Development of a silicone hollow fiber membrane oxygenator for ECMO application

A new silicone hollow fiber membrane oxygenator for extracorporeal membrane oxygenation (ECMO) was developed using an ultrathin silicone hollow fiber, with a 300 microm outer diameter and a wall thickness of 50 microm. The hollow fibers were mechanically cross-wound on the flow distributor to achieve equal distribution of blood flow without changing the fiber shape. The housing, made of silicone coated acryl, was 236 mm long with an inner diameter of 60 mm. The surface area was 1.0 m2 for prototype 211, and 1.1 m2 for prototype 209. The silicone fiber length was 150 mm, and the silicone membrane packing density was 43% for prototype 211 and 36% for prototype 209. Prototype 211 has a priming volume of 208 ml, and prototype 209 has a priming volume of 228 ml. The prototype 211 oxygenator demonstrates a gas transfer rate of 120 +/- 5 ml/min (mean +/- SD) for O2 and 67 +/- 12 ml/min for CO2 under 2 L of blood flow and 4 L of O2 gas flow. Prototype 209 produced the same values. The blood side pressure drop was low compared with the silicone sheet oxygenator (Avecor, 1500ECMO). These results showed that this new oxygenator for ECMO had efficiency similar to the silicone sheet oxygenator that has a 50% larger surface area. These results suggest that the new generation oxygenator using an ultrathin silicone hollow fiber possesses sufficient gas transfer performance for long-term extracorporeal lung support.     

New design for a pumping artificial lung

A new prototype of a pumping artificial lung (PAL) has been designed and tested. The device performs the functions of both the pump and oxygenator components of an extracorporeal perfusion circuit. Previous prototypes that the authors developed (Type A) had gas exchanging microporous fibers formed into propeller-like vanes that, upon rotation, pump the blood. The design of the new PAL prototypes (Type B) uses the rotation of an annular bank of fibers to drive flow. The fiber bank, including sealed gas manifolds, lies within the housing of a modified Bio-Medicus BMP-50 pump head (Bio-Medicus, Eden Prairie, MN). Rotation of the fiber bank is driven through a magnetic coupling. Inlet and outlet gas lines enter the pump head through a sealed bearing. The Type A PAL suffered from insufficient pumping rates and gas exchange, necessitating redesign. The authors have constructed two PAL-B prototypes with a priming volume of only 140 ml and gas exchange surface areas of 0.16 and 0.60 m2. During in vitro saline testing, these prototypes showed significant pump performance, pumping 7.0 L/min against zero head at 3,500 rpm. The larger prototype had exchange rates in saline of up to 71 ml O2/min and 75 ml CO2/min. Gas exchange fluxes (O2 = 119 ml/[min.m2] and CO2 = 125 ml/[min.m2]) for the PAL-B are significantly higher than that of commercially available oxygenators in saline. Future prototypes will have increased surface area and fibers smaller than the 0.038 cm outside diameter fibers used in the present prototypes. A primary concern in using microporous fibers to push the blood was the durability of the fibers at high pump speeds. High speeds exhibited no negative effects on gas exchange abilities or fiber durability.     

Membrane versus bubble oxygenator in hyperthermic regional perfusion: a prospective randomized clinical study

In a prospective randomized clinical study a routinely used bubble oxygenator (Bentley-5) was compared with a hollow fiber membrane oxygenator (D 701 Masterflo 34) during hyperthermic isolated extremity perfusion. This was done to find out whether there were differences between the two oxygenators in hemolysis, cellular damage, oxygenation and temperature achieved during extremity perfusion. In 30 perfusions blood samples were obtained at defined times: plasma hemoglobin (Hb), serum lactate dehydrogenase (s-LDH), number of erythrocytes, mean corpuscular volume (MCV), hemoglobin and bilirubin were determined for hemolysis, leukocyte count (neutrophils, lymphocytes, monocytes) and platelets as a check for cellular damage, and PO2, PCO2, O2 saturation and pH to define blood oxygenation and CO2 elimination. Maximal increase in temperature after 30 min and perfusion time until maximum tissue temperature were also recorded. The membrane oxygenator yielded better results from the aspect of hemolysis: s-LDH and plasma Hb were significantly different (p < 0.001). Cellular damage was less with the membrane oxygenator: platelet differences were significant (p < 0.01). Oxygenation and hyperthermia were obtained more quickly and were better controllable in membrane oxygenator. Further advantages for the patient were the smaller volume of blood needed for priming in a membrane oxygenator (750 vs. 1,200 ml) and improved safety resulting from a 'closed' perfusion system. On the basis of the clinical prospective randomized trial conducted, we conclude that membrane oxygenators must be adopted as the new standard in isolated hyperthermic extremity perfusion.     

Reusable tubular membrane oxygenator for isolated organ hemoperfusion

A reusable tubular membrane oxygenator is described for hypotraumatic hemoperfusion of isolated organs in physiological studies. The constructed oxygenator was of approximately 0.24-m2 effective surface area and contained 450 silicone rubber capillaries of 0.51-mm nominal ID, 34.9 cm long, fixed by conical-shaped, plastic blood headers at manifolds made from Dow-Corning MDX-4-4210 silicone elastomer. During ex vivo hemoperfusions in dogs at inlet hemoglobin saturations near 67%, oxygen transfer rates of the oxygenator increased serially, from 16.6 +/- 1.7 ml/min per m2 (mean +/- SD) at blood flows of 100 ml/min to 34.1 +/- 3.8 ml/min per m2 at flows of 500 ml/min. The oxygenator was thromboresistant and of much loss priming blood volume and wall compliance than the nonresuable Travenol membrane oxygenator of 0.26-m2 effective surface area. The tubular oxygenator was easily cleaned and reassembled, with reproducible oxygen transfer rates. It should prove useful for hemoperfusion studies in organs of moderate size, such as the isolated canine kidney, stomach, and pancreas.     

Nitric oxide prevents human platelet adhesion to fiber membranes in whole blood

During cardiopulmonary bypass or long-term extracorporeal life support, foreign surface induced platelet deposition in the oxygenator causes deterioration of gas exchange. In this study, the authors evaluated the effectiveness of nitric oxide (NO) in reducing the adhesion of platelets in whole blood to the surface of hollow fiber membranes. For this purpose, a test chamber was designed consisting of a gas exchanger with ten mitsubishi multi-layered composite hollow fibers (MHF: 257 mm OD; 203 mm ID; 70 mm length) and a polypropylene tube (16 mm OD; 100 mm length). Pure N2 (control) or nitric oxide (NO) (100 ppm, 200 ppm in N2) were delivered into the test chamber previously filled with 13 ml human whole blood. Platelet counts and platelet factor 4 (PF4), as a measure of platelet activation, were measured before and after either 1 or 2 hr of testing, and fibers were observed under scanning electron microscopic study (SEM) after each experiment. In the control and 100 ppm NO groups, platelet counts decreased and the level of PF4 increased during the 1 hr period. In the 200 ppm NO group, almost no platelet deposition could be observed on the surface of fibers under SEM. In conclusion, NO flow through hollow fiber membranes can markedly reduce platelet adhesion. Additional quantitative studies should define the optimal concentration for this effect and determine if this finding could improve oxygenator function, especially under conditions of long-term support.     

Evaluation of an extracorporeal membrane oxygenation system using a nonporous membrane oxygenator and a new method for heparin coating

A new heparin binding method was applied to a miniature extracorporeal membrane oxygenation (ECMO) system with a nonporous membrane oxygenator (the priming volume, 45 mL; the membrane surface area, 0.4 m2; maximal flow rate, 2 L/min) that is resistant to plasma leakage. The authors evaluated the stability of the immobilized heparin in vitro and the feasibility of this system in animals. Samples of hollow fibers and tubing were rinsed at 40 degrees C for 4 days in normal saline, Ringer's lactate, and 1 mol/L NaCl solution. Heparin activities on hollow fibers after rinsing were 99 +/- 2.3% (mean +/- SD), 96 +/- 3.9%, and 93 +/- 2.0% of the control in each solution, while those of the tubing were 87 +/- 4.1%, 86 +/- 3.1%, and 76 +/- 8.6%, respectively. Veno-arterial ECMO using this heparin-coated system was performed on five beagles (8 to 12 kg) for 10 hours. Neither major thrombus formation nor plasma leakage was detected during the procedure in spite of a low flow rate (300 mL/min) and a reduced activated clotting time (mean, 128 seconds). Platelets decreased to 52% of the control (P < .01) at 1 hour, but no progressive decrease was seen thereafter. Antithrombin-III decreased (P < .01) and thrombin/antithrombin III complex increased (P < .05 at 4 hours and P < .01 at 6, 8, and 10 hours) during bypass, but the changes of fibrinogen and fibrinopeptide A were not significant. Fibrinogen/fibrin degeneration products, fibrinopeptide B beta 15-42, and plasma-free hemoglobin levels did not rise significantly. O2 transfer of the oxygenators at a flow rate of 300 mL/min were 12.3 +/- 0.4 mL/min at 30 minutes, 14.3 +/- 1.2 mL/min at 5 hours, and 14.7 +/- 1.7 mL/min at 10 hours (no statistical difference). Histological examination of the brains and the kidneys showed no evidence of thromboembolic sequela in any of the animals. These results suggest that this new system is a promising device for long-term ECMO in which the amount of systemic heparinization can be reduced with the minimal possibility of plasma leakage.     

Use of in vitro models of haemofiltration and haemodiafiltration to estimate dosage regimens for critically ill patients prescribed cefpirome

Membrane oxygenators have now gained wide acceptance. A new hollow-fibre membrane oxygenator, the Dideco D903 Avant 1.7, with an optimized membrane surface (1.7 m2) and a wavy blood flow pattern, was tested for gas transfer and blood path resistance in a standardized setting with surviving animals. Three calves (mean body weight 63.29 +/- 2.9 kg) were connected to cardiopulmonary bypass by jugular venous and carotid arterial cannulation, classic roller pump and the Dideco D903 oxygenator with a mean flow rate of 53 +/- 0.1 ml/kg/min for 6 h. After this time, the animals were weaned from the CPB and thereafter from the ventilator. After 7 days, the animals were killed electively. Blood gas analysis was performed before bypass, after mixing (10 min) and then hourly for the 6 h of perfusion. Further samples were taken 30 min (spontaneous breathing) and 60 min after bypass (extubated). Physiological blood gas values could be maintained throughout perfusion in all animals. Mean arterial oxygen saturation varied between 99.3% and 99.7% for the arterial side of the oxygenator compared to 64.6% and 71% for the venous side. The highest mean pressure drop through the oxygenator was 54 mmHg. Postbypass blood gas analysis showed physiological values and no evidence of major lung trauma or pulmonary oedema in relation to the 6 h perfusion. The hollow-fibre membrane oxygenator, Dideco D903, offers excellent gas exchange capabilities and a low pressure drop under experimental conditions, despite reduced membrane surface area. The post mortem examination did not show any deleterious lesion.     

Assay of DNA content and estrogen receptor status in human breast cancer

IVOX was named as an acronym for intravascular oxygenator. The device does not need a blood pomp like an extracorporeal membrane oxygenator (ECMO), and performs intracorporeal gas exchange to be a small elongated, hollow fiber membrane oxygenator designed to lie within the subject's venae cavae so that circulating venous blood can flow freely over and around the external surfaces of the hollow fibers. The amount of gas exchange in IVOX is less than ECMO, however, the equipment is simple and there is no effect to hemodynamics and body temperature. IVOX has been utilized in the management of 165 clinical trials patients in 31 international critical care centers. Currently the gas transfer rate by means of the IVOX device constitutes 1/4 to 1/3 the total metabolic requirement of adult acute respiratory failure patients. Therefore, intentional hypoventilation to limit airway pressures (mild permissive hypercapnia) is recommended to improve CO2 removal with increasing mixed venous CO2 concentrations. In the future, improvements of design, function, and methods of utilization of IVOX device are expected to increase the amount of gas exchange and to enlarge the indications for its use.     

Encapsulation of OKT3 cells in hollow fibers

Encapsulation of an OKT3 cell line in hollow fibers was evaluated in vitro and in vivo. The cell line is a mouse hybridoma producing immunoglobulin G2a (IgG2a) against CD3 human T lymphocytes and thus may function as a nonspecific activation system of a subpopulation of human T lymphocytes. For encapsulation purpose, hollow fibers of polypropylene K600 PP Accurel (Akzo, Germany) were selected. Hollow fibers were siliconized to improve membrane biocompatibility for in vivo experiments. The siliconized hollow fibers exhibited acceptable diffusive permeability (P) [ml/min/m2] for small solutes (for creatinine, p = 63.9 +/- 2.0, n = 3) and larger solutes (for albumin, p = 16.9 +/- 1.9, n = 3; for IgG, p = 1.0 +/- 0.2, n = 3). The 12 cm long hollow fibers were filled with a suspension of OKT3 cells of an average density of 10(6) cells/ ml, and both ends were sealed. The encapsulated cells were cultivated in RPMI 1640/10% CS medium at 37 degrees C, 5% CO2 for a period of 3 to 4 days. After the culture period, the medium was tested on human peripheral blood lymphocytes for the presence of anti-CD3 antibody and read in a flow FACS-trac cytometer (Becton Dickinson Immunocytochemistry Systems, San Diego, CA). The tightness of hollow fiber sealing was tested with a bubble point method. The number of cells increased after cultivation by four- to nine-fold on average (n = 11). Ten experiments were performed in vivo with OKT3 cells encapsulated in hollow fibers and implanted subcutaneously into mice for 3 days. In 50% of the experiments, some anti-CD3 antigens on human lymphocytes were found; however, the difference, in comparison with control, in percent of CD3+ was insignificant. In conclusion, the hollow fiber method for cultivation of hybridoma cells in vitro allows for separation of cells from the medium containing secreted anti-CD3 antibodies and is effective in maintaining cell viability. In vivo application needs additional study.     

A method to obtain a well-defined fraction of respirable para-aramid fibers

We developed a preparation method to obtain respirable-sized fractions of para-aramid fibers. The procedure, based on floatability, consists of stirring and subsequent settling of p-aramid pulp in distilled water. Two distinct phases are obtained, with small fibers in the upper part of the suspension, which represents about 33% of the total volume. Optimal results were obtained when 2.0 g pulp was stirred for 15 hr in 800 ml distilled water containing 0.125% ethanol and settled for 5 hr. The mass yield ranged between 0.4 and 0.6%, more than 90% of the particles had an aspect ratio > or = 3:1. The mean fiber length was about 6 microns, and the mean fiber diameter was about 0.4 microns as determined by transmission and scanning electron microscopy. The number of fibers obtained was 4 x 10(6) fibers/micrograms under our standard conditions.     

Platelet and neutrophil distributions in pump oxygenator circuits. III. Influence of nitric oxide gas infusion

The authors used quantitative gamma scintigraphy to evaluate the influence of nitric oxide gas on platelet and neutrophil deposition in Cobe Duo microporous oxygenators during cardiopulmonary bypass (CPB). The effects of nitric oxide gas on circulating platelet and neutrophil counts and platelet function also were assessed. Animals were prepared by standard methods. Cells were harvested, labeled (111 In platelet and 99mTc neutrophil), infused, and recirculated. Nitric oxide gas, a guanylate cyclase pathway promoter, was infused int he Duo gas port at 500 ppm (t = 0-60 min), increased to 1,000 (t = 60-80 min), and stopped (final, 10 min). Images were taken at 10-15 min intervals during CPB. Standard isotope image corrections were made. No differences between nitric oxide gas and control experiments were observed for flow, pressure, hematocrit, or replacement volume. Nitric oxide gas infusion significantly (p < 0.05) reduced both platelet adherence to the oxygenator and in vitro platelet aggregation. Neutrophil adhesion tended to be lower, and circulating platelet and neutrophil counts tended to be higher with nitric oxide gas infusion. Results of in vitro aggregometry studies using rabbit platelets indicate that the class V phosphodiesterase inhibitor zaprinast can strongly enhance the inhibitory effects of nitric oxide. The authors conclude nitric oxide gas is a promising platelet sparing agent in the setting of CPB.     

Effects of blood flow pulse frequency on mass transfer efficiency of a commercial hollow fibre oxygenator

The clinical advantages achievable through pulsatile blood perfusion during cardio-pulmonary bypass have recently suggested the design of new pulsatile systems for extracorporeal circulation. Still it is not clear whether current commercial membrane oxygenators could be adopted with such systems, since their behaviour with pulsatile perfusion has not been satisfactorily documented yet. In a previous paper, we assessed that pulsatile perfusion of a widely used hollow fibre oxygenator (Sorin Monolyth) at 60 bpm provides more time-consistent oxygen transfer than steady perfusion. The present work is aimed to evaluate how the pulse frequency influences the gas transfer performance of the same device. The oxygenator was subjected to in vitro trials using a roller pump with pulsatile module (Stockert Instrumente) to generate pulsed flow. Four different pulse frequencies (45, 60, 75 and 90 bpm) were investigated at a fixed blood flow rate (4.0 l/min). The experiments lasting six hours were carried out using bovine blood with inlet conditions according to AAMI standards requirements. Blood samples were withdrawn every hour and O2 and CO2 transfer rates were evaluated. The experimental findings confirm that with pulsatile blood flow no time decay take place during prolonged perfusion. Moreover, when pulse frequency increases, transition levels occur for both O2 and CO2. Over these thresholds gas transfer rates display significant increases (p < 0.05), though of little magnitude (up to 2.5% for oxygen over 60 bpm; up to 3.7% for carbon dioxide over 75 bpm).     

Study about development of extracapillary blood flow type oxygenator--comparison with HF-4000, Capiox II, and Silox]

Results about comparison of new extracapillary blood flow type polypropylene hollow fiber oxygenator (PHO) with HF-4000, Capiox II and Silox for effects on blood components, hemolysis, immunoglobulin and high molecular weight proteins, such as complements: 1) Platelet protection was about equal. Silox was best in leucocyte protection. 2) PHO was superior to HF-4000. The extracapillary type was better for hemolysis. 3) Silox was best in immunoglobulin protection. Effect on C3 and C4 was equal, and Silox was best in protection of CH50. Slight differences were caused by silicone membrane, not caused by blood flow type. 4) PHO was superior to HF-4000 (commercial extracapillary type), and almost equal to Capiox II (intracapillary type).     

Acute in vivo studies of the Pittsburgh intravenous membrane oxygenator

The efficacy of an innovative intravenous membrane oxygenator (IMO) was tested acutely (6-8 hrs) in seven calves. The IMO prototypes consisted of a central polyurethane balloon within a bundle of hollow fibers with a membrane surface area of 0.14 m2. The IMO devices were inserted through the external jugular vein into the inferior vena cava of anesthetized calves (68.9 +/- 2.3 kg). Rhythmic balloon pulsation (60-120 bpm) was controlled with an intra-aortic balloon pump console. Oxygen sweep gas was delivered through the device at 3.0 L/min. Gas concentrations were monitored continuously by mass spectroscopy. The principal results were as follows: 1) oxygen and carbon dioxide exchange ranged from 125 to 150 ml/min/m2 and 150 to 200 ml/min/m2, respectively; 2) there was at least a 30-50% augmentation of gas exchange with balloon pulsation; 3) maximum exchange occurred with 60-90 bpm balloon pulsations; and 4) hemodynamic parameters remained unchanged. There were no device related complications, and the feasibility of insertion of the device by a cervical cut-down was established. These acute in vivo experiments show that the Pittsburgh IMO device can exchange oxygen and carbon dioxide gases in vivo at levels consistent with this current prototype design, and that intravenous balloon pulsation significantly enhances gas exchange without causing any end-organ damage.     

A new blood compatible and permselective hollow fiber membrane for hemodialysis

The authors have prepared a blood compatible and highly permselective hemodialysis membrane composed of polyether segmented nylon. This block copolymer was synthesized by polycondensation of bis-3-aminopropyl-poly(tetramethylene oxide) (PTMO) and poly(imino-1,3-bismethyl-cyclohexyl-iminoisophtharoyl) (NyBl) prepolymer obtained by polycondensation of 1,3-bis(aminomethyl)cyclohexane (B) and isophthalic acid (I). The molecular weight (MW) calculated from the number of end-groups was 16,000-21,000. In vitro blood compatibility was evaluated in terms of platelet adhesion onto the surface. PTMO-NyBl surfaces showed excellent platelet adhesion preventing properties. The PTMO-NyBl hollow fiber membrane was obtained by a dry-wet spinning process. The membranes had higher permeability coefficients for macromolecules ranging from MW 10,000 to 20,000 than polysulfone hollow fiber membrane (PS membrane), and had acceptably low albumin permeability for use as a dialysis membrane. The ex vivo blood compatibilities of PTMO-NyBl membrane and PS membrane were investigated by extracorporeal circulation in a pig model. The PTMO-NyBl membrane gave excellent results when assessing hemodialysis leukopenia, oxidative burst, and free platelet count decrease.     

Inter-laboratory comparison of measuring concentration of asbestos fibers less than 5 microM in length using phase-contrast microscopy

Airborne asbestos fibers at the workplace are usually measured by phase-contrast microscopy (PCM), using the membrane filter method (MFM). Although the MFM has an international standardization, the application of this method can lead to wide differences in results. An inter-laboratory study, involving 19 laboratories, was organized. Two fiber classes were counted: 1) fibers greater than 5 microns in length and less than 3 microns in diameter; 2) fibers less than 5 microns in length and less than 3 microns in diameter. The results of each laboratory were normalised to the mean and their counting performance was compared. The estimated coefficients of variation or relative standard deviation (CV) of the normalised results were fitted assuming a constant component (K) and a component depending on the fiber count (Poisson component: mu-1/2). Fitting showed that the constant K is about 0.36 for counting fibers greater than 5 microns in length and about 0.52 for counting fibers less than 5 microns long. It was shown that counting the latter fiber class is influenced primarily by subjective laboratory-to-laboratory differences.     

Technical considerations in the use of the membrane oxygenator (Lande'-Edwards) for open heart surgery

Experience has shown that successful cardio-pulmonary bypass depends upon an efficient oxygenator which causes minimum blood damage. Experience with 1,600 Lande'-Edwards membrane oxygenators in more than 1,000 patients has led to the development of a simple and safe routine for their use in open heart surgery. The circuitry, method of preparation for perfusion, and management of perfusion are described in detail.     

A baboon model for hematologic studies of cardiopulmonary bypass

Objective investigation of new inhibitors of blood protein or cellular systems that are activated during cardiopulmonary bypass (CPB) is impeded by the absence of a satisfactory animal model. Because most baboon hematologic proteins immunologically cross-react with those used for human assays, we developed a robust, reusable baboon model of CPB. Blood samples were obtained from adult baboons at six time intervals before, during, and after 60 minutes of partial CPB at 37 degrees C with peripheral cannulas. Both membrane (n = 7) and bubble oxygenators (n = 7) were investigated. We measured platelet and white blood cell counts; platelet response to adenosine diphosphate and release of beta-thromboglobulin; fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, D-dimer, and plasmin-antiplasmin complex; activated complement (C3b/c and C4b/c); elastase-alpha1 proteinase inhibitor complex; and bleeding times. Adherent glycoprotein IIIa antigen in Triton X-100 washes of the perfusion circuit was also measured. Markers of baboon platelet, complement, and neutrophil activation and thrombosis significantly increased during CPB with bubble oxygenator systems but did not change appreciably in membrane oxygenator circuits. Markers of fibrinolysis, D-dimer, and plasmin-antiplasmin complex did not change with either oxygenator. The baboon model of CPB, when a bubble oxygenator is used, is a robust, reusable animal model for evaluating inhibitors of platelet, complement, and neutrophil activation and thrombosis during and after CPB.     

Reversal of anticoagulation without protamine using a heparin removal device after cardiopulmonary bypass

Protamine sulfate is routinely administered after cardiopulmonary bypass to reverse systemic heparinization, but may cause a severe hypotensive reaction in as many as 2% of patients. Research Medical, Inc., has developed an extracorporeal venovenous heparin removal device (HRD) for use in patients at high risk for a protamine reaction. Circulation through the HRD removes heparin by hollow fiber plasma separation and selective sorption of anionically charged heparin to a polycationically charged poly-L-lysine ligand coupled to a agarose substrate. The heparin depleted plasma then reenters the whole blood pathway and is returned to the patient through the double lumen catheter in the right atrium. To evaluate the HRD in a clinically relevant model, cardiopulmonary bypass was performed in pigs using RA-Ao cardiopulmonary bypass (120 min) with systemic heparinization (300 IU/kg), a nonpulsatile pump with a membrane oxygenator, and systemic hypothermia (28 degrees C). Group 1 (HEP n = 7) had no intervention to neutralize the heparin; Group 2 (HRD n = 7) used the HRD. After 19.7 +/- 4.2 min of circulation through the HRD, the activated clotting time had returned to baseline, whereas the pigs in the HEP group were still anticoagulated (activated clotting time = 396 +/- 152 sec; time to baseline was 124 +/- 9 min). There were no significant differences between groups with respect to hemodynamics, hematocrit levels, leukocyte profiles, or platelet counts, HRD is an effective heparin removal device in a pig model of cardiopulmonary bypass and awaits a phase I clinical trial in humans.     

Identification of human and mouse GP-1, a putative member of a novel G-protein family

OBJECTIVES: To determine a) if serum morphine concentration changes during the first 3 hrs of extracorporeal membrane oxygenation (ECMO); and b) if absorption of morphine onto the membrane oxygenator is responsible for these changes. Also, morphine clearance during the first 5 days of ECMO was studied. DESIGN: Prospective, open-label study with consecutive patient enrollment. SETTING: Neonatal intensive care unit at a university-affiliated, children's hospital. SUBJECTS: Eleven neonates with severe persistent pulmonary hypertension of the newborn receiving continuous intravenous infusions of morphine sulfate and requiring ECMO. INTERVENTIONS: Blood samples were obtained from the subjects and ECMO circuits at predetermined time intervals. MEASUREMENTS AND MAIN RESULTS: Serum morphine concentration was determined using high-performance liquid chromatography. Morphine concentrations were no different from baseline at 5 mins, 1 hr, or 3 hrs after beginning ECMO. There was no significant difference in morphine concentration from samples taken immediately proximal and distal to the membrane oxygenator at 5 mins, 1 hr, and 3 hrs after the start of ECMO. Morphine clearance was calculated on days 1, 3, and 5 of ECMO. The mean value for morphine clearance was 11.7 +/- 9.3 (SD) ml/min/kg (range 2.6 to 34.5). CONCLUSIONS: The initiation of ECMO does not lead to a significant decrease in serum morphine concentration and there is no uptake of morphine onto the membrane oxygenator of the ECMO circuit. Morphine clearance for infants receiving ECMO is variable.