Validating the Physiologic Model HumMod as a Substitute for Clinical Trials Involving Acute Normovolemic Hemodilution.

BACKGROUND: Blood conservation strategies and transfusion guidelines remain a heavily debated clinical topic. Previous investigational trials have shown that acute isovolemic hemodilution does not limit adequate oxygen delivery; however, a true critical hemoglobin level has never been investigated or defined due to safety concerns for human volunteers. Validated physiologic modeling may be useful to investigate hemodilution at critical hemoglobin levels without the ethical or safety hazards of clinical trials. Our hypothesis is that HumMod, an integrative physiological model, can replicate the cardiovascular and metabolic findings of previous clinical studies of acute isovolemic hemodilution and use coronary blood flow and coronary oxygen delivery in extreme hemodilution to predict a safety threshold. METHODS: By varying cardiovascular and sizing parameters, unique individuals were generated to simulate a population using HumMod, an integrative mathematical model of human physiology. Hemodilution was performed by simultaneously hemorrhaging 500 mL aliquots of blood while infusing equal volumes of hetastarch, 5% albumin balanced salt solution, or triple volumes of lactated Ringer's solution over 10 minutes. Five hemodilution protocols reported over 3 studies were directly replicated with HumMod to compare and validate essential cardiovascular and metabolic responses to hemodilution in moderately healthy, awake adults. Cardiovascular parameters, mental status, arterial and mixed venous oxygen content, and oxyhemoglobin saturation were recorded after the removal of each aliquot. The outputs of this simulation were considered independent variables and were stratified by hemoglobin concentration at the time of measurement to assess hemoglobin as an independent predictor of hemodynamic and metabolic behavior. RESULTS: The published reports exhibited discrepancies: Weiskopf saw increased heart rate and cardiac index, while Jones and Ickx saw no change in these variables. In HumMod, arterial pressure was maintained during moderate hemodilution due to decreases in peripheral resistance opposing increases in cardiac index. HumMod showed preserved ventilation through moderate hemodilution, compensated for by an increased oxygen extraction similar to the studies of Jones and Ickx. The simulation results qualitatively followed the clinical studies, but there were statistical differences. In more extreme hemodilution, HumMod had a lesser increase in cardiac index, which led to deficiencies in oxygen delivery and low venous saturation. In the simulations, coronary blood flow and oxygen delivery increase up to a critical hemoglobin threshold of 55-75 g/L in HumMod. In this range, coronary blood flow and oxygen delivery fell, leading to cardiac injury. The allowable amount of hemodilution before reaching the critical point is most closely correlated with nonmuscle mass (r = 0.69) and resting cardiac output (r = 0.67). CONCLUSIONS: There were significant statistical differences in the model population and the clinical populations, but overall, the model responses lay within the clinical findings. This suggests our model is an effective replication of hemodilution in conscious, healthy adults. A critical hemoglobin range of 5.5-7.5 g/L was predicted and found to be highly correlated with nonmuscle mass and resting cardiac output.

Improvements in blood transfusion management: cross-sectional data analysis from nine hospitals in Zhejiang, China.

BACKGROUND: Since 2008, updated perioperative blood management (PoBM) guidelines have been implemented in Zhejiang, China. These guidelines ensure that the limited blood resources meet increasing clinical needs and patient safety requirements. We assessed the effects of implementing updated PoBM guidelines in hospitals in Zhejiang, China. METHODS: We performed a retrospective multicenter study that included adult patients who received blood transfusions during surgical care in the years 2007 and 2011. The volume of allogeneic red blood cells or autologous blood transfusions (cell salvage and acute normovolemic hemodilution [ANH]) for each case was recorded. The rates of performing appropriate pre-transfusion assessments during and after surgery were calculated and compared between the 2 years. RESULTS: We reviewed 270,421 cases from nine hospitals. A total of 15,739 patients received blood transfusions during the perioperative period. The rates of intraoperative allogeneic transfusion (74.8% vs. 49.9%, p <  0.001) and postoperative transfusion (51.9% vs. 44.2%, p <  0.001) both decreased from 2007 to 2011; the rates of appropriate assessment increased significantly during (63.0% vs. 78.0%, p <  0.001) and after surgery (70.6% vs. 78.4%, p <  0.001). The number of patients who received cell salvage or ANH was higher in 2011 (27.6% cell salvage; 9.3% ANH) than in 2007 (6.3% cell salvage; 0.1% ANH). CONCLUSION: Continuing education and implementation of updated PoBM guidelines resulted in significant improvements in the quality of blood transfusion management in hospitals in Zhejiang, China.

Isovolemic hemodilution-red cell exchange for prevention of cerebrovascular accident in sickle cell anemia: the standard operating procedure.

Red blood cell exchange is an accepted superior therapy to simple chronic transfusion, due to minimal risk of iron overload, for secondary prevention of cerebrovascular accidents in selected patients with sickle cell anemia. Recently, we described our experience of Isovolemic Hemodilution-Red Blood Cell Exchange (IHD-RBCx), a two-step modification of the conventional RBCx with several advantages, including cost reduction. We are describing our standard operating procedure for IHD-RBCx with COBE Spectra apheresis system to make it widely available to the apheresis centers interested in implementing this procedure.

Venous drainage--gravity or assisted?

Since the early start of cardiopulmonary bypass, vascular access has been recognized as a main variable for obtaining optimal blood flow during cardiopulmonary bypass. In particular, venous drainage can limit the maximum flow as the wide, low-resistance, collapsible veins are connected with smaller stiff cannulas and tubing. Due to the introduction of long venous cannulas for minimally invasive cardiac surgery and the desire to limit hemodilution during cardiopulmonary bypass, more and more centers have started using assisted venous drainage techniques. This article gives an overview of these techniques, with their respective advantages and disadvantages.

Fibrinogen estimates are influenced by methods of measurement and hemodilution with colloid plasma expanders.

BACKGROUND: Measurement of plasma fibrinogen is often required in critically ill patients or massively bleeding patients being resuscitated with colloid plasma expander. This study aimed at evaluating different assays of plasma fibrinogen after in vitro dilution with commonly used plasma expanders and challenged the hypothesis that levels of fibrinogen are estimated significantly higher in plasma diluted with colloid plasma expander compared with isotonic saline. STUDY DESIGN AND METHODS: Fibrinogen measurements were established in plasma samples each diluted in vitro to 30 or 50% with isotonic saline, hydroxyethyl starch (HES) 130/0.4, and human albumin. Fibrinogen levels were assessed using an antigen determination, three photo-optical Clauss methods, one mechanical Clauss method, a prothrombin-derived method, and viscoelastic measurement through thromboelastometry. RESULTS: Measurement of fibrinogen levels was significantly different when performed on alternate analytical platforms. By 30 and 50% dilution with HES 130/0.4 coagulation analyzers using the photo-optical Clauss methods significantly overestimated levels of fibrinogen. Dilution with human albumin did not affect fibrinogen levels except from one analyzer by 50% dilution level. Viscoelastic measurement of fibrin polymerization was reduced at both dilution levels and appeared to reflect the impairment of fibrin polymerization induced by HES 130/0.4 and to a lesser extent human albumin. CONCLUSION: This study demonstrated that different automated coagulation analyzers revealed significantly different levels of fibrinogen. The presence of colloid plasma expander gave rise to erroneous high levels of fibrinogen returned from some coagulation analyzers employing the method of Clauss.

Parsimonious blood use and lower transfusion triggers: What is the evidence?

Evidence supports a parsimonious approach to blood use for managing anemia, contrasting with the long-standing practice of blood transfusion targeting arbitrary hemoglobin levels. Hemodilution studies have demonstrated that humans can tolerate anemia. The cumulative data have confirmed and validated the safety of a conservative approach to transfusion. This has translated into formal national guidelines for blood transfusion as well as patient safety and quality markers supporting blood management stewardship to minimize unnecessary use of blood products.

Modern concepts of autologous haemotherapy.

The increasing current perception that the safety of allogeneic blood transfusion has dramatically been improved during the last decade is challenging autologous haemotherapy methods. In addition, growing concern about the unfavourable cost-effectiveness of most autologous haemotherapy methods requires a refinement of the application of these measures to well defined circumstances. In contrast, newly emerging transfusion-transmissible infections or periods of blood shortage might revive interest in these blood sparing techniques. Preoperative autologous blood donation still plays a significant role in settings with high individual benefit for the patient, high transfusion probabilities and when all opportunities of cost minimization can be applied. Preoperative plasmapheresis is considered to be a sensible adjunct if intraoperative retransfusion of salvaged and washed red cells is planned. Acute normovolaemic haemodilution is valuable when the patient's tolerability of the haemodilution and the expected blood loss are carefully examined beforehand. Intra- or postoperative salvage of wound blood can also be regarded as useful measures to prevent allogeneic transfusions as long as the specific advantages and disadvantages of the different methods are taken into account. Finally, alternative and supplemental measures such as iron or erythropoietin administration should always be considered in order to optimize the efficacy and effectiveness of autologous haemotherapy methods. The goal of a "bloodless medicine" might not be reached but is supposed to be approached closely with an integrated concept exploiting all measures available. However, in times of restricted health care resources, regular sound cost-effectiveness analyses, taking the availability and the current safety profile of allogeneic blood products into account, are always warranted and needed.

Low molecular weight hydroxyethyl starch 6% compared to albumin 4% during intentional hemodilution.

Intentional normovolemic hemodilution was chosen as the model to compare a 6% low molecular weight hydroxyethyl starch (LMW HES) to 4% albumin. The study ran over the plasma exchange period for 24 h. Nine patients, scheduled for abdominal aortic surgery, were included in each group. After basal measurements, blood was withdrawn and simultaneously replaced by either 4% albumin (Group 1) or 6% LMW HES (Group 2) to achieve a final hematocrit of approximately 30%. Hemodynamic blood oxygen gas and hormonal plasma levels were determined before hemodilution then at 30 min, 1, 2, 3, and 24 h after the end of hemodilution. Basal value for total blood volume was 4377 +/- 162 ml in group 1 and 4138 +/- 315 ml in group 2. As in both groups the decrease in blood cell volume was exactly compensated by the increase in plasma volume, no significant change in total blood volume (respectively 4432 +/- 159 and 4305 +/- 267 ml) was observed. Throughout the study, in both groups, no significant change in mean arterial and right atrial pressures was observed. In group 2 (LMW HES), a significant increase of pulmonary capillary wedge pressure was noted 120 min after hemodilution. After hemodilution, despite a significant decrease in arterial oxygen O2 content, systemic oxygen transport did not significantly vary until 24 h in relation to the increased cardiac index. An increase in O2 extraction was observed after the exchange but no further increase was observed until the 24 h. No significant changes either in global O2 consumption or in lactate concentration were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertensive, hypervolemic, hemodilutional therapy for aneurysmal subarachnoid hemorrhage. Is it efficacious? Yes.

Vasospasm is an important contributor to death and disability after aneurysmal SAH. CBF is decreased after SAH and correlates inversely with the severity of the clinical grade. It is necessary to avoid hypotension and hypovolemia, which can exacerbate an already reduced CBF, resulting in critically low perfusion. There have been no human, prospective, randomized trials of HHH therapy. This is attributable, perhaps, to the fact that such trials are difficult to blind. Nevertheless, there is strong evidence that HHH therapy can reverse the delayed onset of profound neurologic deficits by restoring blood flow to ischemic regions, and its prophylactic use can reduce the incidence and severity of DID.

Hypertensive, hypervolemic, hemodilutional therapy for aneurysmal subarachnoid hemorrhage. Is it efficacious? No.

Many neurosurgeons routinely use hypertensive, hypervolemic, hemodilutional, or hyperdynamic therapy (HT) in some form to prevent or to treat vasospasm. Despite the widespread use of this therapy during the past 20 years, however, there are no randomized, prospective, controlled clinical studies demonstrating that HT improves the short- or long-term neurologic outcome or survival after subarachnoid hemorrhage. Guidelines need to be developed to standardize the clinical application of HT, and well-controlled, prospective, randomized clinical trials must be conducted before HT can become an accepted treatment for vasospasm.

Intravenous fluid therapy in neurologic injury.

Cerebral autoregulation and the blood-brain barrier are two important mechanisms that attempt to preserve brain homeostasis. The function of either may be disrupted by injury. When autoregulation is impaired, blood pressure and hematocrit determine cerebral oxygen delivery. Injury to the blood-brain barrier impairs brain volume regulation and may contribute to cerebral edema. The choice of intravenous fluid influences cerebral blood flow, cerebral oxygen delivery, brain metabolism, and brain volume.

Efficacy of autotransfusion in spine surgery: comparison of autotransfusion alone and with hemodilution and apheresis.

STUDY DESIGN: Two prospective groups of patients received intraoperative autologous transfusion during reconstructive spine surgery. Before intraoperative autologous transfusion, one group underwent normovolemic hemodilution and apheresis of blood components in the operating room while being prepared for surgery. The allogeneic blood products needed for transfusion by each group were studied and compared with those of a retrospective group of patients receiving conventional transfusion therapy. OBJECTIVES: To determine if a combination of intraoperative autologous transfusion and hemodilution and apheresis decreases reliance on allogeneic blood products and increases autologous transfusions. SUMMARY OF BACKGROUND DATA: Transfusion rates of allogeneic red blood cells, which were unchanged by intraoperative autologous transfusion alone, were lowered when treatment included transfusion of these cells and preoperative autologous deposit. However, donor exposures from transfusions of allogeneic platelets and fresh frozen plasma have not been addressed. METHOD: Preoperative hemodilution and apheresis of autologous red blood cells, fresh plasma, and platelets, performed during induction of anesthesia for spine surgery was followed by intraoperative autologous transfusion using the same supplies. Intra- and postoperative transfusion of blood products to each group were evaluated and compared; allogeneic transfusions were given to a retrospective cohort of patients who received conventional transfusion therapy. RESULTS: Hemodilution and apheresis followed by intraoperative autologous transfusion reduced exposures to individual blood donor products resulting in fewer transfusions and in transfusion of significantly fewer blood products. Intraoperative autologous transfusion alone decreased the number of red blood cells transfused, but required the same donor exposures for fresh frozen plasma and platelet support as the cohort of patients who received conventional transfusion therapy. CONCLUSIONS: A combination of hemodilution and apheresis and intraoperative autologous transfusion significantly decreased transfusion of allogeneic blood products and reliance on preoperative autologous deposit. Autologous transfusion of all blood products was significantly increased.

Intraoperative blood salvage (IOBS) in cardiac and vascular surgery.

The extensive application of IOBS has permitted a great reduction in the use of homoglous transfusion which presently represents the largest field of application of autologous systems. In cardiac and vascular surgery, IOBS is particularly useful to the goal of preventing the transmission of viral disorders and other adverse effects related to homologous transfusions. The apparatuses for IOBS may also be used to perform hemodilution and sequestration of a desired amount of platelet rich plasma. The appropriate usage of drugs in perioperative period and the promotion of hemostasis with IOBS are important costituents for the correct transfusional management of the patient. The feasibility and safety of IOBS is known and in expert hands it is an optimal method for the transfusional treatment of surgical patients.

From low hematocrit physiology to isovolemic hemodilution.

The aim of this study, starting from some concepts of physiology, was to deal with the ever growing question of intentional anemia. Physiology suitably expresses the linear relationship between hematocrit and blood fluidity, and at the same time explains how viscosity and aggregability are important co-factors in the circulation, in disease and in thromboembolic complications. The need to understand how a low hematocrit level, compared to the volemia, is a fundamental requirement in surgery, and even more so in surgery with a high risk of embolism, like orthopedic traumatology surgery. Normovolemic hemodilution was analyzed both for the risks it involves and for how much it sticks to the changes induced by a similar situation on the various organs and apparatus. The authors, based on their experience in the field of anesthesiology, propose an operating schedule to safely perform intentional normovolemic hemodilution, describing the preoperative, intraoperative and finally the postoperative period. In conclusion, the authors advocate a wider use of this technique, confirming its safety in relation to volemia.

Anaesthesia and autologous transfusion.

The anaesthesiologist plays a central role in co-ordinating the combined application of the various blood saving techniques. In fact, to carry out transfusion therapy correctly, the anaesthesiologist must plan the right number of units of predeposit blood during the first examination, estimate the salvage of intra and post operative blood loss and spread the infusion of the units over the first three days in order to keep the patient in a state of haemodilution. From January 1992 to June 1994 in the department of anaesthesia and the intensive care unit, 980 patients were treated for total joint replacement: 714 total hips (7 after removal of plates and screws) 145 revisions, and 121 total knee prostheses. Basal Hb was 13.4 +/- 1.4 g/dl (range 6.7-17.9 g/dl). Homologous transfusions were carried out in 6.3% of these patients. The need to use homologous transfusions was negatively influenced by female sex, coronary heart disease (p = 0.005), length of surgery and type of antithromboembolic prophylaxis (indobufen has a significantly low incidence-p = 0.0001--compared to calcium heparin or low molecular weight heparin).

Impact of extracorporeal circuit prime volume reduction on whole blood sequestration during acute normovolemic hemodilution for adult cardiac surgery patients.

Acute normovolemic hemodilution (ANH) is a blood-conservation method in which whole blood (WB(ANH)) is sequestered into blood collection bags before the commencement of surgery. However, for cardiac surgery, extracorporeal circuit (ECC) priming techniques limit the amount of blood that may collected prior to the actual initiation of cardiopulmonary bypass (CPB). In this study, computational modeling was used to examine the effect of reducing extracorporeal "pump" prime volume (PPV) on WB(ANH) prior to the CPB. Increments of estimated blood volume (EBV), precardiopulmonary bypass hemoglobin concentration [Hb(Pre-CPB)], and PPV volume were manipulated to assess effects on predicted hemoglobin concentration during cardiopulmonary bypass [Hb(CPB)]. Similarly, increments of EBV and preanesthetic hemoglobin concentration [Hb(Pre-Anes)] were manipulated to examine the change in WB(ANH) volume. The impact of PPV reduction on the minimum acceptable precardiopulmonary bypass hemoglobin concentration [Hb(Pre-CPB-MA)] was then measured by computing PPV, EBV, and the minimum acceptable cardiopulmonary bypass hemoglobin [Hb(CPB-MA)]. Finally, by manipulating EBV and target hemoglobin concentration [Hb(Target)], the change in [Hb(Pre-CPB)] produced by PPV reduction was used to quantify the effect on WB(ANH) volume. The net increase in the [Hb(CPB)] produced by PPV reduction is inversely proportional to EBV. Higher [Hb(Pre-Anes)] or lower [Hb(Target)] facilitates sequestration of larger WB(ANH) volume. Although PPV and [Hb(Pre-CPB-MA)] bear a direct relationship, as EBV decreases, proportionally greater increases in [Hb(Pre-CPB-MA)] occur. The impact of PPV reduction on precardiopulmonary bypass hemoglobin concentration [Hb(Pre-CPB)] is reflected by the "excess hemoglobin" over the minimum hemoglobin threshold (designated as 7 g/dL in this study). For each 100-mL decrement in PPV, "excess hemoglobin" increases from 1% (EBV = 8000 mL) to 2% (EBV = 4000 mL). In turn, increases in "excess hemoglobin" are associated with expansion of WB(ANH) volume. In conclusion, sequential PPV reduction from 2000 mL increases the volume of WB(ANH) that potentially may be sequestered prior to initiation of CPB. Therefore, the combination of PPV reduction with ANH may represent a useful blood conservation approach in adult patients undergoing cardiac surgery with CPB.

Anemia and transfusion in critically ill pediatric patients: a review of etiology, management, and outcomes.

This article describes the incidence and etiology of anemia in critically ill children. In addition, the article details the pathophysiology and clinical ramifications of anemia in this population. The use of transfused packed red blood cells as a therapy for anemia in critically ill patients is also discussed, including the indications for and complications associated with this practice as well as potential reasons for these complications. Finally, the article lists some therapeutic practices that may lessen the risks associated with transfusion, and briefly discusses the use of blood substitutes.