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Background. Utilization of an individual patient's tolerance of anaemia is a cornerstone of any restrictive transfusion policy. Whether the use of neuromuscular block (NMB) has an effect on anaemia tolerance has not been investigated. Methods. Fourteen anaesthetized and mechanically ventilated pigs were randomized to receive either rocuronium bromide 1% (Roc-group, n=7, 0.378 ml kg-1 bolus injection, 0.1 ml kg-1 min-1 continuous infusion) or the same volume of normal saline (Sal-group, n=7). Acute normovolaemic anaemia was induced by exchange of whole blood for a 6% HES-solution (130/0.4) until a sudden decrease in total body O2 consumption (VO2) indicated a critical limitation of O2 delivery to the tissues. The Hb concentration quantified at this critical time point (HbCRIT) was defined as the primary endpoint of the protocol. Secondary endpoints were parameters of central haemodynamics, O2 transport, and tissue oxygenation. Results. HbCRIT was significantly lower in the Roc-group [2.4 (0.5) vs 3.2 (0.7) g dl-1] reflecting increased tolerance of anaemia. NMB with rocuronium bromide reduced skeletal muscle O2 consumption (mVO2) and the total body O2 extraction ratio. As cardiac index increased, body O2 consumption (VO2) decreased marginally in the Roc-group [change of VO2 relative to baseline (ΔVO2) -1.7 (0.8)% vs 3.2 (1.9)% in the Sal-group, P<0.05]. Conclusions. NMB with rocuronium bromide increases the tolerance of acute normovolaemic anaemia. The underlying mechanism probably involves a reduction in skeletal muscle O2 consumption. During acellular treatment of acute blood loss, NMB might play an adjuvant role, particularly in situations where profound normovolaemic anaemia has to be tolerated, for example, bridging an acute blood loss until compatible blood products become available for transfusion. [ABSTRACT FROM AUTHOR]

Background: Jehovah's Witness (JW) patients strictly refuse allogeneic blood transfusion for religious reasons. Nevertheless, JW also wish to benefit from modern therapeutic concepts including major surgical procedures without facing an excessive risk of death. The Northwest Hospital in Frankfurt am Main Germany is a confidential clinic of JW and performs approximately 100 surgical interventions per year on this patient group., Material and Methods: A retrospective analysis of closed medical cases performed in the years 2008-2018 at the Northwest Hospital aimed to clarify (1) the frequency of surgical procedures in JW patients associated with a statistical allogeneic transfusion risk (presence of preoperative anemia and/or in-house transfusion probability >10%) during this time period, (2) the degree of acceptance of strategies avoiding blood transfusion by JW and (3) the anemia-related postoperative mortality rate in JW patients., Results: In the 11- year observation period 123 surgical procedures with a relevant allogeneic transfusion risk were performed in 105 JW patients. Anemia according to World Health Organization (WHO) criteria was present in 44% of cases on the day of surgery. Synthetic and recombinant drugs (tranexamic acid, desmopressin, erythropoetin, rFVIIa) were generally accepted, acute normovolemic hemodilution (ANH) in 92% and cell salvage in 96%. Coagulation factor concentrates extracted from human plasma and therefore generally refused by JW so far, were accepted by 83% of patients following detailed elucidation. Out of 105 JW patients 7 (6.6%) died during the postoperative hospital stay. In 4 of the 7 fatal cases the cause of death could be traced back to severe postoperative anemia., Conclusion: Given optimal management JW patients can undergo major surgery without an excessive risk of death. The 6.6% in-hospital mortality observed in this institution was in the range of the 4% generally observed after surgery in Europe. The majority of JW patients accepted a variety of blood conservation strategies following appropriate elucidation. This also included coagulation factor concentrates extracted from human plasma enabling an effective treatment of even severe bleeding complications. In this analysis postoperative hemoglobin concentrations below 6 g/dl in older JW patients were associated with a high mortality risk due to anemia.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources., (© 2016 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists of Great Britain and Ireland.)

Background: The initial treatment of an acute blood loss with acellular fluids leads to the dilution of the red cell mass remaining in the vasculature, that is, to acute normovolemic anemia. Whether the compensation and, thus, the tolerance of acute anemia, are affected by sympathetic block induced by thoracic epidural anesthesia has not yet been investigated., Methods: Eighteen anesthetized and mechanically ventilated pigs were instrumented with thoracic epidural catheters and randomly assigned to receive an epidural injection of either 5-ml ropivacaine 0.2% (n = 9) aiming for a Th5-Th10 block or saline (n = 9) followed by continuous epidural infusion of 5 ml/h of either fluid. Subsequently, acute normovolemic anemia was induced by replacement of whole blood with 6% hydroxyethyl starch solution until a "critical" limitation of oxygen transport capacity was reached as indicated by a sudden decrease in oxygen consumption. The critical hemoglobin concentration quantified at this time point was the primary endpoint; secondary endpoints were hemodynamic and oxygen transport parameters., Results: Thoracic epidural anesthesia elicited only a moderate decrease in mean arterial pressure and cardiac index and a transient decrease in oxygen extraction ratio. During progressive anemia, the compensatory increases in cardiac index and oxygen extraction ratio were not compromised by thoracic epidural anesthesia. Critical hemoglobin concentration was reached at identical levels in both groups (ropivacaine group: 2.5 ± 0.6 g/dl, saline group: 2.5 ± 0.6 g/dl)., Conclusion: Thoracic epidural anesthesia with ropivacaine 0.2% does not decrease the tolerance to acute normovolemic anemia in healthy pigs. The hemodynamic compensation of acute anemia is fully preserved despite sympathetic block, and the critical hemoglobin concentration remains unaffected.

Introduction: The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O₂) supply during acute normovolemic anemia has not been investigated so far., Methods: Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit). Hbcrit was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O₂-consumption (VO₂). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hbcrit, secondary endpoints were parameters of central hemodynamics, O₂ transport and tissue oxygenation., Results: In each animal, normovolemia was maintained throughout the protocol. Hbcrit was met at 3.7 ± 0.6 g/dl (RS), 3.0 ± 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 ± 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 ± 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO₂), and O₂ extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hbcrit., Conclusions: The choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e.g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function.

Background: Changes in heart rate variability (HRV) during anaesthesia depend on multiple influences such as hypnosis, analgesia, surgical stress, and interacting drugs. Several recent studies have aimed to establish HRV-based monitoring tools to measure perioperative stress or anaesthetic depth. Although hyperoxic ventilation (HV) is known to alter autonomic cardiovascular regulation, there have been no studies investigating its influence on time- and frequency-domain analysis during general anaesthesia. Therefore, we have examined the effects of HV on cardiovascular neuroregulation of anaesthetized patients and conscious volunteers by analysis of relevant HRV parameters., Methods: Fourteen healthy volunteers and 14 anaesthetized, ventilated ASA I patients sequentially breathed room air ( 0.21), pure oxygen ( 1.0), and then room air. During each episode, standardized HRV parameters were calculated from 5 min ECG recordings., Results: HV significantly reduced HR and increased the standard deviation of RR interval values, the root mean square of successive RR interval differences, and the high-frequency (HF) power of the spectral components, whereas the low-frequency (LF) power and the LF/HF ratio of HRV were reduced in both groups. All changes were reversible after was reduced to normoxia., Conclusions: In both healthy volunteers and anaesthetized patients, HV resulted in comparable and reversible changes of established HRV parameters. These changes might be relevant enough to bias HRV-based analgesia and anaesthesia monitoring and could result in a clinically relevant misinterpretation of HRV parameters as indicators of anaesthetic depth during HV.

Aim: Ventilation with pure oxygen (hyperoxic ventilation: HV) is thought to decrease whole body oxygen consumption (VO(2)). However, the validity and impact of this phenomenon remain ambiguous; until now, under hyperoxic conditions, VO(2) has only been determined by the reverse Fick principle, a method with inherent methodological problems. The goal of this study was to determine changes of VO(2), carbon dioxide production (VCO(2)), and the respiratory quotient (RQ) during normoxic and hyperoxic ventilation, using a metabolic monitor., Methods: After providing signed informed consent and institutional acceptance, 14 healthy volunteers were asked to sequentially breathe room air, pure oxygen, and room air again. VO(2), VCO(2), RQ, and energy expenditure (EE) were determined by indirect calorimetry using a modified metabolic monitor during HV., Results: HV reduced VO(2) from 3.4 (3.0/4.0) mL/kg/min to 2.8 (2.5/3.6) mL/kg/min (P < 0.05), whereas VCO(2) remained constant (3.0 [2.6/3.6] mL/kg/min versus 3.0 [2.6/3.5] mL/kg/min, n.s.). After onset of HV, RQ increased from 0.9 (0.8/0.9) to 1.1 (1.0/1.1). Most changes during HV were immediately reversed during subsequent normoxic ventilation., Conclusion: HV not only reduces VO(2), but also increases the respiratory quotient. This might be interpreted as an indicator of the substantial metabolic changes induced by HV. However, the impact of this phenomenon requires further study.

Background: We investigated changes in heart rate variability (HRV) across different degrees of acute dilutional anemia (hemoglobin [Hb]=9, 7, 5, 4, and 3 g/dL) in a pig model., Methods: Twelve anesthetized mechanically ventilated pigs of either gender (mean body weight 27.5±5.5 kg) were hemodiluted by exchange of blood for hydroxyethyl starch (6%; 200000/0.5) from baseline values to each animal's individual critical hemoglobin concentration (Hbcrit 3.3 [2.3/3.6] g/dL). Differences in time- and frequency-domain calculations of HRV were analyzed throughout the hemodilution procedure by using short-term electrocardiogram recordings (analysis of variance+Dunn's post-hoc test)., Results: During the hemodilution procedure, the standard deviation of normal R-R intervals and the coefficient of variation changed at Hb 5.3 (4.2/5.7) g/dL. Thereafter, the high-frequency power (HF), total power of the variance, and root mean square of successive N-N interval differences changed at Hb 3.9 (3.1/4.3) g/dL. The low-frequency power (LF) and the LF/HF ratio remained unaffected by hemodilution to Hbcrit., Conclusion: Acute dilutional anemia resulted in significant changes in different time- and frequency-domain variables in HRV analysis. These changes occurred considerably earlier than did commonly recognized transfusion triggers or signs of general tissue hypoxia. Further investigation is warranted to elucidate whether these changes can be considered as indicators of imminent tissue hypoxia.

Aim of the Study: Recently it has been demonstrated that short term hyperoxic ventilation (HV) can improve glucose metabolism, reduce pulmonary and hepatic apoptosis, and improve gastrointestinal perfusion during acute sepsis. However, it is unknown whether additional O(2) improves survival. Therefore we investigated the effects of increased plasma O(2) on survival during extreme anaemia and concomitant endotoxaemia in order to quantify the efficacy of HV., Methods: Endotoxaemia (Salmonella abortus equi-LPS) was induced in 14 anesthetized pigs ventilated with room air (FiO(2)=0.21). Simultaneously, animals were haemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin concentration (Hb(crit)) was achieved (outermost limit of tissue oxygenation). Subsequently, animals were either ventilated with an FiO(2) of 0.21 (NOX, n=7) or an FiO(2) of 1.0 (HOX, n=7), and observed thereafter for 6 h without further intervention., Results: HV significantly prolonged survival time at Hb(crit) (NOX, 30 [27/35] min; HOX, 172 [111/235] min, p<0.05). In contrast to the NOX group, HV maintained MAP, and improved DO(2) and tissue oxygenation in the HOX group., Conclusion: The improvement of survival, oxygen transport and tissue oxygenation seems to underline the efficacy of HV during endotoxaemia and concomitant acute anaemia. Further studies are needed to transfer these results into daily clinical practice., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

We studied whether low hemoglobin concentrations during normovolemia change the myocardial electrical current (electrocardiogram) in a pig model. Normovolemic anemia was achieved by stepwise replacing blood with colloids (hydroxyethyl starch 6%). We measured the length of the PQ-, QT-, QTc, and the ST interval as well as the amplitude of the Q wave and T wave at hemoglobin concentrations of 9.5, 8.0, 5.5, 3.8, and 3.3 g·dL. Normovolemic anemia is accompanied by a gradual prolongation of the QT and QTc interval and a reduction in the amplitude of the T wave. The QRS complex is partly diminished in amplitude. Results were verified performing a time-frequency analysis on single heartbeats. During severe anemia and normovolemia, electrocardiographic changes can be detected. Further investigations are warranted to elucidate whether these changes indicate myocardial hypoxia.

Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.

Objective: To investigate the efficacy of a polyethylene glycol (PEG) modified formulation of liposome-encapsulated hemoglobin (LEH) as an oxygen-carrying blood substitute in the treatment of critical normovolemic anemia., Design and Setting: Prospective, controlled, randomized experimental study in a university research facility., Subjects: 14 anesthetized and mechanically ventilated beagle dogs., Interventions: Animals were splenectomized and hemodiluted by exchange of whole blood for iso-oncotic hetastarch (HES). Target parameter of the hemodilution protocol was the individual critical hemoglobin concentration (Hb(crit)) corresponding with the onset of O(2) supply dependency of total body O(2) consumption. At Hb(crit) animals were randomized to receive a bolus infusion (20[Symbol: see text]ml/kg) of either LEH (n = 7) or normal saline (NS; n = 7). Subsequently animals were observed without further intervention., Measurements and Results: The primary endpoint was survival time after the completion of treatment; secondary endpoints were parameters of central hemodynamics, O(2) transport and tissue oxygenation. Animals in the LEH group survived significantly longer after completion of treatment (149 +/- 109 vs. 43+/- 56 min). Immediately after treatment LEH-treated animals presented with a more stable cardiovascular condition. After 30 min tissue O(2) tension on the surface of a skeletal muscle was significantly higher in the LEH group (23+/-8 vs. 9 +/- 2 mmHg). Nevertheless, treatment with LEH did not decrease mortality within the observation period., Conclusions: In this present experimental study the infusion of a PEG-modified LEH provided adequate tissue oxygenation, hemodynamic stability, and a prolongation of survival time after critical anemia. However, these effects were sustained for only a short period of time.

Patients admitted to an intensive care unit with the diagnosis "polytrauma" differ from other patients by their typical trauma-associated morbidity (diffusive bleeding, traumatic brain injury, lung contusion), and by the staged surgical treatment of multiple injuries. The complexity of the clinical picture, and the complexity of the chronological order of the operative phases require a close cooperation of the medical specialist disciplines involved. The perioperative morbidity and mortality of polytrauma victims has been reduced significantly within the last 30 years due to an adapted transfusion- and substitution regime (rational utilization of anemia tolerance, calculated substitution of coagulation factors), due to modern therapeutic regimes for the patient with traumatic brain injury (stabilization of cerebral perfusion pressure, stabilization of adequate cerebral oxygenation), and due to the modern therapeutic strategies of mechanical ventilation (lung-protective ventilation, kinetic therapy, non-invasive ventilation). The aim of this review is to describe these modern therapeutic principles of the intensive care unit treatment of the polytrauma patient.

The expected cost explosion in transfusion medicine increases the socio-economic significance of specific institutional transfusion programs. In this context the estimated use of the patient's physiologic tolerance represents an integral part of any blood conservation concept. The present article summarizes the mechanisms, influencing factors and limits of this natural tolerance to anemia and deduces the indication for perioperative red blood cell transfusion. The current recommendations coincide to the effect that perioperative transfusion is unnecessary up to a Hb concentration of 10 g/dl (6.21 mmol/l) even in older patients with cardiopulmonary comorbidity and is only recommended in cases of Hb <6 g/dl (<3.72 mmol/l) in otherwise healthy subjects including pregnant women and children. Critically ill patients with multiple trauma and sepsis do not seem to benefit from transfusions up to Hb concentrations >9 g/dl (>5.59 mmol/l). In cases of massive hemorrhaging and diffuse bleeding disorders the maintenance of a Hb concentration of 10 g/dl (6.21 mmol/l) seems to contribute to stabilization of coagulation.

Inherent risks and increasing costs of allogeneic transfusions underline the socioeconomic relevance of safe and effective alternatives to banked blood. The safety limits of a restrictive transfusion policy are given by a patient's individual tolerance of acute normovolaemic anaemia. latrogenic attempts to increase tolerance of anaemia are helpful in avoiding premature blood transfusions while at the same time maintaining adequate tissue oxygenation. Autologous transfusion techniques include preoperative autologous blood donation (PAD), acute normovolaemic haemodilution (ANH), and intraoperative cell salvage (ICS). The efficacy of PAD and ANH can be augmented by supplemental iron and/or erythropoietin. PAD is only cost-effective when based on a meticulous donation/transfusion plan calculated for the individual patient, and still carries the risk of mistransfusion (clerical error). In contrast, ANH has almost no risks and is more cost-effective. A significant reduction in allogeneic blood transfusions can also be achieved by ICS. Currently, some controversy regarding contraindications of ICS needs to be resolved. Artificial oxygen carriers based on perfluorocarbon (PFC) or haemoglobin (haemoglobin-based oxygen carriers, HBOCs) are attractive alternatives to allogeneic red blood cells. Nevertheless, to date no artificial oxygen carrier is available for routine clinical use, and further studies are needed to show the safety and efficacy of these substances.

Patients with coronary artery disease (CAD) undergoing noncardiac surgery (NCS) pose a special challenge for the anaesthesiologist, as the risk of serious perioperative cardiac complications, which represent a significant cause of morbidity and mortality, is increased in this population. Here we report about a patient with a solitary liver metastasis, who was admitted for hemihepatectomy. The patient with a known single vessel CAD, reporting no current cardiac problems, was cleared for the surgical procedure which carries a high risk of cardiac complications. Cardiology reports were present for evaluation. After an unremarkable placement of the peridural catheter and endotracheal intubation the patient presented with bradycardia and hypotension. Pharmacological resuscitation was initiated. After the patient was stabilized and the differential diagnosis suggested a cardiac problem, surgery was postponed. Following the end of anaesthesia, the patient remained in stable condition without catecholamine support. Coronary angiography on the next day revealed a progression of the CAD. The peridural catheter was removed before the intervention, Aspirin and clopidogrel were given on the same day. The patient was operated successfully without complications six weeks after the coronary intervention.

Background: When initiated in anemic hypoxia, hyperoxic ventilation (ventilation with pure O2, FiO2 1.0, HV) reverses hypoxia-induced ECG-changes and enables survival for several hours. The quantification of the HV-induced gain in anemia tolerance and particularly the Hb-equivalent of HV in this situation are unknown., Methods: Nine anaesthetized pigs were hemodiluted under normoxia (FiO2 0.21) by exchange of whole blood for hydroxyethyl starch (HES) until predefined, ischemia associated ECG-changes occurred (timepoint Hb(crit)). From that time on all animals were ventilated with 100% O2 (FiO2 1.0). In the case of disappearance of the ECG changes with onset of HV, the animals were further hemodiluted until ECG changes reoccurred., Results: HV initiated in anemic hypoxia (Hb 2.3 +/- 0.2 g/dl) improved ECG-readings of all animals, and allowed for a further exchange of 14 +/- 11 ml/kg blood until ECG-changes reoccurred at Hb 1.2 +/- 0.4 g/dl., Conclusion: HV initiated in anemic hypoxia creates a margin of safety for myocardial tissue oxygenation and thus further increases anemia tolerance. The Hb equivalent of HV in this situation amounts to approximately 1g/dl.

Background: Treatment of severe methemoglobinemia includes the avoidance of methemoglobin-inducing drugs, the application of methylene blue, and the administration of supplementary oxygen. However, the efficacy of the latter on oxygen transport, tissue oxygenation, and survival in the treatment of extreme methemoglobinemia is ambiguous. The objective was to assess whether using hyperoxic ventilation as the sole therapeutic intervention (i.e., ventilation with pure oxygen, Fio2 1.0) improves the short-term (6-hr) survival rate during otherwise lethal methemoglobinemia., Design: Prospective, randomized, controlled study., Setting: Experimental animal laboratory of a university hospital., Subjects: Fourteen anesthetized, mechanically ventilated pigs., Interventions: After induction of profound methemoglobinemia (60 +/- 2%) by the injection of 15 mg/kg 4-dimethylaminophenol, artificial ventilation either was continued with room air (G 0.21, n = 7) or was changed over to hyperoxic ventilation (G 1.0, n = 7). A constant level of methemoglobinemia was maintained by continuous infusion of 4-dimethylaminophenol throughout a 6-hr follow-up period., Measurements and Main Results: All animals died within the 6-hr follow-up period, but survival time was prolonged in animals ventilated with pure oxygen (G 0.21, 105 +/- 30 mins; G 1.0, 210 +/- 64 mins, p < .05). No differences were encountered between G 0.21 and G 1.0 with respect to the investigated variables of macrohemodynamics, oxygen transport, and tissue oxygenation., Conclusions: Hyperoxic ventilation has negligible effects on oxygen transport and tissue oxygenation during lethal methemoglobinemia; nevertheless, survival was increased without severe adverse reactions provoked by hyperoxic ventilation.

Background: Ventilation with pure oxygen (hyperoxic ventilation, HV) increases arterial oxygen content (CaO(2)). However HV induces arteriolar constriction and thus potentially affects O(2) supply. We therefore investigated the effects of HV on regional blood flow (RBF) and O(2) supply of different vital organs during moderate normovolaemic anaemia., Methods: Twenty-two anaesthetized dogs were haemodiluted under normoxia (i.e. FiO(2) = 0.21) to a target haemoglobin concentration (Hb) of 7 g dl(-1) and were subsequently ventilated with pure O(2). RBF was determined by use of the radioactive microspheres method in the myocardium, kidney, skeletal muscle, liver, intestine, stomach, and pancreas at Hb = 7 g dl(-1) and after subsequent initiation of HV. RBF in proportion to cardiac output (RBF(relative)), the variation coefficient of RBF (VC) and regional O(2) supply (rDO(2)) were calculated., Results: Initiation of HV at Hb = 7.0 +/- 0.3 g dl(-1) reduced cardiac index (-17%) as well as RBF within the myocardium (-21%), pancreas (-25%), and skeletal muscle (-25%), whereas renal, hepatic, and intestinal RBF remained unchanged. Consequently RBF(relative) of the latter organs increased. Heterogeneity of RBF was marginally affected by HV., Conclusion: The initiation of HV during moderate normovolaemic anaemia (Hb =7 g dl(-1)) was accompanied by RBF redistribution with preference for renal, hepatic and intestinal O(2) supply. Cardiac, pancreatic and muscular O(2) supply decreased, however without any critical restriction of organ function.

Under resting conditions oxygen consumption (VO2) of the tissues equals their O2 demand. However, when oxygen delivery (DO2) decreases below "a critical" value, the consecutive decline of VO2 reflects a critical restriction of DO2 resulting in the onset of tissue hypoxia. Reliable bedside detection of a significant VO2 decline requires continuous measurement of in- and exspiratory O2 concentrations with a metabolic monitor as well as a standardized online analysis of the data obtained. However, for this purpose no standardized procedure was available yet. Therefore, the DeltaCrit-System (DCS) has been developed enabling online detection of a significant VO2 decline indicating critical restriction of DO2. After a reference period with stable VO2 values the DCS tests whether a subsequently measured VO2 value is significantly lower than the mean baseline VO2. A significant VO2 decrease should indicate the onset of O2 supply dependency of VO2 due to a critical restriction of DO2. The DCS has been validated with nine different, artificially generated data sets and has been tested in one animal experiment. DCS has proven consistency and may therefore be considered a new tool allowing clinicians to recognize restrictions in DO2 at an early time, and to start early therapeutic interventions.

Objective: During normovolaemic haemodilution arterial O(2)-content decreases exponentially. Nevertheless, tissue oxygenation is first maintained initially by increased organ perfusion and O(2)-extraction. As soon as these compensatory mechanisms are exhausted, myocardial ischaemia and tissue hypoxia occur at an individual 'critical' haematocrit (Hct) value. This study was conducted in order to assess whether tissue hypoxia at the critical Hct is reversed by hyperoxic ventilation with 100% O(2)., Method: Eighteen anaesthetized pigs were ventilated with room air and were hemodiluted by 1:1 exchange of blood with 6% pentastarch to their individual critical Hct (onset of myocardial ischaemia; significant ECG changes). At the critical Hct, hyperoxic ventilation was initiated. In nine complete datasets, global O(2) delivery and consumption, local tissue O(2) partial pressure (tpO(2)) (MDO-Electrode, Eschweiler, Kiel, Germany) and organ blood flow (microsphere method) in skeletal muscle were analyzed at baseline, after haemodilution to the critical Hct and after 15 min of hyperoxic ventilation., Results: At the critical Hct (7.2+/-1.2%), tpO(2) was reduced from 23+/-3 to 10+/-2 Torr with 50% of all values in the hypoxic range (<10 Torr, all P<0.05). During hyperoxic ventilation, contribution of physically dissolved O(2) to the O(2) delivery and O(2) consumption increased by 400 and 563% (P<0.05) and instantly restored tpO(2) to 18+/-2 Torr, (hypoxic values 25%, P<0.05)., Conclusion: Hyperoxic ventilation reversed tissue hypoxia at the critical Hct due to preferential utilization of plasma O(2) and allowed temporary preservation of tissue oxygenation. During haemodilution, hyperoxic ventilation might offer an effective bridge until red cells are ready for transfusion.

Background: When O2-delivery to tissues is critically reduced, O2-consumption becomes dependent on O2-delivery and starts to decline, which reflects tissue hypoxia. In order to timely detect tissue hypoxia prior to organ damage, O2-consumption may be calculated or measured from respiratory gases. We have assessed reproducibility of calculated and measured O2-consumption-data and their agreement during O2-supply-dependency., Method: Data of 31 anesthetized, ventilated pigs were analysed retrospectively. Animals had undergone either controlled hemorrhage ("shock") or isovolemic exchange of blood with colloids (extreme hemodilution, "HD") until O2-consumption had become dependent on O2-delivery. O2-consumption was calculated from the Fick equation and measured simultaneously with a DELTATRAC II metabolic monitor. Repeatability was determined for (1) calculated and (2) for measured.VO2 -values and (3) for input variables of the Fick equation (i.e. cardiac index (CI) and arteriovenous O2-content difference (CaO2-CvO2)). Bias between calculated and measured data and precision of calculation were assessed from paired O2-consumption-values obtained before and after induction of O2-supply-dependency via hemorrhage or extreme hemodilution., Results: Repeatability of the reversed Fick method was inferior to repeatability of measurement (27 vs 15%) due to error propagation from CI and (CaO2-CvO2). Between-method-bias at baseline ("BL") was 3%, and changed in case of O2-supply-dependency (shock -15%; HD -31%, both p<0.05 vs BL), precision of the reversed Fick method deteriorated (BL 32%; shock 60%; HD 60%) due to variability of CI (CV: 16%; shock 27%; HD 41%)., Conclusion: In anesthetized pigs calculated and measured O2-consumption values are in agreement, while in presence of O2-supply-dependency the reversed Fick method (1) grossly underestimates true O2-consumption and (2) precision deteriorates not allowing to verify or reject the presence of tissue hypoxia.

Background: Gastric tonometry is intended to reveal alterations in splanchnic perfusion and oxygenation. Based on the tonometric measurement of gastric mucosal partial pressure of carbon dioxide (pCO(2)) and the simultaneous determination of arterial blood gas parameters (bicarbonate concentration [HCO(3-)], pH and pCO(2)), several parameters can be calculated., Aims: To identify the most suitable tonometric parameter [gastric mucosal pH (pH(i)), intramucosal pCO(2) (p(i)CO(2)), the difference between tonometric and arterial pCO(2) concentrations (pCO(2) gap), [H+] gap] that reliably reflects gastric hypoperfusion and hypoxia during severe haemorrhagic shock., Design: Randomised, controlled experimental study., Methods: An artificial stenosis of the left anterior descending coronary artery (LAD) was induced. Subsequently, the animals were haemorrhaged to a mean arterial pressure of 45 mmHg, which was maintained for 60 min., Measurements and Main Results: Tonometric measurements were performed in 17 land-race pigs before and after induction of LAD stenosis and after haemorrhagic shock. P values obtained using the Wilcoxon signed-rank testing were used to compare the level of significance for the tonometric parameters and the corresponding arterial blood gas values [arterial pCO2 (p(a)CO(2)), [HCO(3-)], arterial pH (pH(a))]. While induction of critical coronary stenosis did not provoke any changes, all parameters changed significantly during haemorrhagic shock. The lowest P value was found for pH(i) (P=0.00013) followed by [H+ gap] (P=0.0005). P values higher by a factor of ten were found for pCO(2) gap (P=0.00119) and were highest for p(i)CO(2) (P=0.00562). P values of the corresponding arterial blood gas parameters were lower by a factor of ten than the P value of p(i)CO(2)., Conclusion: pH(i), pCO(2) gap and [H+] gap are considerably influenced by changes of systemic arterial blood gas values. This is demonstrated by lower P values of the corresponding arterial blood gas values in comparison with p(i)CO(2). Therefore pH(i), pCO(2) gap and [H+] gap seem to indicate more likely systemic changes, whereas p(i)CO(2) appears to reflect disturbances of regional gastric tissue perfusion and oxygenation more reliably than any other derived tonometric parameter.

Background: Normovolemic hemodilution is an effective strategy to limit perioperative homologous blood transfusions. The reduction of hematocrit related to hemodilution results in reduced arterial oxygen content, which initially is compensated for by an increase in cardiac output and oxygen extraction ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and tissue hypoxia., Objective: To assess whether hemodilution can be extended to lower hematocrit values by the use of a hemoglobin-based artificial oxygen carrier solution., Design: Prospective, randomized, controlled., Setting: Animal laboratory of a university hospital., Subjects: Twelve anesthetized, mechanically ventilated pigs., Interventions: Isovolemic hemodilution was performed with either 10% diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, CO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healthcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%., Measurements and Main Results: In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (significant ST-segment depression >0.1 mV and/or arrhythmia). To determine peripheral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue oxygen partial pressure (tPo2, MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventricular (LV) end-diastolic pressure, global and regional myocardial contractility (maximal change in pressure over time, LV segmental shortening, microsonometry method), LV myocardial blood flow (fluorescent microsphere technique), LV oxygen delivery, and the ratio between LV subendocardial and subepicardial myocardial perfusion. In the HSA group, critical hematocrit was found at 6.1 (1.8)% (hemoglobin, 2 g x dL(-1)), whereas all DCLHb-treated animals survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g x dL(-1)) was achieved without signs of hemodynamic instability. Although arterial oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL-1) neither oxygen delivery and oxygen uptake nor median tPo2 and hypoxic tPo2 values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals until 1.2% hematocrit was achieved. This was attributable to a higher coronary perfusion pressure (65 (22) mm Hg vs. 19 (8) mm Hg; p <.05), higher subendocardial perfusion (4.1 (2.6) mL.min-1.g-1 vs. 1.2 (0.4) mL x min(-1) x g(-1)), and subendocardial oxygen delivery (5.7 (2) mL x min(-1) x g(-1), p <.05) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (730); p <.05) and higher regional myocardial contractility (11 (8)% vs. 6 (2)%; p <.05). An increased LV end-diastolic pressure reflected LV myocardial pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted animals. In the DCLHb group, systemic vascular resistance index remained at baseline values throughout the protocol, whereas coronary vascular resistance decreased. In contrast, both variables decreased in HSA-diluted animals., Conclusion: DCLHb as a diluent allowed for hemodilution beyond the hematocrit value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). Even at 1.2% hematocrit (hemoglobin, 4.7 g x dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxygenation. This discrepancy in regional oxygenation might be caused by a redistribution of blood flow favoring the heart, which is related to a disproportionate decrease of coronary vascular resistance index during hemodilution with DCLHb.

As an alternative to transfusion of red blood cells, intravenously (iv) administered artificial oxygen (O(2)) carriers are intended to increase the reduced O(2) carrying capacity of blood in the case of acute severe anemia, i.e. hemorrhagic shock or extreme normovolemic hemodilution (ANH). Actually, two groups of artificial O(2) carriers are investigated: ultrapurified, stroma-free hemoglobin solutions (SFH) of human or bovine origin and synthetically produced perfluorocarbons (PFC). SFH may be administered in large amounts and are suitable for 1:1 replacement of blood losses in case of hemorrhage as well as for isovolemic exchange of blood during ANH. In both situations SFH solutions effectively restore (hemorrhagic shock) and maintain (extreme ANH) tissue oxygenation despite extremely low hematocrit values. The vasopressor property of the isolated Hb molecule leads to a species-dependent (rodent>pig>human) increase in systemic and pulmonary vascular resistance, but leaves overall distribution of cardiac output uninfluenced. Due to the particulate nature of PFC emulsions, iv administration has to be restricted to small doses (3-4.5 ml/kg body weight for the actually investigated 60% w/v perflubron emulsion) in order to avoid overload of the reticuloendothelial system. Thus PFC emulsions are unsuitable for isovolemic blood replacement in hemorrhagic shock or ANH. Low-dose iv PFC administration in already hemodiluted subjects, however, creates an additional margin of safety to guarantee adequate tissue oxygenation which allows for further, extreme ANH, without risking tissue hypoxia.

Hemorrhagic shock alters heterogeneity of regional myocardial perfusion (RMP) in the presence of critical coronary stenosis in pigs. Conventional resuscitation has failed to reverse these effects. We hypothesized that improvement of the resuscitation regime would lead to restoration of RMP heterogeneity. Diaspirin-cross-linked hemoglobin (10 g/dl; DCLHb) and human serum albumin (8.0 g/dl; HSA) were used. After baseline, a branch of the left coronary artery was stenosed; thereafter, hemorrhagic shock was induced. Resuscitation was performed with either DCLHb or HSA. At baseline, the fractcal dimension (D) of subendocardial myocardium was 1.31 +/- 0.083 (HSA) and 1.35 +/- 0.106 (DCLHb) (mean +/- SD). Coronary stenosis increased subendocardial D slightly but consistently only in the DCLHb group (1.39 +/- 0.104; P < 0.05). Shock reduced subendocardial D: 1.21 +/- 0.093 (HSA; P = 0.10), 1.25 +/- 0.092 (DCLHb; P < 0.05). Administration of DCLHb increased subendocardial D in 7 of 10 animals (1.31 +/- 0.097; P = 0.066). HSA was ineffective in this respect. DCLHb infusion restored arterial pressure and increased cardiac index (CI) to 80% of baseline values. Administration of HSA left animals hypotensive (69 mmHg) and increased CI to 122% of the average baseline value. Shock-induced disturbances of the distribution of RMP were improved by administration of DCLHb but not by HSA.

Background: A clinically relevant increase of PaO subset2 or decrease of pulmonary vascular resistance (PVR) upon inhalation of NO (iNO) does occur in only 60 to 80% of patients with acute lung injury. The mechanisms for divergent responses of different patients have not yet been fully elucidated. Since NO mediates its pulmonary effects by stimulating soluble guanylate cyclase, thereby increasing levels of cyclic guanosinemonophosphate (cGMP), we hypothesized that pulmonary cGMP production upon iNO might be suppressed in patients not responding to iNO treatment., Methods: After approval by the local ethical committee and after informed consent had been obtained, both arterial and mixed-venous cGMP levels were analyzed in 13 patients in whom iNO was administered to treat pulmonary hypertension and/or hypoxemia due to acute respiratory distress syndrome (n = 11) or reperfusion injury following lung transplantation (n = 2). Both cardiorespiratory variables and cGMP concentrations were documented simultaneously at baseline, 15 min after inhalation of 8 ppm of NO, and 15 min after withdrawal of NO, respectively., Results: Inhaled NO resulted in a significant increase in PaO(2)/FiO(2) and a decrease in PVR. Arterial and mixed venous concentration of cGMP (median) also increased significantly upon iNO from 2.5 to 6.5 nM (p <0.05) and from 3.0 to 5.7 nM (p <0.05), respectively. Theses effects were fully reversible after withdrawal of iNO. No gradients between arterial and mixed venous cGMP concentrations were detected (p = 0.12). Regression analysis showed no relationship between baseline arterial cGMP concentrations and changes of either PaO(2)/FiO(2) (p = 0. 62) or PVR (p = 0.91). Similarly, no relationship was found between the rise of arterial cGMP concentration subsequent to iNO and corresponding changes of PaO(2) (p = 0.40) or PVR (p = 0.74), respectively., Conclusion: Inhalation of NO significantly stimulates soluble guanylate cyclase within the lungs in patients with acute lung injury. However, neither baseline cGMP nor its rise during treatment with inhaled NO can predict the clinical efficacy of iNO in humans. Furthermore, the fact that increased cGMP concentrations were detected during administration of iNO in mixed venous blood (i.e. pulmonary inflow) strongly suggest that the pharmacological effects of iNO are not fully selective for the lungs, but may also affect extrapulmonary organs.

Acute normovolemic hemodilution (ANH) is efficient in reducing allogenic blood transfusion needs during elective surgery. Tissue oxygenation is maintained by increased cardiac output and oxygen extraction and, presumably, a more homogeneous tissue perfusion. The aim of this study was to investigate blood flow distribution and oxygenation of skeletal muscle. ANH from hematocrit of 36 +/- 3 to 20 +/- 1% was performed in 22 splenectomized, anesthetized beagles (17 analyzed) ventilated with room air. Normovolemia was confirmed by measurement of blood volume. Distribution of perfusion within skeletal muscle was determined by using radioactive microspheres. Tissue oxygen partial pressure was assessed with a polarographic platinum surface electrode. Cardiac index (3.69 +/- 0.79 vs. 4.79 +/- 0.73 l. min-1. m-2) and muscle perfusion (4.07 +/- 0.44 vs. 5.18 +/- 0.36 ml. 100 g-1. min-1) were increased at hematocrit of 20%. Oxygen delivery to skeletal muscle was reduced to 74% of baseline values (0.64 +/- 0.06 vs. 0.48 +/- 0.03 ml O2. 100 g-1. min-1). Nevertheless, tissue PO2 was preserved (27.4 +/- 1.3 vs. 29.9 +/- 1. 4 Torr). Heterogeneity of muscle perfusion (relative dispersion) was reduced after ANH (20.0 +/- 2.2 vs. 13.9 +/- 1.5%). We conclude that a more homogeneous distribution of perfusion is one mechanism for the preservation of tissue oxygenation after moderate ANH, despite reduced oxygen delivery.

The expected explosion of costs in transfusion medicine due to the shortfall of healthy donors and the more frequent treatment of transfusion-associated complications (chronic hepatitis, cirrhosis, wound infection, tumor recurrence) increases the socio-economic importance of the development of safe and effective synthetic oxygen carriers as an alternative to the transfusion of homologous red blood cells. Currently two types of artificial oxygen carriers are experimentally and clinically investigated for their capacity to ensure adequate tissue oxygenation in the case of severe anemia. In addition to their oxygen transport capacity solutions based on free human or bovine hemoglobin provide vasoconstrictor properties. Their hyperoncotic properties make them particularly attractive for the treatment of severe hemorrhagic shock. Perfluorocarbon (PFC) emulsions allow an increase of the physically dissolved portion of arterial oxygen content. Due to their particulate nature (emulsion droplets) PFC may only be infused in low doses. Otherwise there is risk of overload and malfunction of phagocytic cells of the reticulo-endothelial system. In the case of an intraoperative blood-loss in preoperatively hemodiluted patients, bolus infusion of PFC represents an effective means to avoid immediate retransfusion of autologous blood and allows for further, extreme hemodilution without risking tissue hypoxia.

Background: Human recombinant interleukin-10 (rhIL-10) has been found to inhibit endotoxin-induced production of several proinflammatory cytokines including tumor necrosis factor alpha (TNFalpha) from human monocytes. The exogenous therapeutic administration of rhIL-10 in acute and chronic hyperinflammatory conditions has been discussed. For none of the large animal species that have been used to study the role and effects of various mediators during septicemia, crossreactivity of rhIL-10 has been shown so far. Therefore, the aim of the present investigation was to evaluate the crossreactivity of rhIL-10 in a porcine model., Methods: To determine the effects of rhIL-10 on endotoxin-challenged porcine monocytes, we incubated porcine peripheral blood monocytes from five donors with three different concentrations of rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml, respectively) either simultaneously with, or two hours prior to lipopolysaccharide (LPS) administration., Results: As compared to incubation with LPS (1 microg/ml) alone, coincubation with LPS and rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml) (n = 5) for four hours resulted in a marked and uniform reduction of immunoreactive TNFalpha. For preincubation (n = 5), only the addition of 500 ng/ml rhIL-10 led to a homogeneous decrease of TNFalpha levels in each sample. There was no consistent reduction in TNFalpha after preincubation with 1000 and 2000 ng/ml rhIL-10. Our results indicate crossreactivity of recombinant human interleukin-10 in porcine peripheral blood monocytes. Further investigations on the potential therapeutical role of exogenously administered rhIL-10 are thus possible in porcine models.

Objectives: To evaluate the effects of inhaled prostacyclin (PGI2) and inhaled as well as intravenous prostaglandin E1 (PGE1) on thromboxane A2 mimetic-induced pulmonary vasoconstriction. Active pulmonary vasoconstriction was to be distinguished from passive resistance to blood flow., Design: Prospective, randomized, crossover study., Setting: Experimental animal laboratory., Subjects: Eight anesthetized and paralyzed sheep., Interventions: The stable thromboxane A2 mimetic, U46619, was infused in increasing dosage to obtain a stable pulmonary hypertension of approximately 30 mm Hg. Subsequently, PGE1 aerosol (0.6, 6, 58, 259 ng/kg/min), intravenous PGE, (0.5 microg/kg/min), or PGI2 aerosol (27 ng/kg/min) were administered in randomized order., Measurements and Main Results: Active pulmonary vasoconstriction was assessed by determining the pulmonary pressure-flow relationship (PPFR). For measurement of pulmonary artery flow, an ultrasound flow probe was placed around the pulmonary artery after a sternotomy. Pulmonary arterial pressure was measured with a pulmonary artery flotation catheter. Flow was varied by partial occlusion of the inferior vena cava or incremental opening of an arterio-venous fistula between the large neck vessels. The primary end points were the slope of the resulting linear pressure-flow relationship, and pulmonary vascular resistance (PVR). Infusion of U46619 increased the slope of the PPFR (2.9+/-0.7 vs. 4.2+/-1.2 mm Hg/L/min [median+/-semi-interquartile range]; p < or = .05), and PVR (221+/-20 vs. 424+/-57 dyne x sec/cm5) (p < .05). Neither dose of PGE1 aerosol induced changes of the slope of PPFR or PVR. In contrast, intravenous administration of the same drug reduced the slope of the PPFR (4.0+/-1.0 vs. 3.1+/-0.4) (p < .05) but left PVR unchanged. Inhalation of PGI2 reduced both the slope of the PPFR, slightly but significantly, and PVR (424+/-98 vs. 323+/-26 dyne x sec/cm5) (p < .05)., Conclusions: This study is the first to show reduction of active pulmonary vasoconstriction by PGI2 aerosol. Neither inhalation nor intravenous administration of PGE1 reduced PVR but the latter reduced the slope of PPFR. We conclude that PGE1 has potential for pulmonary vasodilation, but that it is ineffective as an aerosol, even in high doses, in sheep. PVR may fail to reflect drug-induced pulmonary vasodilation.

Clinicians lack a practical method for measuring CBF rapidly, repeatedly, and noninvasively at the bedside. A new noninvasive technique for estimation of cerebral hemodynamics by use of near-infrared spectroscopy (NIRS) and an intravenously infused tracer dye is proposed. Kinetics of the infrared tracer indocyanine green were monitored on the intact skull in pigs. According to an algorithm derived from fluorescein flowmetry, a relative blood flow index (BFI) was calculated. Data obtained were compared with cerebral and galeal blood flow values assessed by radioactive microspheres under baseline conditions and during hemorrhagic shock and resuscitation. Blood flow index correlated significantly (rs = 0.814, P < 0.001) with cortical blood flow but not with galeal blood flow (rs = 0.258). However, limits of agreement between BFI and CBF are rather wide (+/- 38.2 +/- 6.4 mL 100 g-1 min-1) and require further studies. Data presented demonstrate that detection of tracer kinetics in the cerebrovasculature by NIRS may serve as valuable tool for the noninvasive estimation of regional CBF. Indocyanine green dilution curves monitored noninvasively on the intact skull by NIRS reflect dye passage through the cerebral, not extracerebral, circulation.

Intact cardiac compensatory mechanisms are necessary to maintain adequate tissue oxygenation during acute normovolemic hemodilution (ANH). Left ventricular (LV) perfusion, oxygenation and function were analyzed in an experimental whole-body model of profound ANH (Hct 9%) and effectiveness of a perfluorocarbon-based oxygen carrier in maintaining myocardial oxygenation and function was evaluated. A total of 22 anesthetized dogs were hemodiluted to Hct 20% followed by a simulated, controlled blood-loss phase in which dogs were randomized to either: (1) 1:1 exchange of lost blood with autologous red blood cells (RBC-group), (2) 1:1 exchange with a colloid (control-group) and (3) 1:1 exchange with a colloid after a single dose of 1.8 g/kg BW perflubron i.v. (PFC-group). Myocardial oxygen delivery and consumption as well as endocardial perfusion were determined using radioactive microspheres. LV myocardial contractility (LV MC) was assessed from: (1) the relationship between maximum rate of LV pressure increase (LVdp/dtmax) and LV enddiastolic volume (LVEDV) and (2) analysis of the LV endsystolic pressure volume relationship (ESPVR). LV diastolic properties were reflected by (1) minimum rate of LV pressure increase (LVdp/dtmin), (2) slope and intercept of the enddiastolic pressure-volume relationship (EDPVR) and (3) the time-constant of isovolumic LV pressure decline "tau 1/2". Full sets of LV MC data were obtained from 18 dogs (n = 6 per group). LV MC (LVdp/dtmax-LVEDV relation) increased after perflubron administration. At the lowest Hct level, all parameters reflecting LV MC as well as LVdp/dtmin were significantly higher in the PFC-group than in the control-group. After profound normovolemic hemodilution (Hct 9%) superiority of LV MC and LV diastolic properties was found, when myocardial oxygenation was supported by i.v. perflubron emulsion, a temporary O2 carrier.

Background: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system., Study Design and Methods: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an intraoperative volume-compensated blood loss was simulated. The efficacy of three therapeutic regimens in maintaining tissue oxygenation was compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of autologous RBCs; 2) PFC group (n = 7): bolus application of a second-generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and tissue oxygenation were assessed., Results: Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood loss. In the PFC and control groups, heart rate and cardiac index increased significantly in response to further ANH. Tissue oxygenation was not different in the PFC and the RBC groups. Direct comparison of the PFC and control groups revealed better tissue oxygenation in the PFC group, as reflected by significantly higher mixed venous, coronary venous, and local tissue pO2 on liver and skeletal muscle., Conclusion: Bolus intravenous administration of 60-percent (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to one of 3 g per dL were as effective as autologous RBC transfusion in maintaining tissue oxygenation during volume-compensated blood loss designed to mimic surgical bleeding.

In seven anesthetized dogs, the effects of acute normovolemic hemodilution (ANH) to a hematocrit of 20 and 8% and the effects of hyperoxic ventilation (100% oxygen) on distribution of regional pulmonary blood flow (rPBF; radioactive microspheres) were investigated. Normovolemia was monitored with blood volume measurements (indocyanine green dilution kinetics). Before ANH, fractal dimension (D) of rPBF in the whole lung was 1.19 +/- 0.09 (mean +/- SD). Spatial correlation (rho) of rPBF in the whole lung was 0.6 +/- 0.08. D is a resolution-independent measure for global rPBF distribution, and rho is the averaged flow relationship of directly neighboring lung samples. With regard to the entire lung, neither ANH nor hyperoxia changed D or rho. With regard to horizontal, isogravitational planes, ANH induced opposite changes of rPBF heterogeneity depending on the vertical location of the plane and the parameter used. In ventral planes, a change in relative dispersion (SD/mean) indicated decreased homogeneity. However, rho suggested more homogeneous perfusion. Hyperoxia restored baseline rPBF distribution. Our data suggest that ANH causes different alterations of heterogeneity of rPBF depending on location within the lung.

Background: In subjects who have undergone acute preoperative normovolemic hemodilution (ANH), intraoperative hemorrhage is generally treated by immediate return of autologous blood collected during ANH. Simply increasing blood oxygen content by hyperoxic ventilation (HV, inspiratory fraction [FIO2] 1.0) might compensate for the acute anemia, allow further ANH, and delay onset of autologous blood return., Study Design and Methods: This study 1) evaluated the effects of HV (FIO2 1.0) upon ANH to a hemoglobin (Hb) concentration of 7 g per dL in anesthetized dogs ventilated with room air and 2) compared the effects of subsequent profound ANH (Hb, 3 g/dL) with and without an intravenous perfluorocarbon emulsion (perflubron 60% wt/vol) versus those of autologous red cell transfusion. The results of the entire study are presented in two parts. Organ tissue oxygenation was assessed in skeletal muscle and liver, and systemic oxygenation status was evaluated. Myocardial contractility was deduced from left ventricular pressure-volume relationship. Seven of 22 dogs underwent further hemodilution while breathing 100-percent O2, for a determination of the Hb concentration at which HV-induced effects were abolished., Results: HV completely reversed the ANH-induced increase in cardiac index (4.6 +/- 0.7 vs. 3.8 +/- 0.9 L/min/m2 before and during HV; p < 0.05) and partially reversed the decrease in systemic vascular resistance (1784 +/- 329 vs. 2087 +/- 524 dyn x cm-5 x sec x m-2; p < 0.05). Despite unchanged global O2 delivery, organ tissue oxygenation improved during HV (mixed venous partial pressure of O2: 40 +/- 3 vs. 59 +/- 7 torr; coronary venous pressure of O2: 30 +/- 4 vs. 43 +/- 6 torr; p < 0.05; liver surface: 31 +/- 11 vs. 39 +/- 13 torr; skeletal muscle surface: 30 +/- 14 vs. 41 +/- 22 torr; p < 0.05). This improvement was due to an increased contribution of physically dissolved O2 in plasma to O2 delivery (3.2 +/- 0.2% before HV vs. 14.6 +/- 1% during HV; p < 0.05) and O2 consumption (whole body: 6 +/- 1% vs. 47 +/- 8%, p < 0.05; myocardium: 4.3 +/- 0.9% vs. 31 +/- 6%, p < 0.05). The beneficial effects of HV were lost after an additional volume-compensated exchange of 19 percent of blood volume (Hb, 5.6 g/dL)., Conclusion: In anesthetized dogs ventilated with room air and hemodiluted to a Hb of 7 g per dL, simple oxygen therapy by HV (FIO2 1.0) rapidly improves tissue oxygenation and permits extended hemodilution to Hb of 5.8 g per dL until the HV-induced effects are lost.