Oxygen transport dynamics of acellular hemoglobin solutions in an isovolemic hemodilution model in swine.

BACKGROUND: One of the perceived advantages of a hemoglobin-based blood substitute is the provision of oxygen-carrying capacity. Although the hemodynamic response to the infusion of acellular hemoglobin solutions has been extensively studied, less is known about the oxygen transport dynamics of such solutions. We hypothesized that acellular hemoglobin solutions are useful oxygen carriers in anemic states and that higher P50 solutions transport O2 more efficiently than low P50 solutions. We sought to quantify O2 transport dynamics of hemoglobin solutions in an isovolemic hemodilution model in swine. METHODS: Eighteen swine were anesthetized, ventilated, and instrumented for hemodynamic measurements and for withdrawal of arterial and mixed venous blood. The swine were randomized into three groups and progressively bled from an initial hematocrit (Hct) of 30% to Hcts of 19%, 13%, and 8% using isovolemic exchange with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP, n = 6); an identical hemoglobin solution without the pyridoxalation, resulting in a low P50 solution (POE-Hb, n = 6); or an osmotically similar control solution of pentastarch (PS, n = 6). Hemodynamic measurements, arterial and mixed venous O2 content, and O2 extraction ratio (ER), were determined in whole blood (WB), the red blood cell (RBC) phase, and the plasma phase utilizing a compartmentalized approach. RESULTS: Mean pulmonary arterial pressure was higher with hemodilution in the PHP and POE-Hb groups than in the PS group (p < 0.05). Cardiac index increased with hemodilution in all groups, but was significantly less than the cardiac index in the PS group at Hcts = 19% and 13%. Oxygen delivery and consumption were maintained at all hematocrits at baseline levels in the PHP and POE-Hb groups, but O2 delivery was significantly decreased in the PS group at Hct = 8% (p < 0.05 for PS vs. baseline and p < 0.05 for PHP and POE-Hb vs. PS). Oxygen extraction ratio increased with progressive hemodilution in both the RBC hemoglobin and plasma phases to a maximum of 39% for PHP and 36% for POE-Hb at Hct = 8%. The percent contribution from the plasma phase to total oxygen delivery and consumption likewise increased with hemodilution to maximum values of 52.7% (PHP) and 68.2% (POE-Hb) for delivery and 40.9% (PHP) and 39.3% (POE-Hb) for consumption. CONCLUSION: Acellular hemoglobin solutions provide a significant contribution to O2 delivery and consumption, particularly in severe anemia, in this model of isovolemic exchange. The differences in the P50 of the two hemoglobin solutions do not appear to significantly influence oxygen dynamics over the range of hematocrits studied.

Comparison of the response of saline tonometry and an automated gas tonometry device to a change in CO2.

OBJECTIVE: To examine the speed of response of saline tonometry and an automated gas tonometry system by using standard tonometry catheters. DESIGN: In vitro validation study. SETTING: Experimental research laboratory. INTERVENTIONS: Tonometry catheters were placed in a test chamber designed to simulate the lumen of a hollow viscus and were exposed to a rapid change in CO2 from 0% to 5% or 10%. Measured CO2 over time was fit to a mathematical model to determine the response time constant (the time to reach 63% of the final value) for each system. MEASUREMENTS AND MAIN RESULTS: Response time to a change in CO2 was significantly faster with the automated gas system than with traditional saline tonometry. The mathematical time constant for a 5% change in CO2 in a gas environment was 2.8 mins (95% confidence interval, 2.6-3.0 mins) for the gas and 6.3 mins (95% confidence interval, 5.8-7.3 mins) for the saline technique. These times were longer for the CO2 change in a liquid environment: The time constant was 4.6 mins (95% confidence interval, 4.5-4.7 mins) for the gas system and 7.8 mins (95% confidence interval, 7.15-8.6 mins) for the saline tonometry. There was a significantly lower final equilibration value for the CO2 measurement with saline tonometry. There was essentially no difference in time constants for each system for a 5% change compared with a 10% CO2 change, except for a slightly faster time constant for the gas tonometry system with a 5% change in the gas environment (5%: 2.8 mins vs. 10%: 3.3 mins). CONCLUSIONS: The automated gas tonometry system has a significantly faster response to a change in CO2 than conventional saline tonometry.

Outcome analysis in patients with primary necrotizing fasciitis of the male genitalia.

OBJECTIVES: To characterize patients with primary necrotizing fasciitis of the male genitalia (Fournier's gangrene) and to identify risk factors and prognostic variables of survival. METHODS: Fifty consecutive patients with primary necrotizing fasciitis of the male genitalia treated at our institution during a 15-year period between 1984 and 1998 were retrospectively analyzed. Of these patients, 44 (88.0%) were found to be eligible for analysis of the outcome parameters. Univariate survival analysis was performed using the Kaplan-Meier algorithm followed by multivariate analysis of statistically significant variables. Six patients (12.0%) who were severely immunocompromised were studied separately. RESULTS: Medical comorbidities were prevalent, with diabetes being the most common condition (50%). The overall mortality rate was 20% (10 of 50). Three statistically significant predictors of outcome were identified among the variables analyzed. These were the extent of the infection (P = 0.0262), the depth of the necrotizing infection (P = 0.0107), and treatment with hyperbaric oxygen (P = 0.0115). Multivariate regression analysis of these variables identified the extent of the infection (P = 0.0234) as the only statistically significant, independent predictor of outcome in the presence of other covariables. CONCLUSIONS: The involved body surface area appears to be the most important prognostic variable, with a significant impact on outcome. Given the high mortality of the disease entity and a trend toward the improved survival of patients receiving hyperbaric oxygen, this treatment form appears indicated in more severe cases. Immunocompromised patients, who frequently have an atypical and fulminant clinical course, appear to constitute a separate group with a dismal prognosis.

Comparison of various hemoglobin polyoxyethylene conjugate solutions as resuscitative fluids after hemorrhagic shock.

BACKGROUND: Previous research suggested that splanchnic hypoperfusion occurs after resuscitation with certain acellular hemoglobin solutions. We examined the influence of maltose content and oxygen affinity on resuscitation with various hemoglobin polyoxyethylene conjugate solutions after hemorrhage. METHODS: Fifteen swine underwent hemorrhage and equal volume resuscitation with pyridoxalated hemoglobin polyoxyethylene conjugate containing 0% or 8% maltose, or low P50 conjugate, which also contained 8% maltose. Five control animals were monitored but not bled. Regional blood flow was determined by using radioactive microspheres, gastric mucosal perfusion was estimated with tonometry, and gut histopathology was evaluated. RESULTS: All hemoglobin solutions produced vasoconstriction, manifested by elevated mean systemic and pulmonary artery pressures without a significant decrease in cardiac index compared with the sham group. Resuscitation with maltose-containing solutions elevated arterial and regional PCO2 and depressed arterial pH and gastric pHi (p < 0.05 for all). Splanchnic and renal blood flows were reduced in the low P50 + 8% maltose group (p < 0.05 vs. sham and baseline for renal blood flow), possibly indicating greater regional vasoconstriction in this group. Ileal mucosal damage was more severe in the maltose-containing groups and correlated with decreased pHi. CONCLUSION: Vasoconstriction occurred in all groups but was more severe in the low P50 + 8% maltose group. Maltose-containing solutions caused respiratory acidosis, decreased pHi, and histologic evidence of mucosal injury. Pyridoxalated hemoglobin polyoxyethylene conjugate without maltose was a superior resuscitation solution in this swine model.

Blunt vascular injuries of the head and neck: is heparinization necessary?

BACKGROUND: Blunt vascular injuries to the head and neck (BHVI) represent some of the most devastating and morbid injuries seen by a trauma surgeon. This series reviewed the experience of a single institution to determine if diagnostic and therapeutic guidelines can be established for these uncommon injuries. In particular, the utility of anticoagulation in the treatment of these injuries is examined. METHODS: The institutional trauma registry of a single state-designated Level I trauma center was examined for patients with BHVI. Patients were identified and their charts reviewed individually with regard to multiple data points including the type of injury, its presentation, the treatment of the injury, and the functional outcome of the patient. RESULTS: Twenty-nine BHVI in 23 patients were reviewed from 1989 to 1997. No mortalities were noted. Among the injuries noted were 14 internal carotid artery dissections and 8 carotid artery tears. Thirteen patients had accompanying closed head injuries. Ten patients were diagnosed after an abnormal neurologic examination, and eight others were diagnosed after having carotid canal fractures. Heparin was started within 48 hours of injury in 4 patients (17%) and was used in a total of 12 patients (52%). No patient worsened neurologically after diagnosis independent of the use of heparin. Thirteen patients (57%) had no or minimal deficits upon discharge. CONCLUSION: BHVI represent a serious cause of morbidity in the patient with multiple injuries. Patients with closed head injuries and carotid canal fractures appear most at risk. A multicenter, randomized trial involving antiplatelet therapy, full systemic anticoagulation, or observation with a long-term functional assessment is indicated to determine the optimal management of these injuries.

Effect of alpha(alpha)-cross-linked hemoglobin and pyridoxalated hemoglobin polyoxyethylene conjugate solutions on gastrointestinal regional perfusion in hemorrhagic shock.

BACKGROUND: Hemoglobin-based blood substitutes may cause vasoconstriction, which could limit organ perfusion during trauma resuscitation. We investigated the effect of two hemoglobin solutions on regional blood flow and mucosal perfusion in the gastrointestinal tract in a hemorrhagic shock model. METHODS: Twenty-four swine were bled 30% of blood volume over 1 hour. Six additional animals were anesthetized and monitored but did not undergo hemorrhage. Bled animals were resuscitated with alpha(alpha)-hemoglobin (alpha(alpha)Hb), pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), shed blood, or lactated Ringer's solution. Regional blood flow was measured by radiolabeled microspheres. Gastric mucosal perfusion was estimated by measuring intramucosal pH (pHi) by tonometry. RESULTS: PHP and shed blood restored small-bowel flows to sham values, whereas lactated Ringer's solution and alpha(alpha)Hb did not. Shed blood and PHP, but not alpha(alpha)Hb, restored cardiac index (CI) to baseline (p < 0.05). Mean pulmonary artery pressure was elevated over baseline with alpha(alpha)Hb and PHP and remained elevated with alpha(alpha)Hb (p < 0.05). pHi was significantly lower after resuscitation with PHP than with other fluids. CONCLUSION: PHP was efficacious in restoring CI and small-bowel flow, but the pHi remained low, indicating possible continued mucosal ischemia. Alpha(alpha)Hb led to limited recovery of CI and small-bowel blood flow but restored pHi close to baseline. Shed blood was efficacious in restoration of pHi, gastrointestinal blood flows, and systemic hemodynamics.

Multiple impalement with survival.

An unusual case of multiple impalement by chain-link fence posts is presented in which facial, thoracic, and abdominal injuries were sustained following a rollover motor vehicle crash. Torso impalement injuries are briefly reviewed and guidelines for the management of such injuries are described.

Computer-assisted design of an implantable, intrathoracic artificial lung.

A semiempirical mathematical model of convective oxygen transport is used to design a new, low pressure loss, implantable artificial lung that could be used as a bridge to lung transplantation in patients with advanced respiratory failure. The mass transfer and flow friction relations pertinent to the design of a cross-flow hollow fiber membrane lung are described. The artificial lung is designed to transfer over 200 ml/min of oxygen at blood flow rates up to 5 L/min. A compact design and a blood-side pressure loss of < 15 mm Hg allows the device to be implanted in the left chest without the need for a prosthetic blood pump. Surgical implantation of the artificial lung would require the creation of inflow and outflow anastomoses. Oxygen would be supplied via an external source. Blood properties, operating conditions, and empirically determined mass transfer and flow properties are all specified and input into a computer program that numerically solves the design equations. Computer-generated values for the device frontal area, blood path length, and fiber surface area are thereby obtained. The use of this computer-assisted design minimizes the need for extensive trial-and-error testing of prototype devices. Results from in vitro tests of a prototype implantable lung indicate that the mathematical model we describe is an accurate and useful tool in the design of hollow fiber artificial lungs.

Use of a mathematical model to predict oxygen transfer rates in hollow fiber membrane oxygenators.

A semi-empirical theoretical model of oxygen transfer is used to predict the rates of oxygen transfer to blood in hollow fiber membrane oxygenators over a wide range of inlet conditions. The predicted oxygen transfer rates are based on performance of the devices with water, which is more cost effective and easier to handle than blood for in vitro evaluations. Water experiments were conducted at three different flow rates to evaluate oxygen transfer performance in three commercially available membrane oxygenators. Data obtained from these experiments were used in a computer model to predict the rate of oxygen transfer to bovine blood at specified inlet conditions. Blood experiments were conducted at three different flow rates at a wide variety of inlet conditions, including different pH levels, hemoglobin concentrations, and oxyhemoglobin saturations for the three types of oxygenators. The measured and predicted oxygen transfer rates are closely correlated, which suggests that we have an accurate, reliable method for predicting oxygen transfer in hollow fiber membrane lungs.

Design and evaluation of a new, low pressure loss, implantable artificial lung.

The authors designed and tested an artificial lung intended for intrathoracic implantation as a bridge to lung transplantation in chronic pulmonary insufficiency or as an alternative in the treatment of advanced acute respiratory failure. The prototype devices are comprised of 380 microns outer diameter polypropylene matted fibers with a blood path length of 3.5 cm, frontal area of 128 cm2, void fraction (porosity) of 0.53, and surface area of approximately 2.2 m2. Blood flow is external and approximately perpendicular to the fiber bundle, which fits in an extruded, flexible polyethylene terephthalate housing. Inflow and outflow anastomoses are made to the pulmonary artery and the left atrium, respectively, thereby avoiding a prosthetic blood pump. Inlet and outlet gas lines exit through the chest wall. Nine in vitro experiments of oxygen (O2) transfer performance by the device, with water, initially were done. Our previously described semiempirical mathematical model of convective O2 transfer in cross-flow, hollow fiber membrane lungs was applied to the results from the water tests to predict the transfer rates at any set of blood conditions. Five in vitro blood tests were conducted using a single-pass technique to evaluate O2 and carbon dioxide (CO2) transfer rates, measure pressure losses, and compare predicted and measured O2 transfer rates. O2 transfer rates of 150-200 ml/min, and CO2 transfer rates exceeding 200 ml/min, could be achieved at blood flow rates as great as 4 l/min. Pressure drops of approximately 10-20 mmHg were observed at blood flow rates of 2-4 l/min. Preliminary results of device implantation in two pigs indicate the feasibility of achieving clinically significant O2 and CO2 transfer rates with a low blood-side pressure loss.

Enhanced oxygen delivery induced by perfluorocarbon emulsions in capillary tube oxygenators.

Previous studies showed that a new generation of perfluorocarbon (PFC) emulsions increased tissue PO2 in the cat retina to a degree that could not be explained by the small increase in arterial O2 content seen after the infusion of low doses of 1 g PFC/kg body weight. It seems that increased O2 delivery at the tissue level after PFC infusion is caused by a local effect in the microcirculation. The authors studies this effect in vitro at steady state in a closed loop circuit, consisting of one of two types of capillary tube oxygenators, deoxygenator(s), a reservoir bag filled with anticoagulated bovine blood or saline (control), and a roller pump, to see if the addition of PFC would have an effect on the PO2 difference (delta PO2) across the capillary tube membrane oxygenator at a blood flow rate of 3 l/min. Perfluorocarbon was added in three incremental doses, each giving about 0.7 vol% of PFC. The delta PO2 across the oxygenator was measured before and after each dose. The mean percent increases in delta PO2 in blood for two types of oxygenators were 19.2 +/- 8% (mean +/- SD, n = 6, P = 0.002) and 9.9 +/- 4% (n = 3, P = 0.05), respectively, whereas the mean percent change in delta PO2 in saline was -4.9 +/- 2% (n = 2, P = 0.2). Inlet PO2s to the oxygenator were only minimally increased. The authors conclude that O2 delivery was significantly enhanced after injection of PFC in blood in this capillary tube model. A near wall excess of PFC particles may account for the augmentation of O2 diffusion in this model.