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Recent Advances in Pediatric Inhalation Therapy
Recent Advances in Pediatric Inhalation Therapy DAVID ALLAN, M.B., OR.B.*
Inhalation therapy is achieved by the quantitative modification of the respired atmosphere, the aim being adequate cellular oxygenation and carbon dioxide elimination. The atmosphere is modified mainly by altering the percentage of oxygen content, altering the water content, introducing therapeutic agents, and increasing the pressure of the atmosphere. Inhalation therapy is an old science, the first Institute of Pneumotaxics having been formed in Bristol, England, in the nineteenth century, but it is only within recent years that there has been a renewal of interest in this therapy. In the practice of pediatric inhalation therapy, there have been some spectacular advances particularly in the methodology of nebulization, sterilization of equipment, intermittent positive pressure respiration eLP.p.R.) and hyperbaric oxygenation.
NEBULIZATION
The rationale upon which the use of nebulizers is based involves a basic knowledge of the physics of fluids and gases and the physiology and pathology of the humidification apparatus of the respiratory system. The actual mass of water contained in a certain volume of air is known as the absolute humidity of that air. There is a definite limit to the amount of moisture which a volume of air can hold at any given temperature; this is known as the maximum humidity. Humidity deficit is the difference between maximum and absolute humidity at any given temperature. The amount of moisture which the air can contain varies directly with the temperature, that is, it increases with a rise in temperature and decreases with a fall in temperature. Relative humidity is defined as the ratio between • Assistant Professor of Surgery, Northwestern University Medical School; Director of Anesthesiology and Inhalation Therapy, The Children's Memorial Hospital, Chicago, Illinois
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DAVID ALLAN
the mass of vapor actually present in the atmosphere and the maximum which the atmosphere is capable of holding at a given temperature. Density and buoyancy are important factors which affect the suspension of particles. Density is defined as the ratio of the mass of a body divided by its volume. The lower the temperature of a gas at a constant pressure, the greater its density. Archimedes' principle states that all bodies completely or partially immersed in a fluid are buoyed up by a force equal to the weight of the fluid displaced. Therefore, if the weight of a body is less than the weight of the fluid it displaces, the body will float in the fluid. In considering these factors it is important to realize that gases and fluids are governed by the same laws. Viscosity, defined as the internal friction of resistance to deformation of a fluid, plays the paramount role in determining the laminar flow rate of a substance through a tube. In turbulent flows, the density of the fluid, rather than theyiscosity, plays the important part in determining its volume flowrate. Room air normally has a humidity deficit~ When the air is inspired, the air is warmed from approximately 21 0 C. to 370 C. in the proximal airways. This further increases the humidity deficit, for even if the air were fully saturated at 21 0 C., heating to body temperature would produce a humidity deficit. The muco,us membranes of the nose and to a lesser degree the oropharynx and tracheobronchial tree contain the humidifying mechanism. In an adult, 1 liter of water is used in 24 hours to supply this humidifying mechanism, and there is a relatively higher requirement per square meter of body surface in the child with its higher metabolic rate (Fig. 1). Disease producing pyrexia and increased minute volume further increase the demand. Thus, the cardinal rule is adequate hydration of the patient as a whole. Dehydration will impair tl;tenormal ciliary activity2, 7, 8 and mucus will be retained. The greater the retention of secretions, the greater the culture medium available to propagate harmful bacter~. Any impairment of the humidification mechanism (for example, by an upper respiratory infection or by being bypassed by an endotracheal tube or tracheostomy) will produce retention of secretioIls which are mechanically obstruc" tive and are potential media for bacteria growth. The best method of treatment of an absolute humidity deficit is nebulization. The mechanical nebulizer is the type presently being used and the size of particles produced is determined by its structural design and inlet pressure. Basically, the Ilebulizer cQnsists of a capillary tube partially submerged in the fluid~o be nebulized, and a jet orifice that blasts a gas stream across the tip'of the capillary tube, thereby creating a negative pressure at this point (the Bernoulli principle) and sucking the fluid up the capillary tube. Thejetstrell
RECENT
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IN PEDIATRIC INHALATION THERAPY
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Numerous studies of the physical factors which determine the site and quantity of deposition of water particles in the tracheobronchial tree have been published. 6, 9, 20, 21 Particle size largely determines the site of depositionjlo that for the lower bronchi and alveoli is 1 to 3 IL, for intermediate bronchi 3 to 5 IL, and for the trachea and larynx 5 to 8 IL. 20 , 25 Particle sizing is accomplished either by the absolute method3 , 10, 12, 23, 26 or by the Casella Cascade Impactor Method. 4 , 13, f9, 27 Both methods are technically difficult and for this reason many nebu,lizers are released for use on patients without performance data being available Some believe that to deliver particle sizes in the 1 to 3 IL range, it is necessary to include in the stream a percentage of the larger particles, 6 .to 8 IL, which prevent the smaller sizes from "raining out" in the upper respiratory tract, but others believe that the particles should be of a uniform size. The volume of water nebulized per unit time and per unit air flow is important but no scientifically determined specifications existed until the advent of the Herzog nomogram (Fig. 1). H eaJ,ed nebulizers are still being investigated. The principle of the heated nebulizer is that by raising the temperature of the humidity delivered at the patient to body temperature, there will not be a humidity deficit. Thus the temperature at the nebulizer itself must be above body temperature (120° F. in the Puritan) and should be varied in direct proportion to the length of the connecting tubing. The opponents of this technique argue that the air stream is so lightened that there is not sufficient buoyancy to carry the particles far enough down the respiratory tract. In our preliminary investigation we have found the heated nebulizer to be efficacious in the management of the infant with a tracheostomy. This year saw the introduction of the ultrasonic aerosol generator (Fig. 2). The particle size is a direct function of the ultrasonic frequency generatedP It is thus possible to predict and influence the body water balance through the airways. These nebulizers have an efficiency fifteen times greater than the best mechanical ones. They will have an unlimited use in intermittent positive pressure breathing, tracheostomy humidification, and non-rebreathing anesthesia circuits; but in pediatric inhalation therapy, it should be remembered that these nebulizers are very efficient and this efficiency can cause overloading of the circulation if the vaporizer is not regulated with care. One of these generators can nebulize 0.72 grams of physiological saline per minute in a closed circuit. 14 An experimental model designed for open circuit use is said to generate ten times this amount. The ultrasonic aerosol generator is probably the biggest advance in inhalation therapy in a century.
The Pediatric Air Oxygen Aerosol Mist Tent At Children's Memorial Hospital we have developed a pediatric air
DAVID
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ALLAN
12 DROPS,/Iml'n
11 10
9
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8
7 6
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\1\ I\~ f\.~1'-..1":1'-.. I""'I\~ 1"1'- 1"-1' ~ ~b - - ---[\ t'" 1'.... k'I'1"- l' t-r-j:::: l' t-j::: t-- !:::f::+:::r",1"- t-..,.J'-.. I--=E t:-' ~ 1r-;...: 'I'-1=:: t-I=: I-;-t- r-t= I-t- t-
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\:::
9i11 U ~ U ~.n n VTot I/min
Figure 1. Nomogram for the prediction of the amount of humidity of inspired gas and the net gain of water of the patient at different drop rates to the ultrasonic nebulizer. The intersection between a line drawn from VTot and the drop-rate curve indicates the concentration of humidity as read off on the left-hand ordinate (H20, g!m3VTot). The value read off at the "net gain" ordinate multiplied with the value for alveolar ventilation (VA) in cubic millimeters gives the net gain of water of the patient. VAhas to be calculated as VA = VTot - (VDResP. + VDpat)· The "net gain "ofthenomogram includes the humidity of the standard humidifier of the Engstrom respirator, which gives a humidity of 12 gm. of water per cu. mm. of inspired gas. Room-air humidity is not included. (Herzog, P. et aI., Acta anaesth. scandinav. 8: 79,1964.)
RECENT ADVANCES IN PEDIATRIC INHALATION THERAPY
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oxygen aerosol mist tent using an efficient mechanical nebulizer. The requirements that we established were: 1. It should be possible to vary the volume of the tent according to the size of the child, and to raise the side rails of the cribs to their fullest extent. 2. The temperature of the environment of the child should be controllable. 3. Humidification in the tent should be 100 per cent in the micron size 1 to 8 J.I. with no particles over 10 J.I. which would "rain out" and wet the patient. 4. The nebulizer should be driven by oxygen or compressed air. 5. The elimination of CO 2 should be efficient. 6. Everything in contact with the patient should either be disposable or autoclavable. From Figure 3 it can be seen that the tent is adjustable in height and actually is suitable for adult use. Figure 4 demonstrates that the side rails can be fully elevated, and that the temperature of the environment
Figure 2. The Herzog ultrasonic aerosol generator being used in an anesthetic non-rebreathing circuit.
DAVID ALLAN
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Fig. 3
Figure 3. The Allan-Walsh pediatric air oxygen aerosol tent showing its versatility in size. Figure 4. The pediatric tent with the side rails fully elevated. The temperature is monitored with a thermometer. Note the dense mist which does not cause a "rainout."
Figure 5. Although the Allan-Walsh pediatric air oxygen aerosol tent is not arecirculating tent, a high flow of 13 liters eliminates C02 accumulation .
RECENT ADVANCES IN PEDIATRIC INHALATION THERAPY
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Figure 6. The Allan-Walsh pediatric air oxygen aerosol unit packaged for autoclaving and subsequent storage.
is monitored and controlled. There is no "rain-out," yet the mist is so dense that it is difficult to see the patient. IS The nebulizer can be driven by either compressed air or oxygen. This is an excellent combination for the treatment of cystic fibrosis. The unit is a noncirculating one with a high flow of 13 liters which precludes CO 2 accumulation (Fig. 5). The performance was checked, in the finished product, by actual measurement and found to conform to all the specifications. The canopies are disposable and everything in contact with the patient is autoclavable (Fig. 6). STERILIZATION OF EQUIPMENT
Cross infection with inhalation therapy equipment acting as the carrier has always concerned us. These new air oxygen mist units* have
* Aquastream Mist-O.-Gen Air Oxygen Tents, Mark II, Children's Memorial Hospital (1) Allan-Walsh Model. Supplied by Liquid Carbonic Division of General Dynamics. Canopies, Allan-Walsh design.
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DAVID ALLAN
done much to eliminate the potential hazard. They can do the work previously done by oxygen tents, air tents, croupettes, croup tents and Walton humidifiers, and do it much more efficiently. Simplicity of design generally reduces maintenance, and this has proved true in actual use despite the fact that the component parts are autoclavable. Gas sterilization of inhalation therapy equipment leaves much to be desired, for the results are not absolute and the technique is slow and expensive. The slowness necessitates additional equipment. Ideally, all inhalation therapy equipment should be either disposable or autoclavable. This will be difficult to achieve in pediatric inhalation therapy as two of the most important pieces of equipment are incubators and ventilators which are complicated mechanisms constructed, in essential parts, of non-autoclavable materials.
THE INCUBATOR Incubators have proved to be most difficult to sterilize. They evolved from the Hess bed which was fitted with a humidification system. The requirements for environmental control of the infant have been poorly understood. We are still at the "hot box" stage. With great difficulty we have managed to eliminate pathogenic organisms in incubators using culture control to check the efficacy of sterilization techniques. New humidification systems were installed in the older model incubator. All reservoirs are siphoned off after use. New type gaskets were installed making cleaning very much easier. Amphyl* is the sterilizing solution. It is interesting to note that we have multiple oxygen limiters on some of our incubators. It is our belief that the critical factor in the production of retrolental fibroplasia in the premature infant is the p02 of the arterial blood, which should be monitored and limited to normal (100 mm. Hg). The oxygen in the atmosphere should be limited to a range of 30 to 100 per cent depending on the arterial p02 of the infant. The most obvious illustration of this concept is a premature infant with a central arteriovenous shunt. An infant with an oxygen saturation of 25 per cent most certainly will not suffer any sequelae from the use of 100 per cent oxygen in the atmosphere. The main feature of an intensive care incubator should be immediate accessibility of the patient. Both companiest supplying this type of incubator have complied with our wishes. Our intensive care units have become quite elaborate with servo temperature controls and manifolds for electrocardiographic leads, pressure manometric catheters and ventilator hoses.
* Amphyl supplied by Lehn & Fink Products Corporation.
t Supplied by Air Shields and Ohio Chemical.
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INTERMITTENT POSITIVE PRESSURE RESPIRATION (IPPR) IN INFANTS
It has only been in the last three years that it has been possible automatically to ventilate infants satisfactorily. The requirements for an infant ventilator are quite challenging.22 It must be capable of generating variable flows, down to very slow rates, allowing laminar flow, more equal distribution of gases and a lower cycling pressure. The dead space must be extremely low and the resistance to expiratory flow must be controllable and variable to deal with low compliance. The apparatus and connections should be lightweight and sterilizable or disposable. Unfortunately, none is autoclavable. There are two basic types of ventilators available, the volume limited Engstrom and the volume variable Bird Mark 8 and Bennett PR2 with Q circle. In our opinion, normal respiration in the infant is volume variable so that the Bird Mark 8 with Q circle was chosen for the ventilation of our infants. It has proved to be satisfactory but far from perfect, as it, like all ventilators, is of basic adult design. There is a big difference in shifting a volume of 15 cc. and a volume of 500 cc. The Bennett PR2 with Q circle is acceptable if fitted with an expiratory retard mechanism. The timing of its nebulizer is slightly superior to that of the Bird Mark 8 as it preloads the circuit with humidifying particles before inspiration begins. All entrainment mechanisms are notoriously inaccurate. Should there be concern about the possible production of retrolental fibroplasia, the ventilator should be driven by compressed air. The exponents of the volume limited technique insist that it is absolutely necessary to have a constant deliverance of oxygen to the alveoli. The main points of management of intermittent positive pressure breathing have been frequently described.H We have had considerable experience in the management of infants1 and there are several points that require special emphasis and care. By far the most important is the collection and training of a large and dedicated staff as the patients are very ill and are often in precarious condition. They demand a constant watch and frequent attention: any alteration in any parameter must be noted immediately, properly assessed, and any necessary action performed promptly. A team of anesthesiologist, inhalation therapist, cardiologist, surgeon, bronchologist and intensive care nurse must be available 24 hours a day and seven days a week. The improvement in our team has been reflected in the gradual improvement of our salvage rate (in all cases of IPPR including postoperative infants). In approximately one-quarter of our patients, the maintenance of life has been shown to be impossible because of inadequate surgical correction of the defects involved. Along with. an intensively trained team, an intensive monitoring program is necessary. The patient is nursed on an automatically temperature controlled water-alcohol blanket or in a temperature servo controlled
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incubator and kept at any preset desired temperature, recorded and controlled by a thermistor. The electrocardiograph is continually demonstrated by oscilloscope with an alarm system to warn immediately of the occurrence of bradycardia. The respirator settings initially required are noted and alterations made as compliance varies, as indicated by a change in respiratory time. Normal spirometers such as the Wright are unsuitable for infants as the air flow is too small to drive the vanes. Weare introducing to our armamentarium a servo spirometer with an accuracy to 2 cc. to overcome this problem. The alveolar CO 2 can be monitored as an additional aid, using a Beckman 190 gas analyzer. The most important parameters to be monitored are the arterial pH, pC02, p02 and oxygen saturation. There is a risk of complications in leaving an arterial catheter in an infant, but it is one that should be accepted. A capillary technique is unsuitable as the infants are usually in peripheral vasoconstriction. Standard bicarbonate and plasma electrolytes are measured daily. We are attempting to introduce a thermistor cardiac output technique which should be a great aid in the management of the infant during IPPR. Initially, respiration is controlled, but patient cycling is allowed when a suitable rate is established. Tachypnea is almost constant initially and tends to recur whenever ventilation is reduced for any reason, so that control frequently has to be re-established. The initial settings produce hyperventilation as patients have respiratory acidosis. Control is usually achieved at arterial pC0 2 leveis of 20 to 30 mm. Hg, pH 7.4 to 7.5. Subsequent adjustments to respiratory rates and volumes in an attempt to maintain these levels are made on clinical judgment, published nomograms giving only a very rough indication of requirements in this size of patient. Values in many patients with partially corrected cyanotic heart disease are variable, however, and can only be used to judge the progress of that particular case. The use of tromethamine (THAM) has greatly aided in the management of the cyanotic infant, but complicates the respiratory biochemical control. The major problem in the management of infants undergoing IPPR is the maintenance of an adequate airway. Tracheostomy in an infant carries with it a considerable death rate (30.7 per cent).15 The main causes for this, other than basic underlying pathology, are inadequate humidification following the bypassing of the normal humidifying mechanism and poor suction technique. Results following the use of the ultrasonic aerosol generator in such patients are being awaited with great interest. An absolutely sterile technique of suctioning is essential-sterile gloves, catheters, and washing water for each suction; therefore, at least two nurses must be present. Speed is also important, so that one nurse disconnects the ventilator while the other puts the suction catheter into the trachea, allowing suction only on withdrawal, giving only one suction at a time, and allowing a few minutes of IPPR in between. The automatic monitor with
RECENT ADVANCES IN PEDIATRIC INHALATION THERAPY
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an alarm system (Electrodyne) has been found to be life-saving in giving warning of bradycardia during suctioning. Segal has developed an ingenious method for overcoming bradycardia during suctioning. 24 This method allows for suctioning during the inspiratory cycle of the ventilator. Endobronchial suction is given as one or the other lung shows signs of obstruction. It may be accomplished under direct vision or an angulated suction catheter may be used." In patients who are fit enough, suction is preceded by use of a bronchodilator, percussion and postural drainage. Frequency of suction is reduced as soon as possible to hourly or two hourly intervals to minimize the possibility of tracheal trauma and introduction of infection. Bronchoscopic suction is required for the removal of large and viscous plugs-often repeatedly in the same patient. Antibiotic cover is essential, but, despite this, gross infection is not infrequently the major cause of death. The new Great Ormond Street tracheostomy tube* designed by Ian Aberdeen is an excellent tube for use with a ventilator. It has a single lumen with its orifice funnel shaped to accept the ventilator connection. The correct selection of a size for the trachea dispenses with cuffs which can slip off. There may be some leak, which can be compensated for by the ventilator. Every effort is made to end IPPR as early as possible, allowing periods of spontaneous respiration of increasing length according to the infant's capacity. IPPR of an infant is difficult, management of the airway most challenging, but success most rewarding. PHARMACOLOGY
Progress in the pharmacology of inhalation therapy has on the whole been rather disappointing. Infants cannot manage sodium chloride as well as children or adults so that sterile water, in spite of its irritant properties, should be used in preference to saline for humidification. Isoproterenol is still the best bronchodilator. It must be ruefully admitted that water, saline and isoproterenol are the only proven efficacious aerosol pharmacologic agents in inhalation therapy. Our knowledge of the effects of oxygen has increased from the stimulus of the use of hyperbaric oxygenation. HYPERBARIC OXYGENATION
Professor Illingworth of Glasgow very aptly and succinctly described the present status of hyperbaric oxygenation, in words to the effect that much research was still to be done in basic physiology, pharmacology and
* S. Smith & Sons (Canada)
Ltd., distributors.
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DAVID ALLAN
pathology before the overall place of hyperbaric oxygenation in our therapeutic armamentarium could be assessed. Oxygen under from one to four atmospheres has been investigated as a therapeutic agent in Scotland, H011and and America. Hyperbaric oxygenation at one to two atmospheres is the treatment of choice of carbon monoxide poisoning. The patients are placed in mobile chambers, and in 20 minutes the vast majority are awake and well. Other conditions such as tetanus infections produced by anaerobic organisms, infections produced by aerobic organisms, and cyanotic heart disease are in the process of being investigated.
SUMMARY
Pediatric inhalation therapy has taken a great surge forward in recent years. The outstanding achievements are in nebulization, sterilization, intermittent positive pressure breathing especially in the infant, and hyperbaric oxygenation. A great deal of research is being conducted in this field and much is expected of this form of therapy in the future.
REFERENCES 1. Allan, D. and Kay, B.: Management of infants with postoperative respiratory distress. Submitted for publication. 2. Bellenger, J. J.: A study of ciliary activity in the respiratory tract of animals. Ann. Otol. Rhin., & Laryng. 68: 351, 1949. 3. Bennett, A. H., Osterbert, H., Jupnik, H. and Richards, O. W.: Phase Microscopy, Principles and Applications. New York, John Wiley & Sons, 1951. . 4. British Standard 28, 1957. 5. Bush, G. H.: Tracheobronchial suction in infants and children. Brit. J. Anaesth. 36: 322, 1963. 6. Cushing, J. E. and Miller, W. F.: Considerations in humidification by nebulization. Dis. Chest 34: 388, 1958. 7. Dalham, T.: Mucus flow and ciliary activity in the trachea of healthy rats and rats exposed to respiratory irritant gases. Acta physiol. s(',sndinav. S3: Suppl. 123, 1956. 8. Dalham, T.: Studies of the effect of sulphur dioxide on ciliary activity in rabbit trachea in vivo and in vitro and on the resortional capacity of the nasal cavity. Am. Rev. Resp. Dis. 83: 566, 1961. 9. Dantrebande, L.: Studies on aerosols. University of Rochester Atomic Energy Project, UR 530, October, 1958. 10. Fuchs, N. and Petryanoff, J.: Nature 138: 111, 1937. 11. Gilston, A.: Management of respiratory distress after cardiothoracic surgery. Thorax 17: 139, 1962. 12. Green, H. L.: Some accurate methods of determining numbers and size-frequency of particles in dust. J. Indust. Hyg. 16: 29,1934. 13. Green, H. L. and Watson, H. H.: Unpublished Report, Particle Clouds, p. 304 E & FN, Sponlid, London, 1957. 14. Herzog, P., Norlander, O. P. and Engstrom, C. G.: illtrasonic generation of aerosol for the humidification of inspired gases during volume controlled ventilation. Acta anaesth. scandinav. 8: 79, 1964.
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15. Holinger, P., Brown, W. and Maurizi, D.: Tracheostomy in the newborn. Accepted for publication, Pediatrics. 16. Lovejoy, F. W., Constantine, H. and Dantrebande, L.: Importance of particle size in aerosol therapy. Proc. Soc. Exper. BioI. & Med. 103: 836, 1960. 17. Matausechck, J.: Einfuhrung in die Ultraschalltechnik. August, 1961, VED, Urlag Tech., Berlin. 18. Matthews, L. W., Doershuk, C. F., Wise, M., Eddy, G., Nudleman, H. and Spector, S.: A Therapeutic Regimen for Patients with Cystic Fibrosis. Department of Pediatrics, Western Reserve University School of Medicine, Cleveland, Ohio. 19. May, K. R.: J. Scientific Instr. es: 187, 1945. 20. Mitchell, R. I. : Retention of aerosol particles in the respiratory tract. A review. Am. Rev. Resp. Dis. 8S: 627, 1960. 21. Morrow, P. E.: Physical and physiological factors controlling fate of inhaled substances. Proc. 4th Ann. Meet. on Bio-Assay and Analytical Chemistry. AEC Research and Development Report, Washington 1023, Nov., 1958. 22. Mushin, W. W. and Mapleson, W. W.: Problems of automatic ventilation in infants and children. Brit J. Anaesth. 34: 516, 1962. 23. Salem, H. and Cullumbine, H.: Toxicology and Applied Pharmacology, Vol. 2. 1950, pp. 183-187. 24. Segal, S.: Personnal communication. 25. Shwachman, H.: Therapy of cystic diseases of the pancreas. Pediatrics e5: 1551, 1960. 26. U.S. Public Health Service, Public Health Monograph 959, No. 60. 27. University of Michigan, Encyclopedia of Instrumentation for Industrial Hygiene. Ann Arbor, Michigan, 1956, pp. 142 and 178. 707 Fullerton Avenue Chicago, Illinois 60614
Inhalation therapy is achieved by the quantitative modification of the respired atmosphere, the aim being adequate cellular oxygenation and carbon dioxide elimination. The atmosphere is modified mainly by altering the percentage of oxygen content, altering the water content, introducing therapeutic agents, and increasing the pressure of the atmosphere. Inhalation therapy is an old science, the first Institute of Pneumotaxics having been formed in Bristol, England, in the nineteenth century, but it is only within recent years that there has been a renewal of interest in this therapy. In the practice of pediatric inhalation therapy, there have been some spectacular advances particularly in the methodology of nebulization, sterilization of equipment, intermittent positive pressure respiration eLP.p.R.) and hyperbaric oxygenation.
NEBULIZATION
The rationale upon which the use of nebulizers is based involves a basic knowledge of the physics of fluids and gases and the physiology and pathology of the humidification apparatus of the respiratory system. The actual mass of water contained in a certain volume of air is known as the absolute humidity of that air. There is a definite limit to the amount of moisture which a volume of air can hold at any given temperature; this is known as the maximum humidity. Humidity deficit is the difference between maximum and absolute humidity at any given temperature. The amount of moisture which the air can contain varies directly with the temperature, that is, it increases with a rise in temperature and decreases with a fall in temperature. Relative humidity is defined as the ratio between • Assistant Professor of Surgery, Northwestern University Medical School; Director of Anesthesiology and Inhalation Therapy, The Children's Memorial Hospital, Chicago, Illinois
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DAVID ALLAN
the mass of vapor actually present in the atmosphere and the maximum which the atmosphere is capable of holding at a given temperature. Density and buoyancy are important factors which affect the suspension of particles. Density is defined as the ratio of the mass of a body divided by its volume. The lower the temperature of a gas at a constant pressure, the greater its density. Archimedes' principle states that all bodies completely or partially immersed in a fluid are buoyed up by a force equal to the weight of the fluid displaced. Therefore, if the weight of a body is less than the weight of the fluid it displaces, the body will float in the fluid. In considering these factors it is important to realize that gases and fluids are governed by the same laws. Viscosity, defined as the internal friction of resistance to deformation of a fluid, plays the paramount role in determining the laminar flow rate of a substance through a tube. In turbulent flows, the density of the fluid, rather than theyiscosity, plays the important part in determining its volume flowrate. Room air normally has a humidity deficit~ When the air is inspired, the air is warmed from approximately 21 0 C. to 370 C. in the proximal airways. This further increases the humidity deficit, for even if the air were fully saturated at 21 0 C., heating to body temperature would produce a humidity deficit. The muco,us membranes of the nose and to a lesser degree the oropharynx and tracheobronchial tree contain the humidifying mechanism. In an adult, 1 liter of water is used in 24 hours to supply this humidifying mechanism, and there is a relatively higher requirement per square meter of body surface in the child with its higher metabolic rate (Fig. 1). Disease producing pyrexia and increased minute volume further increase the demand. Thus, the cardinal rule is adequate hydration of the patient as a whole. Dehydration will impair tl;tenormal ciliary activity2, 7, 8 and mucus will be retained. The greater the retention of secretions, the greater the culture medium available to propagate harmful bacter~. Any impairment of the humidification mechanism (for example, by an upper respiratory infection or by being bypassed by an endotracheal tube or tracheostomy) will produce retention of secretioIls which are mechanically obstruc" tive and are potential media for bacteria growth. The best method of treatment of an absolute humidity deficit is nebulization. The mechanical nebulizer is the type presently being used and the size of particles produced is determined by its structural design and inlet pressure. Basically, the Ilebulizer cQnsists of a capillary tube partially submerged in the fluid~o be nebulized, and a jet orifice that blasts a gas stream across the tip'of the capillary tube, thereby creating a negative pressure at this point (the Bernoulli principle) and sucking the fluid up the capillary tube. Thejetstrell
RECENT
AnvANCES
IN PEDIATRIC INHALATION THERAPY
1613
Numerous studies of the physical factors which determine the site and quantity of deposition of water particles in the tracheobronchial tree have been published. 6, 9, 20, 21 Particle size largely determines the site of depositionjlo that for the lower bronchi and alveoli is 1 to 3 IL, for intermediate bronchi 3 to 5 IL, and for the trachea and larynx 5 to 8 IL. 20 , 25 Particle sizing is accomplished either by the absolute method3 , 10, 12, 23, 26 or by the Casella Cascade Impactor Method. 4 , 13, f9, 27 Both methods are technically difficult and for this reason many nebu,lizers are released for use on patients without performance data being available Some believe that to deliver particle sizes in the 1 to 3 IL range, it is necessary to include in the stream a percentage of the larger particles, 6 .to 8 IL, which prevent the smaller sizes from "raining out" in the upper respiratory tract, but others believe that the particles should be of a uniform size. The volume of water nebulized per unit time and per unit air flow is important but no scientifically determined specifications existed until the advent of the Herzog nomogram (Fig. 1). H eaJ,ed nebulizers are still being investigated. The principle of the heated nebulizer is that by raising the temperature of the humidity delivered at the patient to body temperature, there will not be a humidity deficit. Thus the temperature at the nebulizer itself must be above body temperature (120° F. in the Puritan) and should be varied in direct proportion to the length of the connecting tubing. The opponents of this technique argue that the air stream is so lightened that there is not sufficient buoyancy to carry the particles far enough down the respiratory tract. In our preliminary investigation we have found the heated nebulizer to be efficacious in the management of the infant with a tracheostomy. This year saw the introduction of the ultrasonic aerosol generator (Fig. 2). The particle size is a direct function of the ultrasonic frequency generatedP It is thus possible to predict and influence the body water balance through the airways. These nebulizers have an efficiency fifteen times greater than the best mechanical ones. They will have an unlimited use in intermittent positive pressure breathing, tracheostomy humidification, and non-rebreathing anesthesia circuits; but in pediatric inhalation therapy, it should be remembered that these nebulizers are very efficient and this efficiency can cause overloading of the circulation if the vaporizer is not regulated with care. One of these generators can nebulize 0.72 grams of physiological saline per minute in a closed circuit. 14 An experimental model designed for open circuit use is said to generate ten times this amount. The ultrasonic aerosol generator is probably the biggest advance in inhalation therapy in a century.
The Pediatric Air Oxygen Aerosol Mist Tent At Children's Memorial Hospital we have developed a pediatric air
DAVID
1614
220
ALLAN
12 DROPS,/Iml'n
11 10
9
~~~
8
7 6
5
4
l \ \\l\ \1\ '\[\l\ 1\ ,\[\
f:\
\1\ 1\ I'\. l~
\1\ I\~ f\.~1'-..1":1'-.. I""'I\~ 1"1'- 1"-1' ~ ~b - - ---[\ t'" 1'.... k'I'1"- l' t-r-j:::: l' t-j::: t-- !:::f::+:::r",1"- t-..,.J'-.. I--=E t:-' ~ 1r-;...: 'I'-1=:: t-I=: I-;-t- r-t= I-t- t-
3
t:::r--
0--=
5
7
t-,.....
\:::
9i11 U ~ U ~.n n VTot I/min
Figure 1. Nomogram for the prediction of the amount of humidity of inspired gas and the net gain of water of the patient at different drop rates to the ultrasonic nebulizer. The intersection between a line drawn from VTot and the drop-rate curve indicates the concentration of humidity as read off on the left-hand ordinate (H20, g!m3VTot). The value read off at the "net gain" ordinate multiplied with the value for alveolar ventilation (VA) in cubic millimeters gives the net gain of water of the patient. VAhas to be calculated as VA = VTot - (VDResP. + VDpat)· The "net gain "ofthenomogram includes the humidity of the standard humidifier of the Engstrom respirator, which gives a humidity of 12 gm. of water per cu. mm. of inspired gas. Room-air humidity is not included. (Herzog, P. et aI., Acta anaesth. scandinav. 8: 79,1964.)
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oxygen aerosol mist tent using an efficient mechanical nebulizer. The requirements that we established were: 1. It should be possible to vary the volume of the tent according to the size of the child, and to raise the side rails of the cribs to their fullest extent. 2. The temperature of the environment of the child should be controllable. 3. Humidification in the tent should be 100 per cent in the micron size 1 to 8 J.I. with no particles over 10 J.I. which would "rain out" and wet the patient. 4. The nebulizer should be driven by oxygen or compressed air. 5. The elimination of CO 2 should be efficient. 6. Everything in contact with the patient should either be disposable or autoclavable. From Figure 3 it can be seen that the tent is adjustable in height and actually is suitable for adult use. Figure 4 demonstrates that the side rails can be fully elevated, and that the temperature of the environment
Figure 2. The Herzog ultrasonic aerosol generator being used in an anesthetic non-rebreathing circuit.
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Fig. 3
Figure 3. The Allan-Walsh pediatric air oxygen aerosol tent showing its versatility in size. Figure 4. The pediatric tent with the side rails fully elevated. The temperature is monitored with a thermometer. Note the dense mist which does not cause a "rainout."
Figure 5. Although the Allan-Walsh pediatric air oxygen aerosol tent is not arecirculating tent, a high flow of 13 liters eliminates C02 accumulation .
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Figure 6. The Allan-Walsh pediatric air oxygen aerosol unit packaged for autoclaving and subsequent storage.
is monitored and controlled. There is no "rain-out," yet the mist is so dense that it is difficult to see the patient. IS The nebulizer can be driven by either compressed air or oxygen. This is an excellent combination for the treatment of cystic fibrosis. The unit is a noncirculating one with a high flow of 13 liters which precludes CO 2 accumulation (Fig. 5). The performance was checked, in the finished product, by actual measurement and found to conform to all the specifications. The canopies are disposable and everything in contact with the patient is autoclavable (Fig. 6). STERILIZATION OF EQUIPMENT
Cross infection with inhalation therapy equipment acting as the carrier has always concerned us. These new air oxygen mist units* have
* Aquastream Mist-O.-Gen Air Oxygen Tents, Mark II, Children's Memorial Hospital (1) Allan-Walsh Model. Supplied by Liquid Carbonic Division of General Dynamics. Canopies, Allan-Walsh design.
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done much to eliminate the potential hazard. They can do the work previously done by oxygen tents, air tents, croupettes, croup tents and Walton humidifiers, and do it much more efficiently. Simplicity of design generally reduces maintenance, and this has proved true in actual use despite the fact that the component parts are autoclavable. Gas sterilization of inhalation therapy equipment leaves much to be desired, for the results are not absolute and the technique is slow and expensive. The slowness necessitates additional equipment. Ideally, all inhalation therapy equipment should be either disposable or autoclavable. This will be difficult to achieve in pediatric inhalation therapy as two of the most important pieces of equipment are incubators and ventilators which are complicated mechanisms constructed, in essential parts, of non-autoclavable materials.
THE INCUBATOR Incubators have proved to be most difficult to sterilize. They evolved from the Hess bed which was fitted with a humidification system. The requirements for environmental control of the infant have been poorly understood. We are still at the "hot box" stage. With great difficulty we have managed to eliminate pathogenic organisms in incubators using culture control to check the efficacy of sterilization techniques. New humidification systems were installed in the older model incubator. All reservoirs are siphoned off after use. New type gaskets were installed making cleaning very much easier. Amphyl* is the sterilizing solution. It is interesting to note that we have multiple oxygen limiters on some of our incubators. It is our belief that the critical factor in the production of retrolental fibroplasia in the premature infant is the p02 of the arterial blood, which should be monitored and limited to normal (100 mm. Hg). The oxygen in the atmosphere should be limited to a range of 30 to 100 per cent depending on the arterial p02 of the infant. The most obvious illustration of this concept is a premature infant with a central arteriovenous shunt. An infant with an oxygen saturation of 25 per cent most certainly will not suffer any sequelae from the use of 100 per cent oxygen in the atmosphere. The main feature of an intensive care incubator should be immediate accessibility of the patient. Both companiest supplying this type of incubator have complied with our wishes. Our intensive care units have become quite elaborate with servo temperature controls and manifolds for electrocardiographic leads, pressure manometric catheters and ventilator hoses.
* Amphyl supplied by Lehn & Fink Products Corporation.
t Supplied by Air Shields and Ohio Chemical.
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INTERMITTENT POSITIVE PRESSURE RESPIRATION (IPPR) IN INFANTS
It has only been in the last three years that it has been possible automatically to ventilate infants satisfactorily. The requirements for an infant ventilator are quite challenging.22 It must be capable of generating variable flows, down to very slow rates, allowing laminar flow, more equal distribution of gases and a lower cycling pressure. The dead space must be extremely low and the resistance to expiratory flow must be controllable and variable to deal with low compliance. The apparatus and connections should be lightweight and sterilizable or disposable. Unfortunately, none is autoclavable. There are two basic types of ventilators available, the volume limited Engstrom and the volume variable Bird Mark 8 and Bennett PR2 with Q circle. In our opinion, normal respiration in the infant is volume variable so that the Bird Mark 8 with Q circle was chosen for the ventilation of our infants. It has proved to be satisfactory but far from perfect, as it, like all ventilators, is of basic adult design. There is a big difference in shifting a volume of 15 cc. and a volume of 500 cc. The Bennett PR2 with Q circle is acceptable if fitted with an expiratory retard mechanism. The timing of its nebulizer is slightly superior to that of the Bird Mark 8 as it preloads the circuit with humidifying particles before inspiration begins. All entrainment mechanisms are notoriously inaccurate. Should there be concern about the possible production of retrolental fibroplasia, the ventilator should be driven by compressed air. The exponents of the volume limited technique insist that it is absolutely necessary to have a constant deliverance of oxygen to the alveoli. The main points of management of intermittent positive pressure breathing have been frequently described.H We have had considerable experience in the management of infants1 and there are several points that require special emphasis and care. By far the most important is the collection and training of a large and dedicated staff as the patients are very ill and are often in precarious condition. They demand a constant watch and frequent attention: any alteration in any parameter must be noted immediately, properly assessed, and any necessary action performed promptly. A team of anesthesiologist, inhalation therapist, cardiologist, surgeon, bronchologist and intensive care nurse must be available 24 hours a day and seven days a week. The improvement in our team has been reflected in the gradual improvement of our salvage rate (in all cases of IPPR including postoperative infants). In approximately one-quarter of our patients, the maintenance of life has been shown to be impossible because of inadequate surgical correction of the defects involved. Along with. an intensively trained team, an intensive monitoring program is necessary. The patient is nursed on an automatically temperature controlled water-alcohol blanket or in a temperature servo controlled
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incubator and kept at any preset desired temperature, recorded and controlled by a thermistor. The electrocardiograph is continually demonstrated by oscilloscope with an alarm system to warn immediately of the occurrence of bradycardia. The respirator settings initially required are noted and alterations made as compliance varies, as indicated by a change in respiratory time. Normal spirometers such as the Wright are unsuitable for infants as the air flow is too small to drive the vanes. Weare introducing to our armamentarium a servo spirometer with an accuracy to 2 cc. to overcome this problem. The alveolar CO 2 can be monitored as an additional aid, using a Beckman 190 gas analyzer. The most important parameters to be monitored are the arterial pH, pC02, p02 and oxygen saturation. There is a risk of complications in leaving an arterial catheter in an infant, but it is one that should be accepted. A capillary technique is unsuitable as the infants are usually in peripheral vasoconstriction. Standard bicarbonate and plasma electrolytes are measured daily. We are attempting to introduce a thermistor cardiac output technique which should be a great aid in the management of the infant during IPPR. Initially, respiration is controlled, but patient cycling is allowed when a suitable rate is established. Tachypnea is almost constant initially and tends to recur whenever ventilation is reduced for any reason, so that control frequently has to be re-established. The initial settings produce hyperventilation as patients have respiratory acidosis. Control is usually achieved at arterial pC0 2 leveis of 20 to 30 mm. Hg, pH 7.4 to 7.5. Subsequent adjustments to respiratory rates and volumes in an attempt to maintain these levels are made on clinical judgment, published nomograms giving only a very rough indication of requirements in this size of patient. Values in many patients with partially corrected cyanotic heart disease are variable, however, and can only be used to judge the progress of that particular case. The use of tromethamine (THAM) has greatly aided in the management of the cyanotic infant, but complicates the respiratory biochemical control. The major problem in the management of infants undergoing IPPR is the maintenance of an adequate airway. Tracheostomy in an infant carries with it a considerable death rate (30.7 per cent).15 The main causes for this, other than basic underlying pathology, are inadequate humidification following the bypassing of the normal humidifying mechanism and poor suction technique. Results following the use of the ultrasonic aerosol generator in such patients are being awaited with great interest. An absolutely sterile technique of suctioning is essential-sterile gloves, catheters, and washing water for each suction; therefore, at least two nurses must be present. Speed is also important, so that one nurse disconnects the ventilator while the other puts the suction catheter into the trachea, allowing suction only on withdrawal, giving only one suction at a time, and allowing a few minutes of IPPR in between. The automatic monitor with
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an alarm system (Electrodyne) has been found to be life-saving in giving warning of bradycardia during suctioning. Segal has developed an ingenious method for overcoming bradycardia during suctioning. 24 This method allows for suctioning during the inspiratory cycle of the ventilator. Endobronchial suction is given as one or the other lung shows signs of obstruction. It may be accomplished under direct vision or an angulated suction catheter may be used." In patients who are fit enough, suction is preceded by use of a bronchodilator, percussion and postural drainage. Frequency of suction is reduced as soon as possible to hourly or two hourly intervals to minimize the possibility of tracheal trauma and introduction of infection. Bronchoscopic suction is required for the removal of large and viscous plugs-often repeatedly in the same patient. Antibiotic cover is essential, but, despite this, gross infection is not infrequently the major cause of death. The new Great Ormond Street tracheostomy tube* designed by Ian Aberdeen is an excellent tube for use with a ventilator. It has a single lumen with its orifice funnel shaped to accept the ventilator connection. The correct selection of a size for the trachea dispenses with cuffs which can slip off. There may be some leak, which can be compensated for by the ventilator. Every effort is made to end IPPR as early as possible, allowing periods of spontaneous respiration of increasing length according to the infant's capacity. IPPR of an infant is difficult, management of the airway most challenging, but success most rewarding. PHARMACOLOGY
Progress in the pharmacology of inhalation therapy has on the whole been rather disappointing. Infants cannot manage sodium chloride as well as children or adults so that sterile water, in spite of its irritant properties, should be used in preference to saline for humidification. Isoproterenol is still the best bronchodilator. It must be ruefully admitted that water, saline and isoproterenol are the only proven efficacious aerosol pharmacologic agents in inhalation therapy. Our knowledge of the effects of oxygen has increased from the stimulus of the use of hyperbaric oxygenation. HYPERBARIC OXYGENATION
Professor Illingworth of Glasgow very aptly and succinctly described the present status of hyperbaric oxygenation, in words to the effect that much research was still to be done in basic physiology, pharmacology and
* S. Smith & Sons (Canada)
Ltd., distributors.
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DAVID ALLAN
pathology before the overall place of hyperbaric oxygenation in our therapeutic armamentarium could be assessed. Oxygen under from one to four atmospheres has been investigated as a therapeutic agent in Scotland, H011and and America. Hyperbaric oxygenation at one to two atmospheres is the treatment of choice of carbon monoxide poisoning. The patients are placed in mobile chambers, and in 20 minutes the vast majority are awake and well. Other conditions such as tetanus infections produced by anaerobic organisms, infections produced by aerobic organisms, and cyanotic heart disease are in the process of being investigated.
SUMMARY
Pediatric inhalation therapy has taken a great surge forward in recent years. The outstanding achievements are in nebulization, sterilization, intermittent positive pressure breathing especially in the infant, and hyperbaric oxygenation. A great deal of research is being conducted in this field and much is expected of this form of therapy in the future.
REFERENCES 1. Allan, D. and Kay, B.: Management of infants with postoperative respiratory distress. Submitted for publication. 2. Bellenger, J. J.: A study of ciliary activity in the respiratory tract of animals. Ann. Otol. Rhin., & Laryng. 68: 351, 1949. 3. Bennett, A. H., Osterbert, H., Jupnik, H. and Richards, O. W.: Phase Microscopy, Principles and Applications. New York, John Wiley & Sons, 1951. . 4. British Standard 28, 1957. 5. Bush, G. H.: Tracheobronchial suction in infants and children. Brit. J. Anaesth. 36: 322, 1963. 6. Cushing, J. E. and Miller, W. F.: Considerations in humidification by nebulization. Dis. Chest 34: 388, 1958. 7. Dalham, T.: Mucus flow and ciliary activity in the trachea of healthy rats and rats exposed to respiratory irritant gases. Acta physiol. s(',sndinav. S3: Suppl. 123, 1956. 8. Dalham, T.: Studies of the effect of sulphur dioxide on ciliary activity in rabbit trachea in vivo and in vitro and on the resortional capacity of the nasal cavity. Am. Rev. Resp. Dis. 83: 566, 1961. 9. Dantrebande, L.: Studies on aerosols. University of Rochester Atomic Energy Project, UR 530, October, 1958. 10. Fuchs, N. and Petryanoff, J.: Nature 138: 111, 1937. 11. Gilston, A.: Management of respiratory distress after cardiothoracic surgery. Thorax 17: 139, 1962. 12. Green, H. L.: Some accurate methods of determining numbers and size-frequency of particles in dust. J. Indust. Hyg. 16: 29,1934. 13. Green, H. L. and Watson, H. H.: Unpublished Report, Particle Clouds, p. 304 E & FN, Sponlid, London, 1957. 14. Herzog, P., Norlander, O. P. and Engstrom, C. G.: illtrasonic generation of aerosol for the humidification of inspired gases during volume controlled ventilation. Acta anaesth. scandinav. 8: 79, 1964.
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15. Holinger, P., Brown, W. and Maurizi, D.: Tracheostomy in the newborn. Accepted for publication, Pediatrics. 16. Lovejoy, F. W., Constantine, H. and Dantrebande, L.: Importance of particle size in aerosol therapy. Proc. Soc. Exper. BioI. & Med. 103: 836, 1960. 17. Matausechck, J.: Einfuhrung in die Ultraschalltechnik. August, 1961, VED, Urlag Tech., Berlin. 18. Matthews, L. W., Doershuk, C. F., Wise, M., Eddy, G., Nudleman, H. and Spector, S.: A Therapeutic Regimen for Patients with Cystic Fibrosis. Department of Pediatrics, Western Reserve University School of Medicine, Cleveland, Ohio. 19. May, K. R.: J. Scientific Instr. es: 187, 1945. 20. Mitchell, R. I. : Retention of aerosol particles in the respiratory tract. A review. Am. Rev. Resp. Dis. 8S: 627, 1960. 21. Morrow, P. E.: Physical and physiological factors controlling fate of inhaled substances. Proc. 4th Ann. Meet. on Bio-Assay and Analytical Chemistry. AEC Research and Development Report, Washington 1023, Nov., 1958. 22. Mushin, W. W. and Mapleson, W. W.: Problems of automatic ventilation in infants and children. Brit J. Anaesth. 34: 516, 1962. 23. Salem, H. and Cullumbine, H.: Toxicology and Applied Pharmacology, Vol. 2. 1950, pp. 183-187. 24. Segal, S.: Personnal communication. 25. Shwachman, H.: Therapy of cystic diseases of the pancreas. Pediatrics e5: 1551, 1960. 26. U.S. Public Health Service, Public Health Monograph 959, No. 60. 27. University of Michigan, Encyclopedia of Instrumentation for Industrial Hygiene. Ann Arbor, Michigan, 1956, pp. 142 and 178. 707 Fullerton Avenue Chicago, Illinois 60614