Cannulation of the proximal aorta during long-term membrane lung perfusion.

Prolonged extracorporeal oxygenator support for acute respiratory failure is a clinical reality. Recent experience with 4 patients has demonstrated an advantage in delivery of saturated blood to the root of the aorta during venoarterial (VA) bypass. We have been able to perfuse the heart and bilateral cerebral hemispheres by advancing the tip of a large perfusion cannula to the aortic root from the common femoral artery. When the catheter did not pass beyond the transverse aortic arch, there was marked asymmetry of oxygenator perfusion, as determined by differential oxygen tension in right and left radial artery blood and by xenon-133 scans following isotope injection into the arterial return line. Long-term VA bypass lasting from 5 to 11 days resulted in long-term survival in 2 patients with post-traumatic gram-negative pneumonitis. The other patients, who had viral pneumonitis and post-transfusion respiratory failure, died after 9 and 11 days of membrane oxygenator support. No embolic lesions or arterial or valvular injuries were discovered at autopsy. This is a safe and useful method of providing oxygenated blood to the aortic root for equal distribution to the rest of the body.

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.

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.

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.

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.

High-frequency ventilation at rates of 375 to 1800 cycles per minute in four neonates with congenital diaphragmatic hernia.

Neonates with congenital diaphragmatic hernias (CDH) often die because of pulmonary hypoplasia and high pulmonary vascular resistance (PVR). Pulmonary hypertension and right-to-left shunting precedes progressive hypoxia and death. PVR is increased by acidosis and by high airway pressures. High-frequency oscillation (HFO) is a new technique which may improve the outcome for such infants. Gas exchange in HFO is achieved by directing rapid pulsations of small volumes of gas down the trachea, typically at rates greater than 200 cycles per minute, volumes less than 25% of dead space, and low airway pressures. Gas transport results from augmented diffusion, not from bulk flow. Four neonates with CDH deteriorated on conventional mechanical ventilation and required hand ventilation at rates above 200 per minute. HFO at frequencies from 375 to 1800 cycles per minute was then initiated using a flow-interrupter type of oscillator. A marked fall in PaCO2 and a rise in pH resulted. The elimination of CO2 was very efficient with low mean airway pressures (less than 15 mm Hg). The initial improvement during HFO probably resulted from a decrease in PVR due to reversal of the acidosis. However, all four babies died after 13 to 80 hours of HFO. Neonates with CDH who remain hypercapneic despite conventional mechanical ventilation can be successfully ventilated by HFO. Use of HFO produces respiratory alkalosis which may stabilize PVR in the normal range and improve survival rate.

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.

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: 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.

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.

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.

A comparison of continuous and discrete foreign gas VA/Q distributions.

Estimates of ventilation-perfusion ratio (VA/Q) distributions from foreign gas infusions have utilized a discrete lung model that constrains all alveoli to have 1 of 50 specified VA/Q. In contrast, distribution estimates based on a continuous model allow alveoli to have any VA/Q and can be derived directly from foreign gas data or by transforming distributions derived using the discrete model. We have compared analytically and empirically the properties of distributions based on these two models. Unlike the discrete model, the shape of distributions obtained from the continuous model are insensitive to changes in the VA/Q used in their calculation. Perfusion distributions found from the discrete model using VA/Q values evenly spaced on a logarithmic scale resemble ventilation distributions derived from the continuous model. In contrast, by use of VA/Q evenly spaced on a linear scale, perfusion distributions derived from either model have a similar shape. We concluded that physiological inferences derived from distribution shapes may vary according to the model employed. However, those based upon cumulative perfusion or distribution moments are invariant.

Accumulation of methane, acetone, and nitrogen in the inspired gas during closed-circuit anesthesia.

During closed-circuit anesthesia, the patient's inspired gas may become progressively contaminated by nonanesthetic gases. We studied the concentrations of methane, acetone, and nitrogen as nonanesthetic gas contaminants in the circuit gas of 16 cases during closed-circuit anesthesia. After a "short" period of denitrogenation (6-8 min), average nitrogen concentration in the closed circuit increased from 6.4 to 16.2%, methane from 4.3 to 22.4 ppm, and acetone from 0.3 to 2.2 ppm. After "long" denitrogenation (33 min), average nitrogen concentration in the closed circuit increased from 1.0 to 5.1%, methane from 3.7 to 17.9 ppm, and acetone from 1.3 to 5.9 ppm. It is concluded that gases stored in tissues or produced within the body can appear in the patient's expired gas during closed-circuit anesthesia. Intermittent flushing of the circuit with high flow gases is suggested to remove these contaminants.

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.

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 X kg-1 X 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 X kg-1 X min-1. After breathing 100% oxygen, n-pentane 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.

Reaction to ketamine: anaphylactoid or anaphylactic?

A 3-year-old child developed extensive macular rash after ketamine. The mechanism of this reaction was investigated by the Prausnitz-Kutzner (P-K) test. It demonstrated that the histamine release was not the result of an anaphylactic reaction, but rather a direct pharmacological effect of the drug. The result suggests that this child can receive ketamine in the future without any severe manifestations. The mechanisms of histamine release are discussed and the treatment of its clinical manifestations is reviewed.

Rapid induction of halothane anaesthesia in man.

The cardiopulmonary and anaesthetic responses of nine healthy volunteers, breathing concentrations of 1-4% halothane in oxygen, were studied. Supine fasting subjects breathing room air exhaled to residual volume and then inhaled a vital capacity breath of 1, 2, 3 or 4% halothane in oxygen. After a breath-hold of 30-90 s they exhaled and then breathed spontaneously the same anaesthetic mixture for up to 2 min. The electrocardiogram, arterial pressure, heart sounds and arterial oxygen saturation, were monitored, and respiratory gases were analysed by mass spectrometry. The maximum effect was seen after breathing 4% halothane. All volunteers were amnesic after the first breath and unresponsive to command after 2 min. Little or no excitement occurred. A maximum decrease of 12 mm Hg in systolic pressure was seen while breathing 4% halothane. Bradycardia, hypoxia and clinically important hypercarbia did not occur. At all inspired concentrations of halothane, the end-tidal halothane concentration increased rapidly and was 30% of the inspired value after 1 min. No volunteer found this technique to be unpleasant. Rapid induction of general anaesthesia with 2-4% halothane in oxygen is effective, safe and well accepted by healthy young adults.

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.

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.