Improve Tissue Oxygenation Research Articles

Traumatic brain injury and severe uncontrolled haemorrhage with short delay pre-hospital resuscitation in a swine model

IntroductionUnavailability of blood (and oxygen delivery) for pre-hospital resuscitation in haemorrhagic shock patients are major problems, supporting the importance for novel resuscitation strategies. In a combined polytrauma model of uncontrolled haemorrhage and traumatic brain injury (TBI) in swine, we investigated if pre-hospital administration of the haemoglobin based oxygen carrier HBOC-201 will improve tissue oxygenation and physiologic parameters compared to Lactated Ringer's (LR) solution. Materials and methodsAnaesthetised Yorkshire swine underwent fluid-percussion TBI and Grade III liver laceration. During a 30-min pre-hospital phase, the animals were resuscitated with a single infusion of HBOC-201, LR solution, or nothing (NON). Upon hospital arrival, the animals were given blood or normal saline as needed. Surviving animals were euthanised 6h post-injury. Cerebral blood flow was measured by microsphere injection, and pathology was assessed by gross observation and immunohistochemical analysis. ResultsMean TBI force (2.4±0.1atm) (means±standard error of the mean) and blood loss (22.5±1.7mL/kg) were similar between groups. Survival at the 6h endpoint was similar in all groups (∼50%). Cerebral perfusion pressure (CPP) and brain tissue oxygen tension were significantly greater in HBOC-201 as compared with LR animals (p<0.005). Mean arterial pressure (MAP) and mean pulmonary artery pressure (MPAP) were not significantly different amongst groups. Blood transfusion requirements were delayed in HBOC-201 animals. Animals treated with HBOC-201 or LR showed no immunohistopathological differences in glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP-2). Severity of subarachnoid and intraparenchymal haemorrhages were similar for HBOC and LR groups. ConclusionIn this polytrauma swine model of uncontrolled haemorrhage and TBI with a 30-min delay to hospital arrival, pre-hospital resuscitation with one bolus of HBOC-201 indicated short term benefits in systemic and cerebrovascular physiological parameters. True clinical benefits of this strategy need to be confirmed on TBI and haemorrhagic shock patients.

Transfusion of Stored Red Blood Cells in Critical Illness: Impact on Tissue Oxygenation

Blood transfusion is a common requirement in the intensive care setting. Improved tissue oxygenation is the therapeutic objective of transfusion for normovolaemic anaemia. However, the efficiency with which red blood cells (RBCs) carry oxygen to the tissues has been questioned, particularly after prolonged storage. We measured the impact on oxygen transport variables (base excess, lactate and ScvO2) of transfusion of a unit of stored RBCs in 45 critically ill adults. There were no significant changes in these variables, except for ScvO2, which increased with older units (≥ 20 days storage), suggesting impaired oxygen uptake by the tissues. The role of the storage lesion (structural and functional changes in the RBC acquired in storage media) is discussed with reference to its impact on oxygen delivery.

Pre‐oxygenation in healthy volunteers: a comparison of the supine and 45° seated positions*

Pre-oxygenation in the seated (sitting) position has been associated with better oxygenation. This randomised, cross over study compared oxygenation in the supine position with that in the 45° seated position in 40 young, healthy volunteers. Oxygen was administered through a circle system and tight fitting facemask. Transcutaneous P(O)₂ levels were recorded at 10-s intervals from two measurement points during 4 min of oxygenation in the two positions. The mean (SD) values of 12 measurements taken between the third and fourth minute were recorded. There was no difference in the increase in tissue oxygenation when comparing the supine and seated positions (32.7 (7.3) vs 32.6 (6.7) kPa, respectively). We conclude that there is no evidence that pre-oxygenation in the 45° seated position improves tissue oxygenation in young healthy volunteers compared with the supine position.

LEVOSIMENDAN INCREASES PORTAL BLOOD FLOW AND ATTENUATES INTESTINAL INTRAMUCOSAL ACIDOSIS IN EXPERIMENTAL SEPTIC SHOCK

It has been proposed that vasodilatory therapy may increase microcirculatory blood flow and improve tissue oxygenation in septic shock. The authors aimed to evaluate the effects of levosimendan in systemic and splanchnic hemodynamics in a porcine model of septic shock in a randomized animal controlled study. This study was performed in an animal research facility in a university hospital. Anesthetized pigs were monitored with a pulmonary artery catheter and an ultrasonic blood flow probe in the portal vein for measurement of systemic and portal blood flows and with a tonometer placed in the small intestine for measurement of the intramucosal-arterial PCO2 gap. Three groups of pigs were studied: nonseptic (n = 7), septic (n = 7), and septic treated with levosimendan (n = 7). Levosimendan was administered i.v. at t = -10 min (200 microg/kg in i.v. bolus followed by 200 microg/kg per h). Sepsis was induced at t = 0 min by the administration of live Escherichia coli. Vascular reactivity was tested by the hemodynamic response to noradrenaline. Levosimendan markedly attenuated the sepsis-induced increase in pulmonary vascular resistance, decrease in portal/systemic blood flow, oliguria, impairment in oxygenation, hyperkalemia, and the widened intramucosal-arterial PCO2 gap. Systemic blood pressure and vascular resistance did not differ as compared with the septic untreated group. Responses to noradrenaline significantly improved in animals treated with levosimendan. Treatment with levosimendan in this animal model of sepsis attenuated pulmonary vasoconstriction and improved portal blood flow, intestinal mucosal oxygenation, pulmonary function, and vascular reactivity.

Neuraxial Anesthesia and Surgical Site Infection

Neuraxial Anesthesia and Surgical Site Infection

Regional High-Flow Cerebral Perfusion Improves Both Cerebral and Somatic Tissue Oxygenation in Aortic Arch Repair

Regional cerebral perfusion provides cerebral circulatory support during aortic arch reconstruction. We report the effectiveness of high-flow regional cerebral perfusion (HFRCP) from the right innominate artery to maintain sufficient cerebral and somatic oxygen delivery through collateral vessels. Frontal cerebral and thoracolumbar probes to measure somatic regional oxygen saturation (rSo(2)) were used to continuously measure oxygenation during cardiopulmonary bypass in 18 patients (weight, 2.1 to 4.3 kg) who underwent arch reconstruction using HFRCP (mean flow, 82; range, 43 to 108 ml/kg/min). Procedures included 9 Norwood procedures, 5 coarctation of aorta/interruption of aorta complex repairs, and 4 aortic arch repairs for a single ventricle. Mean HFRCP duration was 51 + or - 17 minutes under moderate hypothermia. Mean radial arterial pressure was kept at less than 50 mm Hg during HFRCP, and chlorpromazine (mean dose, 2.8 mg/kg) was given to all patients before and during HFRCP to increase regional cerebral perfusion flow. Plasma lactate concentration was measured before and after HFRCP. During HFRCP, mean cerebral rSo(2) was 78.8% + or - 9.5%, somatic rSo(2) was 65.4% + or - 12.1%, and lactate concentration increased from 3.8 + or - 2.2 to 5.5 + or - 2.1 mmol/L. There was significant correlation between regional cerebral perfusion flow and somatic rSo(2). Significant inverse correlations were noted between regional cerebral perfusion flow and the increase of lactate concentration and between somatic rSo(2) and the increase of lactate concentration. High-flow regional cerebral perfusion preserved sufficient cerebral and somatic tissue oxygenation during aortic arch repair. The reduction of vascular resistance of collateral vessels increased both cerebral and somatic blood flow, resulting in improved tissue oxygen delivery.

Serum levels of VEGF and bFGF in hypoxic patients with exacerbated COPD

Hypoxia frequently complicates the course of chronic obstructive pulmonary disease (COPD). Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the two most potent angiogenic factors and may play a role in adaptation to hypoxia. The aims of the study were to assess the serum levels of VEGF and bFGF and to evaluate their mutual relationship in hypoxic patients with exacerbated COPD. The study group consisted of 50 hypoxic (PaO(2) 53 mmHg) patients with exacerbated COPD. Control groups were 30 stable COPD patients with PaO(2) 70 mmHg, and 30 healthy blood donors. The serum concentrations of VEGF and bFGF were measured using commercial enzyme-linked immunoassay kits. Patients with exacerbated COPD had significantly higher serum VEGF levels (1,089.16 +/- 1,128.03 pg/mL) compared to those with stable COPD (197.68 +/- 178.06 pg/mL) (p < 0.0001) and healthy blood donor group (257.69 +/- 170.4 pg/mL) (p < 0.0001). Serum bFGF levels were significantly higher in the exacerbated COPD group (6.15 +/- 2.56 pg/mL) compared to control groups (p = 0.0001). Basic FGF was undetectable in the stable COPD and blood donor groups. Since VEGF and bFGF correlated significantly with the majority of factors investigated in COPD patients, multivariate analysis was performed. According to the step-wise regression analysis, VEGF was best determined by PaO(2), WBC and IL-6. Basic FGF was best determined by PaO(2) and pH. The highly significant, simple correlation between VEGF and bFGF was lost in multivariate analysis. This suggests that their correlation is not independent, but due to factors that remain in the model after step-wise regression. These are essentially linked to the level of hypoxia. Results of our study suggest that VEGF and bFGF production is stimulated in hypoxic patients with exacerbated COPD. Elevated levels of VEGF and bFGF may activate the process of neoangiogenesis, which may lead to increased perfusion and an improvement in tissue oxygenation in this group of patients.

Anemia Management in Chronic Kidney Disease: Bursting the Hemoglobin Bubble

In this issue, Palmer and colleagues' meta-analysis confirms earlier findings of harms associated with ESAs in patients with CKD. Remaining questions include whether there is a lower hemoglobin lim...

Controversies related to red blood cell transfusion in critically ill patients

To review the evolution of and controversies associated with allogenic blood transfusion in critically ill patients. Veterinary and human literature review. RBC transfusion practices for ICU patients have come under scrutiny in the last 2 decades. Human trials have demonstrated relative tolerance to severe, euvolemic anemia and a significant outcome advantage following implementation of more restricted transfusion therapy. Investigators question the ability of RBCs stored longer than 2 weeks to improve tissue oxygenation, and theorize that both age and proinflammatory or immunomodulating effects of transfused cells may limit efficacy and contribute to increased patient morbidity and mortality. Also controversial is the ability of pre- and post-storage leukoreduction of RBCs to mitigate adverse transfusion-related events. While there are several studies evaluating the transfusion trigger, the RBC storage lesion and transfusion-related immunomodulation in experimental animal models, there is little research pertaining to clinical veterinary patients. RBC transfusion is unequivocally indicated for treatment of anemic hypoxia. However, critical hemoglobin or Hct below which all critically ill patients require transfusion has not been established and there are inherent risks associated with allogenic blood transfusion. Clinical trials designed to evaluate the effects of RBC age and leukoreduction on veterinary patient outcome are warranted. Implementation of evidence-based transfusion guidelines and consideration of alternatives to allogenic blood transfusion are advisable.

Packed Red Blood Cell Transfusion Increases Regional Cerebral and Splanchnic Tissue Oxygen Saturation in Anemic Symptomatic Preterm Infants

Preterm infants often receive multiple packed red blood cell (PRBC) transfusions that are intended to improve tissue oxygen levels. Near-infrared spectroscopy (NIRS) monitors regional cerebral tissue oxygen saturation (CrSO(2)) and splanchnic tissue oxygen saturation (SrSO(2)). Before such technology can be employed in neonatal transfusion management, it must first be established that transfusions result in an increase in tissue oxygen saturation. This prospective, observational study used NIRS to determine if PRBC transfusions increase the CrSO(2) and SrSO(2) of symptomatic anemic premature neonates. CrSO(2) and SrSO(2) values were compared for 20-minute duration immediately before, during, immediately after, and 12 hours after transfusion. As a secondary objective, CrSO(2) and SrSO(2) values were correlated with hemoglobin (Hgb) levels. One-way analysis of variance and Pearson correlation statistical tests were used for analysis. A statistically significant increase in CrSO(2) and SrSO(2) values were observed after transfusion in the 30 subjects included (CrSO(2): 62.8 +/- 1.6, 65.6 +/- 1.7, 68.0 +/- 1.3, 67.6 +/- 1.4, P < 0.001 and SrSO(2): 41.3 +/- 2.2, 46.7 +/- 3.0, 52.1 +/- 2.8, 48.2 +/- 2.5, P < 0.001). No correlation was found between CrSO(2) or SrSO(2) and Hgb values. NIRS identified increases in CrSO(2) and SrSO(2) in preterm neonates after PRBC transfusions and has the potential to become incorporated into neonatal transfusion management paradigms.

Hypoxia Due to Shunts in Pig Lung Treated with O2 and Fluorocarbon-derived Intravascular Microbubbles

Earlier work has shown that experimental conditions calling for improved tissue oxygenation could be assisted by i.v. infusion of a dodecafluoropentane emulsion (DDFPe) forming oxygen-transporting microbubbles. The present work investigated the effect of DDFPe on hypoxia due to experimental shunts in the pig lung. Nineteen O(2) breathing, anesthetized pigs had glass beads administered into the trachea so as to significantly depress arterial oxygen tension (PaO(2)). PaO(2) was recorded for up to 12 hrs while 0.1 ml/kg DDFPe was administered 1-3 times. The animals were divided into two groups based on arterial oxygen saturation (SaO(2)) after shunt induction, combined with oxygen breathing: the "SaO(2) >90% group" (n=6) and the "SaO(2) <90% group" (n=13). In the "SaO(2) <90% group," the PaO(2) increased stepwise with each infusion from 56.6+/-2.9 to 88.6+/-14.6 mmHG (P<or=0.001); improvements lasted about 2 hrs after each infusion. Mixed venous oxygenation also increased with the infusions, e.g. (1(st) infusion) from a PvO(2) of 41.4+/-2.3 to 49.9+/-4.2 mmHg (P<or=0.05) and SvO(2) 58.0+/-2.9% (P<or=0.01), the venous changes supporting arterial oxygenation. At the same time, arterial CO(2) levels fell. Arterial O(2) and CO(2) levels were paralleled by similar changes in muscle tissue. Pulmonary arterial pressures did not indicate any pulmonary embolization by bubbles. Toxic effects of the treatment were not observed. These results suggest that, on condition of successful toxicity testing, intravascular administration of a DDFPe and oxygen breathing may be beneficial in severe right-to-left shunting in humans.

Automated Erythrocytapheresis in Sickle Cell Disease: Impact On Hospital Admission Rate and Iron Loading.

Abstract 1522Poster Board I-545INTRODUCTIONRed cell exchange in sickle cell disease (SCD) reduces the risk of life threatening complications including acute chest syndrome, and thromboembolic stroke. Reduction in Hb S to less than 30% reduces overall blood viscosity and improves tissue oxygenation. With treatment being life-long, concerns over iron loading, patient compliance, blood-bourne infections, and cost could temper its effectiveness.METHODS/SUBJECTSA retrospective study of 74 patients with SCD (mean age 37.5, range 19-73) on automated red cell exchange (mean 21.3 exchanges, range 1-74) was carried out for the period September 1995 to January 2009. Primary end points included the effect of consistency of exchange on hospital admission rate and the relationship between steady state haemoglobin (Hb) and serum ferritin (iron loading). The impact of the consistency of exchange was assessed by dividing the patients into 4 groups. A: Regular exchanges at least every 8 weeks. B: Regular exchanges with occasional short breaks. C: 3 or fewer exchanges per year. D: 4 or fewer exchanges in total. Average hospital admission data per year pre- and post- exchange transfusion programme were calculated. Patients were excluded if no exchanges or hospital admissions had happened in the last 4 years. To assess the relationship between ferritin and steady state Hb, the pre-treatment ferritin, latest ferritin, and steady state Hb were recorded. Patients were excluded if they were on iron chelation. Target post-procedure Hb was 10-11g/dL in all patients, with Hb S % <15%.RESULTSThe 74 subjects received a total of 1578 exchange procedures, with a median of 8.00 units per exchange (range 5-10.5). Median time on erythrocytopheresis was 2.60 years (range 0.0 – 13.0 years). The mean steady state Hb was 10.0g/dL (SD 1.24).Hospital admission data was available for 67/74 (91%) patients. This included 25 in group A, 11 in group B, 5 in group C and 26 in group D. Fourteen patients in group D were excluded due to no record of admissions or exchanges in the last 4 years. In group A, there was a significant reduction in average hospital admission days per year, from 34.8 days/year (range 0-365, SD 71.4) to 7.60 days/year [range 0-34, SD 9.87 (p<0.005)]. In group B and group C, there was a non-significant reduction in average admission days per year from 38.1 days/year (range 1-124, SD 40.98) to 34.1 days/year [range 0-163, SD 55.14 (p=0.53)] and 45.3 days/year (range 0-75, SD 29.8) to 30.4 days/year [range 4-68, SD 24.48 (p=0.08)] respectively. In group D, there was a non-significant increase in admissions from 11.64 days/year (range 0-43, SD 15.33) to 42.26 days/year [range 3-190, SD 65.75 (p=0.161)].A slight increase in mean serum ferritin levels was seen post initiation of an exchange transfusion program (pre 2523μg/L (range 11-15990, SD 3198) to post 2659μg/L [range 21-14229, SD 3229 (p=0.10)]. The data from one patient were excluded from analysis because the patient was on iron chelation. There was a strong negative correlation between serum ferritin levels and the patient's steady state Hb (r= -0.73, see graph A). The line of best fit went through no net ferritin change at the Hb level of 10.5g/dL, the midpoint of the target Hb range. This suggests that the ‘top-up' of patients with a low pre-exchange Hb with extra donor red blood cells (carried out automatically by the exchange machine to get the patient's Hb up to the post-exchange target level) is also increasing the patient's iron loading.CONCLUSIONSReduction in hospital admissions for sickle cell patients on erythrocytopheresis is dependent on a good patient consistency and compliance with treatment schedules. A statistically significant reduction in the average hospital admission days per year is lost when erythrocytapheresis exchanges are further than 8 weeks apart. Iron loading on exchange transfusion correlates to the patient's steady-state Hb, with patients achieving a baseline Hb of less than the target level (10g/dL) increasing their iron load. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute Hemodynamic and Vascular Effects of Transfusion in Chronically Transfused Patients with Sickle Cell Anemia.

Abstract 1516Poster Board I-539 IntroductionPatients with sickle cell anemia (SCA) who are at risk for stroke or develop recurrent episodes of acute chest are often placed on chronic transfusion therapy. The acute hemodynamic and vascular consequences of transfusion are poorly characterized. In order to better characterize chronic changes in these patients, it is important to understand the acute changes involved with this intervention. MethodsWe enrolled SCA patients who are on chronic transfusion therapy in a prospective study to determine the cardiovascular effects of a single transfusion. The patients were older than 10 years of age, received chronic transfusions for greater than one year, and were crisis free for more than four weeks. All patients were studied immediately prior to transfusion and repeated within five days. Brachial artery relaxivity, laser doppler capillary blood flow monitoring, and near infrared spectroscopy of the hand was done in the setting of post occlusive reactive hyperemia. Studies included complete cardiac echocardiogram as well as laboratory markers of hemolysis, iron levels, blood count, viscosity and inflammation were obtained pre and post transfusion. Statistics utilized paired t-tests for paired data and for correlative data t-tests and chi square analysis was used. ResultsThere are 15 patients enrolled in the study with an average age of 18.7yrs. There are 8 females and 7 males with average ages of 20.6 and 16.4 yrs respectively. With transfusion, hemoglobin increased from 9.4 g/dl to 11.6 g/dl post (p<0.0001), reticulocyte count decreased from 12.4% to 7.8% (p=0.0019) and HbS% decreased from 38.2% to 31.5% (p=0.0001). Markers of hemolysis (LDH, Plasma Free Hemoglobin, Arg/Orn Ratio) do not differ significantly pre and post transfusion. Cardiac index decreased from 5.4L/min/m2 to 4.1 L/min/m2 (p=0.0012), resulting from decreased stroke volume (70.8ml to 58.9ml, p=0.0119) and lower heart rate (84 to 78bpm, p=0.0098). Systolic and diastolic function metrics were unchanged, as was estimates of pulmonary artery pressure. Blood pressure was unchanged, indicating that the change in cardiac output was matched by parallel changes in total vascular resistance. Endothelial function and regional vascular reactivity assessed using laser Doppler capillary flow analysis demonstrated no significant change in hyperemic response pre and post transfusion. Blood viscosity increased with transfusion in a shear-rate dependent manner, for low shear rates the viscosity increased an average of 62% using fully oxygenated samples and at higher shear rates the viscosity increased an average of 25% using fully oxygenated samples. DiscussionTransfusion therapy predictably increased oxygen carrying capacity, lowered reticulocyte count and %hemoglobin S. While these changes might improve tissue oxygen delivery, parallel changes in vascular resistance served to maintain relatively constant oxygen delivery. The rise in vascular resistance could result from increased blood viscosity or changes in vascular tone; we are currently conducting studies to try to separate these mechanisms. Despite the 24% reduction in cardiac index, no significant change was observed in microvascular perfusion or its response to forearm occlusion. The vascular system of SCA patients demonstrates chronic endothelial dysfunction but was not acutely influenced by transfusions, consistent with the lack of acute improvement in surrogates for hemolysis or nitric oxide metabolism. Further work is necessary to determine whether transfusion-mediated changes in tissue oxygen delivery vary among different organs and vascular beds. DisclosuresWood:Novartis: Research Funding.

Pentoxifylline in Ischemia-Induced Acute Kidney Injury in Rats

Ischemia is an important cause of acute kidney injury (AKI). Pentoxifylline has been shown to improve tissue oxygenation and endothelial function and inhibit proinflammatory cytokine production. The aim of this study was to evaluate a possible renal protective effect of pentoxifylline against ischemia by measuring mitochondrial respiratory metabolism as an index of cell damage. Rats were submitted to right nephrectomy. The left kidney was submitted to ischemia by clamping the renal artery for 45 minutes. Immediately after release of the clamp, 1 mL of a solution containing 20 mg of pentoxifylline/mL was injected intravenously, while a control group received 1 mL of normal saline intravenously. Five minutes after the injection, the left kidney was removed, homogenized, and subjected to refrigerated differential centrifugation. Mitochondrial respiratory metabolism was measured polarographically. The mitochondria isolated from the kidneys of saline-treated rats had an endogenous respiration of 9.20 ± 1.0 ηmol O2/mg protein/min compared to 8.9 ± 1.4 ηmol O2/mg protein/min in the pentoxifylline-treated rats (p > 0.05). When stimulated by sodium succinate, the respiratory metabolism increased in a similar fashion in both groups of animals: 17.9 ± 2.3 and 18.1 ± 2.1ηmol O2/mg protein/min in the untreated and pentoxifylline-treated groups, respectively (p > 0.05). In the present study, pentoxifylline was not found to exert any protective effect on the kidney. It is possible that at the time of pentoxifylline administration, the mitochondria had already been damaged by the process of ischemia, and its effect may have been insufficient to reverse cell damage.

Effect of trans sodium crocetinate on brain tumor oxgenation

Glioblastoma multiforme tumors typically exhibit regions of hypoxia. Hypoxic regions within the tumor make cells less sensitive to radiosurgery and radiation therapy. Trans sodium crocetinate (TSC) has been shown to be a radiosensitizer. The goal of this research was to elucidate the underlying mechanism of TSC's radiosensitizing effect. A rat C6 glioma model was used. The C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Two weeks later, MR imaging was used to confirm the presence of a glioma. Following demonstration on MR imaging of a brain tumor, animals were randomized into 1 of 2 groups: 1) TSC alone (100 microg/kg), or 2) saline control. Licox probes were inserted into the brain tumor and contralateral cerebral hemisphere. Tissue oxygenation measurements were recorded before and after intravenous infusion of either TSC or saline. Not surprisingly, tissue oxygenation measurements revealed that the brain tumor was hypoxic relative to the contralateral cerebral hemisphere brain tissue. Two to 8 minutes after TSC was infused, tissue oxygenation measurements in the brain tumor increased above baseline by as much as 60%. After this temporary elevation following TSC infusion, tumor oxygenation measurements returned to baseline. No significant elevations in tissue oxygenation were seen on the contralateral side. Similarly, the saline vehicle was not observed to increase tissue oxygenation in either the brain tumor or the contralateral brain tissue. Administration of TSC transiently improves tissue oxygenation in hypoxic gliomas. Such an effect is one potential mechanism for the radiosensitization previously observed after addition of TSC.

The use of early intervention to prevent postoperative complications

The incidence of complications following major surgery is surprisingly high. Patients who develop complications suffer a reduction in long-term survival. This review aims to explore recent advances in the management of surgical patients aimed at preventing postoperative complications. Identifying patients prior to surgery who are at risk of a poor outcome remains challenging. There are a number of scoring systems to assist clinical risk assessment. Recent work has investigated the use of plasma biomarkers for perioperative risk prediction. Therapies aimed at reducing complication rates by attempting to improve tissue oxygen delivery include goal-directed haemodynamic therapy and postoperative noninvasive ventilation. The role of perioperative beta-adrenoceptor antagonists remains unclear. Other important measures include the use of a surgical safety checklist and thromboprophylaxis. Current systems for the identification and treatment of high-risk surgical patients are inadequate. Further research is required to establish the optimal approach to the identification and management of the high-risk surgical patient.

ERYTHROPOIETIN ENHANCES OXYGENATION IN CRITICALLY PERFUSED TISSUE THROUGH MODULATION OF NITRIC OXIDE SYNTHASE

The aim of this study was to investigate the effect of human recombinant erythropoietin (EPO) on the microcirculation and oxygenation of critically ischemic tissue and to elucidate the role of endothelial NO synthase in EPO-mediated tissue protection. Island flaps were dissected from the back skin of anesthetized male Syrian golden hamsters including a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. Before ischemia, animals received an injection of epoetin beta at a dose of 5,000 U/kg body weight with (n = 7) or without (n = 7) blocking NO synthase by 30 mg/kg body weight L-NAME (Nomega-nitro-L-arginine methyl ester hydrochloride). Saline-treated animals served as control (n = 7). Ischemic tissue damage was characterized by severe hypoperfusion and inflammation, hypoxia, and accumulation of apoptotic cell nuclei after 5 h of collateralization. Erythropoietin pretreatment increased arteriolar and venular blood flow by 33% and 37%, respectively (P < 0.05), and attenuated leukocytic inflammation by approximately 75% (P < 0.05). Furthermore, partial tissue oxygen tension in the ischemic tissue increased from 8.2 to 15.8 mmHg (P < 0.05), which was paralleled by a 21% increased density of patent capillaries (P < 0.05) and a 50% reduced apoptotic cell count (P < 0.05). The improved microcirculation and oxygenation were associated with a 2.2-fold (P < 0.05) increase of endothelial NO synthase protein expression. Of interest, L-NAME completely abolished all the beneficial effects of EPO pretreatment. Our study demonstrates that, in critically ischemic and hypoxic collateralized tissue, EPO pretreatment improves tissue perfusion and oxygenation in vivo. This effect may be attributed to NO-dependent vasodilative effects and anti-inflammatory actions on the altered vascular endothelium.

Hypoxia-inducible factor-1α has a key role in hypoxic preconditioning

Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1α (HIF-1α) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1α gene targets in the brain using neural cell-specific HIF-1α-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO 2) of brain tissue and gene expression were measured during hypoxia. HP improved the pO 2 of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1α and inducible nitric oxide synthase.

Evaluation of Hyperviscous Fluid Resuscitation in a Canine Model of Hemorrhagic Shock: A Randomized, Controlled Study

Enhancing plasma viscosity during fluid resuscitation results in vasodilation and improved microvascular perfusion in rodents subjected to hemorrhagic shock. We hypothesized that resuscitation with hyperviscous lactated Ringer's solution (hyperLRS) would result in improved tissue oxygenation and acid-base values in hemorrhaged dogs. Twelve dogs were anesthetized and splenectomized. Vascular catheterization was performed, and tissue oxygen probes were placed in the jejunal serosa and skeletal muscle to assess macro- and microhemodynamic parameters. Baseline (BL) and posthemorrhage data were obtained. After 1 hour of hemorrhagic shock (mean arterial pressure [MAP] 30-40 mm Hg), treatment groups (n = 6) were administered bolus LRS or hyperLRS, and then received sufficient LRS to achieve and maintain an MAP between 60 mm Hg and 70 mm Hg. Data were obtained at 10, 30, 60, 120, and 180 minutes after fluid resuscitation. There were no significant differences between LRS or hyperLRS groups at BL or posthemorrhage. Blood and plasma viscosity were significantly increased by the administration of hyperLRS at all time points postresuscitation compared with LRS. Significantly more fluid was required to maintain MAP, and vascular hindrance was consistently lower in dogs administered hyperLRS versus LRS, suggesting viscosity-induced vasodilation. Central and mesenteric venous oxygen saturations were significantly decreased, whereas lactate and oxygen extraction ratios were significantly increased after hyperLRS administration compared with LRS. The tissue oxygen tension was similar in dogs administered hyperLRS or LRS. A hyperviscous balanced electrolyte solution did not improve hemodynamic parameters, tissue oxygen tension, or acid-base values despite evidence for viscosity-induced vasodilation.

Goal-directed Perioperative Fluid Management

Goal-directed Perioperative Fluid Management