Precise control of nitric oxide concentration in the inspired gas of continuous flow respiratory devices.

Inhaled NO has become widely used for diagnosis and therapy of pulmonary hypertension. The potential hazards of NO inhalation include the formation of methemoglobin, formation of NO2, and generation of free radicals in the presence of humidity and oxygen. Careful monitoring of NO and NO2 concentration, and titration of the dose according to a patient's clinical response is essential to minimize toxicity. This paper describes a formula and method that permits calculation and precise control of NO concentration in the inspired gas. The accuracy of the delivery system was assessed by a comparison of calculated and measured NO and NO2 concentrations in a continuous flow ventilator circuit. A comparison of electrochemical detector (ECD) versus chemiluminescence detector (CLD) monitoring techniques showed agreement between the instruments within approximately 2 ppm, with the ECD averaging a higher reading than the calculated or CLD measured values. We deemed a 2 ppm discrepancy between instruments clinically acceptable, and concluded that the instruments could be used interchangeably for clinical purposes to measure NO1 and that the ECD was preferable to CLD for measuring NO2. Details about the equipment are given and techniques are discussed to avoid the risk of inhalation of toxic concentrations of NO and NO2. This method provides the possibility of using inhaled NO with appropriate safety precautions in the range 0-60 ppm in a variety of continuous flow respiratory devices.

Polysulfone coating for hollow fiber artificial lungs operated at hypobaric and hyperbaric pressures.

Carbon dioxide transfer is increased when the gas phase of a hollow fiber membrane lung is operated at hypobaric pressures. Oxygen transfer is augmented by hyperbaric pressures. However, uncoated hollow fibers transmit gas bubbles into the blood when operated at a pressure greater than 800 mmHg and may have increased plasma leakage when operated at hypobaric pressures. Ultrathin polymer coatings may avoid this problem while reducing thrombogenicity. The authors coated microporous polypropylene hollow fibers with 380 microns outer diameter and 50 microns walls using 1, 2, 3, and 4% solutions of polysulfone in tetrahydrofuran by dipping or continuous pull through. These fibers were mounted in small membrane lung prototypes having surface areas of 70 and 187 cm2. In gas-to-gas testing, the longer the exposure time to the solution and the greater the polymer concentration, the less the permeation rate. The 3% solutions blocked bulk gas flow. The coating was 1 micron thick by mass balance calculations. During water-to-gas tests, hypobaric gas pressures of 40 mmHg absolute were tolerated, but CO2 transfer was reduced to 40% of the bare fibers. Hyperbaric gas pressures of 2,100 mmHg absolute tripled O2 transfer without bubble formation.

Small intrapulmonary artery lung prototypes. Mathematical modeling of gas transfer.

Two diffusion models have been developed to analyze gas transfer data previously measured in an intravascular artificial lung consisting of a central gas supply catheter from which are tethered a large number of blind-ended microporous fibers of equal length. A convective-diffusion model (CD) describes the countercurrent transfer of a binary gas pair when gas is supplied at constant pressure conditions, and a well mixed (WM) cycled pressure model predicts transfer when the gas supply pressure is time cycled between compression and vacuum conditions. Regression of gas to gas and liquid to gas excretion data with the CD model resulted in estimates of the liquid phase mass transfer coefficient kAI. Because these values were intermediate between the kAI expected for flow parallel to a cylinder and for flow normal to a cylinder, gas transfer was influenced by both the tethered region of the fiber that was nearly perpendicular to the axis of the test section and the free end of the fiber that rested along the wall of the test section. With a time cycled gas supply pressure, the enhanced carbon dioxide and oxygen excretion predicted by the WM model was similar to the data, but a loss in transfer efficiency with fiber length was not accounted for by the theory.

Small intrapulmonary artery lung prototypes: design, construction, and in vitro water testing.

Blind-ended, hollow fibers mounted on a pulmonary artery catheter may allow O2 and CO2 transfer in the vena cava, right ventricle, and pulmonary artery. The effects of fiber length, manifold number, and gas oscillation on mass and momentum transfer with water perfusate using mass spectrometry and mass flow controllers were studied. Manifolds with 112-196 microporous polypropylene fibers were mounted on 8 Fr multiple lumen, commercially available pulmonary artery catheters. Fiber lengths varied from 0.5 to 16 cm and surface areas from 7 to 220 cm2. Prototypes with 2 cm long fibers were constructed with 1-15 manifolds. A two manifold prototype with 8 cm long fibers and a surface area of 378 cm2 was also studied. The transfer failed to scale with manifold number because the steady gas flow was maldistributed to the manifolds. Oscillating gas pressures from 780 to 76 mmHg absolute at a rate of 40 cycles/min increased CO2 transfer up to 15-fold and O2 transfer up to 2.5-fold. Oscillation also corrected the maldistribution. Optimal fiber lengths of 3 and 1 cm for O2 and CO2, respectively, were seen with steady gas flow, and 8 cm for both with oscillatory gas flow.

Effects of blood phase oscillation on gas transfer in a microporous intravascular lung.

It may be possible to design an intravascular membrane lung with gas transfer properties augmented by the natural flow oscillations in the venous and pulmonary circulation caused by the beating heart and ventilatory movements. The authors used a simple dye visualization technique, the Pierce-Donachy assist pump, and mass spectrometry to investigate these effects on membrane lungs made with tethered, blind-ended, microporous, polypropylene fibers using in vitro tests in water saturated with O2, CO2, and He. Prototypes were constructed on a 7.5 Fr pulmonary artery catheter. The fibers had an outer diameter (OD) of 380 microns and a wall thickness of 50 microns and were mounted on 4.8 mm OD sleeves. Control measurements were taken over a range of steady water flows from 0.4 l/min to 3 l/min. While pumping the same water flow rates with a roller pump, the Pierce-Donachy pump generated pulsatile flow at a rate of 45 beats/min and a systolic duration of 300 msec. This produced a phasic flow with an instantaneous average flow velocity varying from 0 to as high as 46 cm/sec. O2 and CO2 transfer increased by as much as 91% and 59%, respectively. The largest effects were seen at the lower water flow rates.

Radiologic evaluation of the intravenous oxygenator.

This report describes the radiologic appearance of the intravenous oxygenator (IVOX), an intracorporeal CO2-O2 exchanger for use in patients with severe respiratory deficiency, and the extensive radiographic and sonographic support required for its use. Six patients aged 19-39 years who had severe adult respiratory distress syndrome (ARDS) and who were not expected to survive were selected for IVOX placement; ARDS was caused by trauma (four patients), severe pneumonia (one patient), or a fat embolus from a tibial fracture (one patient). Before insertion of the IVOX, all patients underwent evaluation of their right internal jugular vein, right common femoral vein, and inferior vena cava with real-time ultrasound (US) to ascertain vascular size. The IVOX improved oxygenation in all patients; because of such improvement, one patient survived. Use of the IVOX may become common; hence, radiologists should understand how the IVOX functions and its appropriate placement, be able to identify it on chest and abdominal radiographs, and appreciate the importance of US in placement of this device and follow-up.

Clinical trials of an intravenous oxygenator in patients with adult respiratory distress syndrome.

In patients with severe adult respiratory distress syndrome, mechanical ventilation may not be able to ensure gas exchange sufficient to sustain life. We report the use of an intravenous oxygenator (IVOX) in five patients who were suffering from severe adult respiratory distress syndrome as a result of aspiration, fat embolism, or pneumonia. IVOX was used in an attempt to provide supplemental transfer of CO2 and O2 and thereby reduce O2 toxicity and barotrauma. All patients were tracheally intubated, sedated, and chemically paralyzed and had a PaO2 < 60 mmHg when the lungs were ventilated with an FIO2 = 1.0 and a positive end expiratory pressure of > or = 5 cmH2O. The right common femoral vein was located surgically, and the patient was systemically anticoagulated with heparin. A hollow introducer tube was inserted into the right common femoral vein, and the furled IVOX was passed into the inferior vena cava and advanced until the tip was in the lower portion of the superior vena cava. IVOX use ranged from 2 h to 4 days. In this group of patients, IVOX gas exchange ranged from 21 to 87 ml x min-1 of CO2 and from 28 to 85 ml x min-1 of O2. One of the five patients survived and was discharged from the hospital. The IVOX transferred up to 28% of metabolic gas-exchange requirements. One patient with a small vena cava showed signs of caval obstruction. Three other patients demonstrated signs of a septic syndrome after the device was inserted.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of arterial gas embolism by increased end-tidal nitrogen in dogs.

Increased end-tidal (ET) nitrogen in a patient being ventilated with a nitrogen-free gas mixture through a leak-free circuit has been considered a specific sign of venous air embolism. We hypothesized that increased ETN2 would occur after arterial air emboli, just as following venous air emboli, and that clinically relevant arterial air emboli could be detected with respiratory gas monitoring by mass spectrometry. After approval from the institutional Animal Utilization Committee, eight mongrel dogs were studied. All were anesthetized with pentobarbital and ventilated with room air by a volume ventilator. Each animal was monitored by a femoral artery and a pulmonary artery catheter for systemic and pulmonary blood pressures, respectively, an electrocardiograph, pulse oximetry, and inspired and expired respiratory gas measurements by mass spectrometry. Arterial blood gas analysis was undertaken after one series of air emboli. Air boluses (containing the nonradioactive nitrogen isotope N2) of 50, 100, 200, and 500 mul/kg were injected slowly into the distal aorta through a second arterial catheter advanced 35 cm above the inguinal ligament. All emboli >/=100 mul/kg and 60% of the 50 mul/kg emboli were detected by increased ETN2 within 30 s, reaching peak levels in <2.75 min. The washout time for the N2 was longer for larger emboli, ranging from 2.9 +/- 2.8 min for 50 mul/kg emboli to 17.3 +/- 3.2 min for the 500 mug/kg emboli. There were no significant changes in end-tidal carbon dioxide, pulmonary or systemic blood pressures, or arterial blood gases. Increased ETN2 can no longer be considered pathognomonic for venous air embolism; arterial air embolism may have occurred.

Breath-by-breath monitoring of respiratory gas concentrations during compression and decompression.

We compared six systems for sampling respiratory gases from within a hyperbaric chamber to provide online gas concentrations by a mass spectrometer (MS) outside the chamber. Gas at hyperbaric pressure was sampled through either a capillary and mass flow controller (system 1), a capillary and micrometering manual valve (system 2), or a capillary alone (system 3) by a vacuum pump outside the chamber. In each system, a small amount of decompressed gas was drawn into the MS for analysis while the balance vented into the room. Systems 4-6 were constructed from systems 1-3, respectively, by eliminating the vacuum pump. Using a square wave respiratory simulator, which generated known gas concentration profiles within the chamber, MS analyses were recorded from each sampling system at compression and decompression rates of 20 meters of sea water.min(-1) and chamber pressures from 1.0 to 6.0 atm abs. Inspiratory and end-expiratory concentrations of nitrogen (0.0 and 1.0%, respectively) and carbon dioxide (0.0 and 4.2%, respectively) were accurately determined at respiratory rates of up to 70 breaths.min(-1) with a sensitivity of 0.05% and without pressure artifact.

Detection of venous air embolism by continuous mixed venous oximetry in dogs.

Continuous mixed venous oxygen saturation (SvO 2) was evaluated as a monitor of venous air embolism in a canine model. Nineteen dogs were anesthetized, paralyzed, and mechanically ventilated. Invasive monitoring included SvO 2, systemic and pulmonary artery blood pressures, and thermodilution cardiac outputs. Air boluses of 0.25 and 0.5 ml/kg were injected in six dogs and 1 ml/kg in all. All 1 ml/kg emboli were detected by greater than or equal to 5% decreases in the SvO 2. The SvO 2 decreased from 82 +/- 8% to 72 +/- 11% (mean +/- SD), an average decrease of 9 +/- 5% (p = 0.004). Time to the SvO 2 nadir was 2.6 +/- 2.5 min. Of the 0.5 and 0.25 ml/kg emboli, 50% and 17% were detected, respectively. Cardiac output decreased from 2.9 +/- 0.8 to 2.1 +/- 0.8 L/min after the 1 ml/kg emboli (p = 0.02). The 1 ml/kg emboli increased pulmonary artery pressures and decreased systemic blood pressure in 100% and 75% of animals, respectively. Peak changes in pulmonary artery pressure occurred at 1.2 +/- 0.8 min. In the present study, time to maximum change was greater for SvO 2 than for pulmonary artery pressure changes. Use of fiberoptic pulmonary artery catheters for continuous measurement of SvO 2 can add a new diagnostic modality to venous air embolism detection in patients who require a pulmonary artery catheter for other medical indications.

Venous air emboli with 15N2: pulmonary excretion and physiologic responses in dogs.

Venous air embolism occurs with decompression sickness as well as during a wide variety of surgical procedures in hospitalized patients. We developed a canine model to allow documentation and quantitation of pulmonary excretion of intravascular air emboli both in a control air breathing state and during treatment. We utilized 15N2 (a stable, nonradioactive isotope of room air nitrogen, 14N2) as the nitrogen component of venous air emboli (1 ml.kg-1) given to 27 anesthetized mongrel dogs ventilated with room air (tidal volume = 15 ml.kg-1). End-tidal 15N2 was measured and the embolism diagnosed by increased levels in exhaled gases. Exhaled gases were also collected in Douglas bags and the 15N2 recovered was quantitated by a helium dilution technique. Systemic and pulmonary artery pressure changes and quantitation of excreted 15N2 were documented after embolism during a control state with continued room air (21% oxygen) ventilation, and after treatments with either a) 100% oxygen ventilation; b) compression to 2128 mmHg, or 2.8 atm abs, and room air ventilation; or c) a combination of 100% oxygen ventilation and 2.8 atm abs compression. Increased end-tidal 15N2 was characteristic of all emboli, and use of 15N2 allowed accurate measurement of excreted gas during both room air and 100% oxygen ventilation. Embolic gas recoveries were not increased significantly by any of the treatments.

Hyperbaric nitrous oxide as a sole anesthetic agent in humans.

Nitrous oxide (N2O) has been used to produce analgesia and anesthesia for more than 100 yr. However, because of its high MAC value (1.04), general anesthesia with N2O can usually be attained only in a hyperbaric environment. Because of the sparsity of documentation for human physiologic responses to hyperbaric N2O, we studied eight male volunteers at 2 ATA (1520 mm Hg) anesthetized with N2O only for periods of 2-4 h. N2O partial pressures ranged from 836 to 1368 mm Hg. The anesthetic state was associated with tachypnea, tachycardia, increases in systemic blood pressure, mydriasis, diaphoresis, and at times, clonus and opisthotonus. A stable level of physiologic activity was difficult to maintain.

Detection of venous air embolism in dogs by emission spectrometry.

Emission spectrometers provide alternative, relatively inexpensive methods for detecting the concentration of respiratory gas nitrogen. Mass spectrometers are accepted as reliable monitors of end-tidal nitrogen for detection of venous air embolisms. We evaluated an inexpensive emission spectrometer for detecting changes in nitrogen levels and compared it with a mass spectrometer for detecting increased end-tidal nitrogen levels in dogs with venous air embolisms. During in vitro gas flow studies (helium; oxygen; helium/oxygen mixtures; or 70% nitrous oxide/30% oxygen with 0, 1, 2, or 3% isoflurane), air boluses (0.01 to 5.0 ml) were injected into a gas flow circuit and outlet nitrogen levels were measured by a Collins 21232 emission spectrometer. Responses were greater after each bolus when helium rather than oxygen was the major diluent gas. During in vivo studies, 5 dogs were anesthetized, ventilated, denitrogenated, and given venous air embolisms (0.1, 0.5, and 1.0 ml.kg-1) during oxygen and then during Heliox (20% oxygen:80% helium) breathing. End-tidal nitrogen increased approximately two-fold after venous air embolisms given during Heliox as compared with oxygen ventilation. In all 0.1-ml.kg-1 venous air embolisms end-tidal nitrogen increased when the emission spectrometer was used, but venous air embolisms less than 1.0 ml.kg-1 were not consistently detected by mass spectrometry. Emission spectrometry can be used to detect increased end-tidal nitrogen levels indicative of venous air embolism and may be a more sensitive detector than mass spectrometry.

Adult respiratory distress syndrome in the trauma patient.

A high mortality rate still exists for the patient with ARDS 20 years after the severe syndrome was first formally defined. Hypoxia and hypercarbia remain major clinical challenges requiring mechanical ventilation. The pulmonary vascular bed has been identified as a prime site of injury. The major working hypothesis is that cellular injury is caused by oxyradicals produced by activated neutrophils. There is no present pharmacologic therapy based on this hypothesis. Steroids have no demonstrable effect on outcome. Major advances have been made in the use of extracorporeal membrane lungs to relieve hypercarbia and hypoxia while minimizing pulmonary oxygen toxicity and barotrauma. The most promising current technique is extracorporeal CO2 removal during venovenous perfusion. Further advances must await definition of the early stages of the ARDS.

An evaluation of intra-cage ventilation in three animal caging systems.

Although temperature and relative humidity have been quantitated and their effects on research data studied, few studies have measured the air turnover rates at cage level. We evaluated the air distribution and air turnover rates in unoccupied shoe-box mouse cages, filter-top covered cages and shoe-box mouse cages housed in a flexible film isolator by using discontinuous gas chromatography/mass spectrometry and smoke. Results showed that air turnover was most rapid in the unoccupied shoe-box mouse cage and slowest in the filter-top covered cage. Placing mice in the filter-top covered cage did not significantly improve the air turnover rate. Although filter-top covered cages reduce cage-to-cage transmission of disease, the poor airflow observed within these cages could lead to a buildup of gaseous pollutants that may adversely affect the animal's health.

Carbon dioxide elimination during total cardiopulmonary bypass in infants and children.

The authors measured the rate of carbon dioxide elimination (VCO2) in 25 pediatric patients (age 2 days to 9 yr) during total cardiopulmonary bypass at average venous blood temperatures ranging from 19.5 to 35.9 degrees C. A multiplexed mass spectrometer was connected to the gas inlet and exhaust ports of the bubble oxygenator, and the gas-phase Fick principle was used to determine VCO2. A curvilinear relationship was found between log VCO2 and venous blood temperature, and a quadratic regression equation (r2 = 0.74) was fit to the data. Q10 (the ratio of VCO2 before and after a 10 degree C temperature change) was estimated to be 2.7 or 3.0, depending on the analytic method used. Venous blood temperature as a predictor variable explained a greater proportion of the variability of log VCO2 than did nasopharyngeal or rectal temperatures. Analysis of covariance revealed that total circulatory arrest during bypass (utilized in 10 patients for 34 +/- 4 min, mean +/- SEM) affected the relationship of venous blood temperature with log VCO2, by increasing the y-intercept (P = .008) but not the slope. These data, with associated 95% prediction intervals, define the expected CO2 elimination rates at various temperatures during standard bypass conditions in our patients. Real-time measurement of VCO2 using mass spectrometry can be a useful routine monitor during CPB that may help to assess patient metabolic function, adequacy of perfusion, and oxygenator performance.