixty male rats were randomized into five groups with Gelofusine (Gel), Hydroxyethyl Starch 200/0.5 (HES200), Hydroxyethyl Starch 130/0.4 (HES130), Hydroxyethyl Starch 40 (HES40), and Dextran40 (Dex40), with 12 rats used in each group to build the ANH model. ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders. Acid-base, lactate, blood gas and physiological parameters were detected.ResultsGel had a lower intrinsic viscosity than HES200 and HES130 (P < 0.01), but at a low shear rate in a mixture of colloids, red cells and plasma, Gel had a higher viscosity (P < 0.05 or P < 0.01, respectively). For hydroxyethyl starch plasma expanders, the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of Rh from 10.7 nm to 20.2 nm. A severe ANH model, with the hematocrit of 40% of the baseline level, was established and accompanied by disturbances in acid-base, lactate and blood gas parameters. At the end of ANH and 60 min afterward, the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly in all groups at the end of ANH. The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH. During the process of ANH, the Dex40 group showed a drop and recovery in SBP, DBP and MAP. The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points (P < 0.05 or P < 0.01).ConclusionGel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates. Rh and COP showed a strong correlation among hydroxyethyl starch plasma expanders. Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders. During the process of ANH, Dex40 displayed a V-shaped recovery pattern for blood pressure, and HES200 had the advantage in sustaining the DBP and MAP at some time points.

A randomised controlled comparison of aspiration and non-aspiration fine-needle techniques for obtaining ultrasound-guided cytological samples from canine livers

Ultrasound-guided fine-needle sampling to obtain cytological samples is a well-established technique. However, the application of suction during sampling is controversial. Evidence from the human literature and one previous veterinary study suggest that non-aspiration may be superior for a number of organs. This prospective study compared the quality and diagnostic value of cytological samples from canine livers obtained by fine-needle aspiration (FNA) and non-aspiration (FN-NA) techniques. A total of 119 dogs that required ultrasound-guided FNA of the liver as part of their clinical investigation were recruited and randomly assigned to either FNA (n=54) or FN-NA (n=65) sampling groups. Specimens were reviewed by external cytopathologists masked to the technique used. Cytological reports were reviewed for their overall diagnostic value, cellularity, cell preservation and haemodilution.Overall, 88.2% (95% confidence intervals [CI], 82.4–94.0) of samples were diagnostic. There was a significant difference, as demonstrated by Chi-squared statistical analysis, in the prevalence of diagnostic samples between the FNA (81.5%; 95% CI, 71.1–91.8) and FN-NA groups (93.9%; 95% CI, 88.0–99.7; P=0.037). Non-diagnostic samples were significantly associated with lower cellularity, poorer cell preservation and more severe haemodilution (P<0.001 for each). However, there were no significant differences in the frequency of these specific variables between the FNA and FN-NA groups. In this study, fine-needle non-aspiration was superior to an aspiration technique for sampling the canine liver, as it resulted in higher rates of diagnostic cytology samples, with greater cellularity, less haemodilution and better cytological preservation.

Effects of Cardiopulmonary Bypass Circuit Shortening on Transfusion Reduction: A Retrospective Cohort Study in the Cardiac Surgery Patients

Background: Hemodilution anemia, due to the use of crystalloid liquids during the preparation of cardiopulmonary bypass (CPB) circuits, results in the increased number of RBC, which may lead to hemolysis, acute pulmonary injury, allergic reactions, metabolic and coagulative abnormalities, volume overload, alloimmunization, immunosuppression, graft versus host reaction, and a remarkable increase in hospitalization costs. Objectives: The present study aimed to evaluate the effects of shortened cardiopulmonary bypass circuits on the blood salvage process in patients undergoing cardiac surgery with cardiopulmonary bypass and determine the cutoff BSA value for effectiveness. Methods: A retrospective cohort study was performed in a private hospital, Ankara, Turkey, between January 2011 and November 2015 to assess 235 patients having a CPB with shortened circuits. The control group comprised 240 patients who underwent cardiac surgery utilizing a standard extracorporeal circulation circuit at our institution. In the case group, to achieve a low-priming volume, the CPB circuit was shortened and CPB console was positioned as close as possible to the operative field. The arterial line (3/8”) and the venous line (1/2) were 80 cm and 90 cm, respectively, shorter in the case group than in the control group. Patient data were collected by retrospective medical chart review. Results: Intraoperative red blood cell (RBC) transfusion amount was 465 ± 141.5 mL in the case group and 722.5 ± 285.4 mL in the control group (P < 0.001). Postoperative RBC transfusion was 418.7 ± 198.1 mL in the case group and 628.7 ± 452.3 mL in the control group (P < 0.001). The total amount of RBC transfusion was 742.4 ± 228.7 mL in the case group and 1012.3 ± 625.5 mL in the control group (P < 0.001). ROC analysis showed that shortening the CPB circuits was effective in patients with a BSA of < 1.67 (AUC = 0.84; P < 0.001) Conclusions: Shortening of the CPB circuit could be helpful to avoid severe hemodilution and to reduce RBC use in small adult patients (with BSA < 1.67) undergoing cardiac surgery with cardiopulmonary bypass.

Prompt rise in urinary ammonium excretion suffices to mitigate metabolic acidosis in an experimental animal model of severe normovolemic hemodilution.

Recently, we have established a model of severe stepwise normovolemic hemodilution to a hematocrit of 10 % in rats employing three different colloidal volume replacement solutions (Voluven, Volulyte and Gelafundin) that are routinely used in clinical practice at present. We did not see severe dilutional acidosis as to be expected, but a decline in urinary pH. We here looked on further mechanisms of renal acid excretion during normovolemic hemodilution. Bicarbonate, which had been removed during normovolemic hemodilution, was calculated with the help of the Henderson-Hasselbalch equation. The urinary amount of ammonium as well as phosphate was determined in residual probes. The absolute amount of free protons in urine was obtained from the pH of the respective samples. The amount of protons generated during normovolemic hemodilution was approximately 0.6 mmol. During experimental time (5.5 h), distinct urinary ammonium excretion occurred (Voluven 0.52 mmol, Volulyte 0.39 mmol and Gelafundin 0.77 mmol). Proton excretion via the phosphate buffer constituted 0.04 mmol in every experimental group. Excretion of free protons was in the range of 10(-6) mmol. The present data prove that the prompt rise in urinary ammonium excretion is also valid for acute metabolic acidosis originating from severe normovolemic hemodilution.

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

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. Retrospective cohort study. University research hospital. The study comprised 793 cardiac surgery patients. None. 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%). SH on CPB is associated with hypocoagulation, bleeding, and thrombosis-associated worse outcomes.

Ideal Hematocrit to Minimize Renal Injury on Cardiopulmonary Bypass.

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. 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. 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). 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.

Effects of different durations of severe acute hypervolemic hemodilution on acute lung injury in rabbits

Objective To evaluate the effects of different durations of severe acute hypervolemic hemodilution (AHH) on acute lung injury in rabbits. Methods Thirty-six healthy adult rabbits of both sexes, weighing 2.7-3.1 kg, were randomly divided into 2 groups (n=18 each) using a random number table: control group (C group) and AHH group.AHH was performed with 6% hydroxyethyl starch 130/0.4 until the target hematocrit of 20% was achieved in group AHH.Immediately before AHH (T0), and at 1, 2 and 4 h after AHH (T1-3), blood samples were taken from the right femoral artery for blood gas analysis.The oxygenation index was calculated.The occurrence of acute lung injury (oxygenation index ≤ 300 mmHg) was recorded.After blood samples were collected at T1-3, 6 rabbits in each group were sacrificed, and lungs were removed for determination of wet/dry lung weight ratio (W/D ratio) and aquaporin-1 (AQP-1) expression (by immuno-histochemistry). Results In group AHH, 1 rabbit developed acute lung injury at 1-2 h after AHH, and 4 rabbits developed acute lung injury at 2-4 h after AHH.Compared with group C, W/D ratio was significantly increased at T1-3, and the expression of AQP-1 was down-regulated at T2, 3 in group AHH (P<0.05 or 0.01). Conclusion Severe AHH performed with 6% hydroxyethyl starch 130/0.4 with the target hematocrit reduced to 20% and the duration > 1 h induces acute lung injury in rabbits. Key words: Hemodilution; Respiratory distress syndrome, adult

Recombinant Factor VIIa Reduces Bleeding after Blunt Liver Injury in a Pig Model of Dilutional Coagulopathy under Severe Hypothermia.

BackgroundRecombinant factor VIIa (rFVIIa) is registered for use in haemophilia with inhibitors and other rare bleeding disorders, but has also been used in various other clinical conditions to terminate life-threatening bleeding. Underlying conditions (e.g. coagulopathy) and dosing may affect treatment efficacy. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury.MethodsA grade III blunt liver injury was induced in 28 pigs after 70% haemodilution and cooling to 32.6–33.4°C. Ten minutes after trauma, animals randomly received placebo or 90, 180 or 360 μg/kg rFVIIa. Global coagulation parameters, thromboelastometry (TEM) and plasma thrombin generation (TG) were determined at different time points during the observation period of 120 minutes.ResultsTotal blood loss was significantly lower following 90 μg/kg rFVIIa (1206 [1138–1470] mL) relative to placebo (2677 [2337–3068] mL; p<0.05), with no increased effect with higher dose levels of rFVIIa. Following trauma and haemodilution, coagulation was impaired relative to baseline in both TEM and TG analysis. At 60 and 120 minutes after trauma, TEM variables improved in the rFVIIa-treated animals compared with the placebo group. Similarly, rFVIIa improved coagulation kinetics in TG. As was observed with blood loss, no significant effect between different rFVIIa dose levels was found in TEM or TG. Macro- and microscopic post-mortem examination did not reveal any signs of thromboembolic events.ConclusionEarly administration of 90 μg/kg rFVIIa reduced blood loss in pigs undergoing blunt liver injury even after severe haemodilution and hypothermia, with no further effect of higher dose levels. Coagulation assays showed impaired coagulation in coagulopathic animals, with a dose-independent improvement in animals treated with rFVIIa.

Acute Kidney Injury and Hemodilution During Cardiopulmonary Bypass: A Changing Scenario

Severe hemodilution during cardiopulmonary bypass (CPB) is a risk factor for acute kidney injury (AKI) after heart operations. Many improvements to CPB technology have been proposed during the past decade to limit the hemodilution-related AKI risk. The present study is a retrospective analysis of the relationship between hemodilution during CPB and AKI in cardiac operations in the setting of different interventions applied over 14 years. We retrospectively analyzed 16,790 consecutive patients undergoing heart operations from 2000 to 2013. Various risk factors for AKI were collected and analyzed, together with a number of interventions as possible modifiers of the relationship between a nadir hematocrit (HCT) value during CPB and AKI. The relationship between the nadir HCT value during CPB and AKI was confirmed in a multivariable analysis, with the relative risk of AKI increasing by 7% per percentage point of decrease of the nadir HCT value during CPB. The relative risk of AKI decreased by 8% per year of observation (p = 0.001) despite a significantly increased risk of AKI (p = 0.001). A sensitivity analysis based on differences before and after different interventions demonstrated a beneficial effect of the application of goal-directed perfusion (aimed at preserving oxygen delivery during CPB), with a reduction in the AKI rate from 5.8% to 3.1% (p = 0.001). A policy restricting angiographic examination on the day of operation was also useful (reduction of AKI rate from 4.8% to 3.7%; p = 0.029). A bundle of interventions mainly aimed at limiting the renal impact of hemodilution during CPB is effective in reducing the AKI rate.

Association of Gender and Lowest Hematocrit on Cardiopulmonary Bypass With Acute Kidney Injury and Operative Mortality in Patients Undergoing Cardiac Surgery

Nadir hematocrit on cardiopulmonary bypass (CPB) is a known risk factor for worse outcomes after cardiac surgery. Whether women, because of lower nadir hematocrit on CPB, are more prone to worse outcomes than men after cardiac surgery remains unknown. We evaluated 13,734 patients (31.3% women) undergoing cardiac surgery (6/1/2001 to 06/30/2011) to study the association of hematocrit on CPB and gender with postoperative acute kidney injury (AKI) stage 2-3 (increase in creatinine at least twice the baseline), and operative mortality. Women were older (68 ± 12 vs 65 ± 12 years, p < 0.001), with more comorbidities. Baseline (37.4% ± 4.4% vs 39.8% ± 4.6%, p < 0.001) and nadir (24.5% ± 3.5% vs 27.4% ± 3.6%, p < 0.001) hematocrit were lower, whereas the hematocrit drop on CPB (baseline and nadir) was greater in women (12.9% ± 4.35 vs 12.4% ± 4.2%, p < 0.001). Observed AKI stage 2-3 and mortality rates were significantly higher in women than in men (5.8% vs 4.9%, p = 0.025 and 4.3% vs 3.4%, p = 0.009, respectively). While nadir hematocrit was inversely related to AKI stage 2-3 and death in both genders, the subgroup of patients with severe hemodilution (nadir hematocrit ≤ 22%) demonstrated a nonsignificant higher rate of AKI stage 2-3 in men (9.2% vs 7.8%) and a significant higher mortality in men (11% vs 7.6%) compared with women. Both men and women undergoing cardiac surgery on CPB were prone to the deleterious effects of hemodilution on renal function and death. Yet, despite greater hemodilution, women had a lower relative risk of AKI and death than men at lower nadir hematocrit values on CPB suggesting better tolerance to hemodilution in women.

Vasoactive hemoglobin solution improves survival in hemodilution followed by hemorrhagic shock*

To compare survival after exchange transfusion followed by hemorrhage using: 1) the vasoactive, oxygen-carrying, bovine hemoglobin-based blood substitute Oxyglobin (Biopure, 12.9 g hemoglobin/dL); and 2) the hydroxyethyl starch plasma expander Hextend (high molecular weight and low degree of substitution, 6%). Comparison between treatments. Laboratory. Awake hamster chamber window model. Fifty percent blood volume exchange transfusion followed by a 60% hemorrhage over 1 hr, followed by 1 hr of observation. Measurement of blood gases, mean arterial blood pressure, functional capillary density, arteriolar and venular diameter, and Po2 tension distribution. Survival with Oxyglobin was 100% and only 50% for the Hextend group. Vasoconstriction was evident in the microcirculation. Mean arterial pressure was higher in the Oxyglobin group. Functional capillary density was significantly reduced, although to a lesser extent by Oxyglobin. There was no difference in microvascular Po2 distribution after 1 hr of shock between groups. Higher mean arterial pressure during the initial stages of hemorrhage could be due to vasoconstriction in the Oxyglobin group as compared to the Hextend group. It is concluded that the pressor effect due to a vasoactive oxygen carrier may be beneficial in maintaining perfusion in conditions of severe hemodilution followed by hypovolemia.

Invited Commentary

Stroke after cardiac surgery is a devastating complication that, depending on the definition, still affects 2% to 5% of the patient population. Despite many improvements in the technical aspects of cardiac operations, and probably due to the increasing rate of elderly patients, postoperative stroke rate does not seem to decline. Historically, the pathogenetic mechanisms leading to permanent stroke or other temporary minor focal injuries have been attributed to two main different fields: (1) microembolic or macroembolic events; and (2) cerebral perfusion defects, mostly pertaining to cardiopulmonary bypass (low perfusion pressure, inadequate coupling of pump flow and temperature, severe hemodilution).

Fibrinogen concentrate for management of bleeding

Fibrinogen concentrate for management of bleeding

Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model

Replacement of fibrinogen is presumably the key step in managing dilutional coagulopathy. We performed an in vitro study hypothesizing that there is a minimal fibrinogen concentration in diluted whole blood above which the rate of clot formation approaches normal. Blood samples from six healthy volunteers were diluted 1:5 v/v with saline keeping haematocrit at 24% using red cell concentrates. We measured coagulation factors and thrombin generation in plasma at baseline and after dilution. Thromboelastometry was used to evaluate (i) speed and quality of clot formation in diluted samples supplemented with fibrinogen 50-300 mg dl(-1) and (ii) clot resistance to fibrinolysis. Diluted and undiluted samples with no added fibrinogen served as controls. Coagulation parameters and platelets were reduced by 74-85% after dilution. Peak thrombin generation was reduced by 56%. Adding fibrinogen led to a concentration-dependent improvement of all thromboelastometric parameters. The half maximal effective concentration (EC50) for fibrinogen replacement in haemodiluted blood was calculated to be 125 mg dl(-1). Adding tissue plasminogen activator, 0.15 microg ml(-1), led to a decrease of clot firmness and lysis time. The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl(-1) as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.

Optimal Perfusion During Cardiopulmonary Bypass: An Evidence-Based Approach

In this review, we summarize the best available evidence to guide the conduct of adult cardiopulmonary bypass (CPB) to achieve "optimal" perfusion. At the present time, there is considerable controversy relating to appropriate management of physiologic variables during CPB. Low-risk patients tolerate mean arterial blood pressures of 50-60 mm Hg without apparent complications, although limited data suggest that higher-risk patients may benefit from mean arterial blood pressures >70 mm Hg. The optimal hematocrit on CPB has not been defined, with large data-based investigations demonstrating that both severe hemodilution and transfusion of packed red blood cells increase the risk of adverse postoperative outcomes. Oxygen delivery is determined by the pump flow rate and the arterial oxygen content and organ injury may be prevented during more severe hemodilutional anemia by increasing pump flow rates. Furthermore, the optimal temperature during CPB likely varies with physiologic goals, and recent data suggest that aggressive rewarming practices may contribute to neurologic injury. The design of components of the CPB circuit may also influence tissue perfusion and outcomes. Although there are theoretical advantages to centrifugal blood pumps over roller pumps, it has been difficult to demonstrate that the use of centrifugal pumps improves clinical outcomes. Heparin coating of the CPB circuit may attenuate inflammatory and coagulation pathways, but has not been clearly demonstrated to reduce major morbidity and mortality. Similarly, no distinct clinical benefits have been observed when open venous reservoirs have been compared to closed systems. In conclusion, there are currently limited data upon which to confidently make strong recommendations regarding how to conduct optimal CPB. There is a critical need for randomized trials assessing clinically significant outcomes, particularly in high-risk patients.

Behaviour at eight years in children with surgically corrected transposition: The Boston Circulatory Arrest Trial

Uncertainty exists regarding the degree to which infants with congenitally malformed hearts are at risk of behavioural disorders in childhood. Data was collected as part of a randomized clinical trial involving 155 children with surgically corrected transposition (concordant atrioventricular and ventriculo-arterial connections or alignments). As infants, they underwent the arterial switch operation, involving deep hypothermia with predominantly total circulatory arrest or predominantly low-flow continuous cardiopulmonary bypass as the method of providing support to the vital organs. Parents completed the Child Behavior Checklist when the patients were aged 4 and 8 years, and the Connors' Parent Rating Scale at the age of 8 years. When the children were aged 8, teachers completed the Teacher's Report Form and the Connors' Teacher Rating Scale. In the cohort as a whole, the frequencies of behavioural problems identified by both parents and teachers were elevated, particularly on the scales for competence of the Child Behavior Checklist, and the Adaptive scales of the Teacher's Report Form. Approximately 1 in 5 patients had scores for Total Problem Behavior in the range of clinical concern on both the Child Behavior Checklist and the Teacher's Report Form. Few differences were found, however, according to the method of operative treatment. Postoperative seizures were associated with social and attention problems. Children experiencing academic problems at the age of 8 showed a larger increase in behavioural problems between the ages of 4 and 8 than did children making adequate academic progress. Children with congenitally malformed hearts who underwent reparative surgery in infancy using a strategy of severe haemodilution and alpha stat are at increased risk of behavioural problems in middle childhood.