Michael T. Snider

Pulmonary Hypertension in Severe Acute Respiratory Failure

We repeatedly assessed pulmonary and systemic hemodynamics in 30 patients undergoing therapy for severe acute respiratory failure of diverse causes. Pulmonary-artery hypertension and elevated pulmonar vascular resistance were observed in all patients after correction of systemic hypoxemia. Increasing pulmonary blood flow by isoproterenol infusion or decreasing pulmonary blood flow by partial bypass of the right side of the heart minimally altered pulmonary-artery pressure. Although neither elevated pulmonary vascular resistance nor low cardiac index reliably predicted death, survivors had preogressive decreases of pulmonary vascular resistance with time, whereas nonsurvivors tended to maintain or increase pulmonary vascular resistance. Right ventricular stroke-work index was markedly elevated in all patients. The work load imposed upon the right ventricle by elevation of pulmonary vascular resistance may be a factor limiting survival in severe acute respiratory failure.

Increased N-pentane Excretion in Humans: A Consequence of Pulmonary Oxygen Exposure

Lipid peroxidation by free radicals has been suggested as a mechanism of a lung injury caused by breathing higher than normal concentrations of oxygen. The appearance of hydrocarbons such as n-pentane in the expired gas of mammals has been proposed as in vivo evidence of lipid peroxidation. The excretion of n-pentane was studied in 15 healthy volunteers in whom excretion of exogenous n-pentane was determined over a 60- to 90-min period while breathing hydrocarbon-free gases. N-pentane elimination rates (mean ± SEM) in the expired gas at 0, 30, 60, 90, and 120 min were 10.2 ± 1.5, 1.6 ± 0.2, 1.2 ± 0.9, 1.3 ± 0.4, and 1.3 ± 0.3 (pmol · kg−1 · min−1), respectively. Using a specially assembled circuit, a 2-h oxygen exposure study was performed on six healthy volunteers, in whom basal n-pentane excretion varied ten-fold among individuals, from 0.25 to 2.25 pmol · kg−1 · min−1. After breathing 100% oxygen, npentane excretion was augmented 62–420% within 30 to 120 min. The authors conclude that lipid peroxidation may occur in humans within 30 min of breathing 100% oxygen.

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)

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.

Pathophysiologic Pathways of the Adult Respiratory Distress Syndrome

To achieve a better understanding of the pathogenesis of acute lung injury and effective prevention and therapy, the intensive care physician must recognize that most hospitalized patients with acute lung disease fall into two broad categories: 1) A large group has ‘classic’ pulmonary complications. These often develop after surgery and are due to small airway closure, atelectasis, and/or pulmonary edema resulting from an elevated left atrial pressure without abnormally increased microcirculatory permeability. This type of acute respiratory failure (ARF) is characterized by preservation of basic pulmonary architecture, and as a rule it is preventable and reversible provided effective treatment is instituted early [43]. 2) A smaller population in which diffuse alveolar capillary membrane injury is commonly diagnosed as the adult respiratory distress syndrome (ARDS) [23, 40, 41]. Table 18.1 lists some of the diverse conditions which can produce this type of severe lung injury; each injury is characterized by an increased permeability to plasma proteins by the alveolar capillary membrane. Table 18.2 suggests possible pathophysiologic mechanisms leading to the acute lung injury.

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.

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°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°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.

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.

Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Failure. A Randomized Prospective Study

Nine medical centers collaborated in a prospective randomized study to evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a therapy for severe acute respiratory failure (ARF). Ninety adult patients were selected by common criteria of arterial hypoxemia and treated with either conventional mechanical ventilation (48 patients) or mechanical ventilation supplemented with partial venoarterial bypass (42 patients). Four patients in each group survived. The majority of patients suffered acute bacterial or viral pneumonia (57%). All nine patients with pulmonary embolism and six patients with posttraumatic acute respiratory failure died. The majority of patients died of progressive reduction of transpulmonary gas exchange and decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis. We conclude that ECMO can support respiratory gas exchange but did not increase the probability of long-term survival in patients with severe ARF.

Week long partial pulmonary bypass with an artificial lung pumped by the right ventricle.

Extracorporeal pumping PA-LA perfusions were carried out for 24 hrs in 5 awake, alert lambs by cannulating the main PA and the LA with large bore polyurethane cannulae. A mean of 42% of the basal cardiac was pumped through the membrane lung. When the PA occluder cuff was progressively inflated, up to 80% of the basal cardiac output was diverted to the extracorporeal circuit for short periods. Hemothorax remained a significant problem. Three lambs were electively perfused 12 hrs, 36 hrs, and 8 days without a roller pump, using a low resistance spiral coil membrane lung pumped by the RV. By inflating the occluder cuff, a mean of 55% of basal cardiac output was pumped by the RV through the membrane lung. The 8 day bypass lamb remained healthy and active without any bleeding or gross pathology. We did not observe air emboli, thromboemboli or gross infections in either group. We believe that such a mode of cannulation will eventually allow long-term perfusion of a low resistance membrane oxygenator driven directly by the RV.