- Email: [email protected]
CONTINUOUS CONTROLLED HUMIDIFICATION OF INSPIRED AIR
1214 tests
demonstrated
severe
delayed hypersensitivity
at 48-72
"
General Clinical Research Centers Branch, National Institutes of no. P.F. 330 from the American Cancer Society, Inc., a grant from the National Foundation, and the maternal and infant care project no 515, Dade County, Florida. The foetal tissue bank at the RoyaJ Marsden Hospital is supported by a grant from the Medical Research Council.
Health, grant
W. W. CLEVELAND M.D.
B. Department of Pediatrics, School of Medicine, University of Miami,
M.D.
Florida 33152
London S.W.3
J. FOGEL
W. T. BROWN M.D.
Department of Clinical Pathology, Royal Marsden Hospital, 11.
M.D.
H. E. M. KAY Lond., M.R.C.P., F.C. PATH.
A. J. S., Festenstein, H., Leuchars, E., Wallis, V. J., Doenhoff, Lancet, 1968, i, 183. 12. Miller, J. F. A. P., Osoba, D. Physiol. Rev. 1967, 47, 437. 13. Cooper, M. D., Peterson, R. D. A., Good, R. A. J. Pediat. 1965, 67, 907. 14. Cleveland, W. W., Fogel, B. J., Kay, H. E. J. clin. Invest. 1968, 47, 20a.
Davies, M. J.
CONTINUOUS CONTROLLED HUMIDIFICATION OF INSPIRED AIR
re-
hours. This response was to the first application after transplant and approximately 3 months after previous tests. It is probable that small amounts of the chemicals remained in the tissues and when thymic function was established, sensitisation occurred. Biopsy of a lymph-node 8 months after implantation of thymic tissue was normal for an infant of this age (fig. 4b). This finding, coupled with normal numbers of circulating lymphocytes, indicated repopulation of peripheral lymphoid tissue with small lymphocytes. After operation lymphocytes grew well in culture in response to P.H.A. Although the donor was female, no XX cells were identified in extensive examination of circulating lymphocytes and lymph-nodes. The first blood was not studied until 3 weeks after transplant, therefore a transient circulation of donor thymic cells might not have been detected. Nevertheless, these observations show that the major part, at least, of the repopulation of peripheral lymphoid tissues was from host rather than donor cells. This is in contrast to the findings in experimental animals 11 but because of differences in species, timing, and cell numbers there is not necessarily any conflict. The rapid response of the peripheral blood lymphocytes in this case certainly suggests a humoral mechanism, but an alternative intermediary role of the thymus, whereby the thymic milieu enables bone-marrow stem-cells to develop into immunologically competent " reactor " cells, is by no means excluded.3 12 Thus, it seems that immunological function has been successfully reconstituted by transplant of foetal thymic tissue in an infant having an isolated congenital absence of the thymus. In addition to the therapeutic potential established, the information gained from this study contributes to understanding of thymic function in man. Cooper et al. have proposed a two-compartment " system in which cellular immunity depends upon action of the thymus. Circulating immunoglobulins are thought to depend on activity of plasma-cells which function independently of thymus and are derived from a separate The source probably in the gastrointestinal tract.13 findings in our patient generally support such a concept. This case has been reported, in abstract, elsewhere." We thank Dr. Robert A. Good and Dr. Angelo DiGeorge for their interest and advice, Dr. W. Dean Warren and Dr. John Fomon for their surgical assistance, Dr. Gilbert Chang, Dr. Doralys Arias, and Dr. George Smith for chromosome studies, Dr. Hilaire Meuwissen for special lymphocyte studies, Dr. Agustin Castellanos for radiographic studies, Dr. M. J. G. Allen for assistance in the fcetal tissue bank, and Dr. John A. May for referring the patient. This work was supported by grant no. FR-0261-03 from the
action, maximal
It has been observed that gases can be administered through the nose at high flow-rates provided that they are at body-temperature and fully saturated with water-vapour. A simple and easily portable system has been devised for delivering gases in this way, and has been shown to be effective in volunteers. It is now proving satisfactory in clinical use, both for continuous humidification and for administration of oxygen. Summary
INTRODUCTION
MOST methods of humidifying gases for inhalation rely on the addition of water in droplet form. This is usually done by high-pressure jet nebulisation, by ultrasonic transducers, or by spinning discs. Nebulisers are useful for the transport of drugs to the airways, but have a number of disadvantages as humidifiers.l Most notable are the difficulties in controlling water content (and intake by the patient), particle size, and the concentration of solute. In addition it is usually necessary to use a mask, hood, or tent to ensure that the desired concentration of aerosol reaches the patient. Most of the problems of humidification could be solved by the use of water-vapour instead of aerosols. This would more nearly reproduce the physiological mechanism of humidification in the respiratory tract. Such a method became practicable when the author discovered that gases could be blown into one nostril at 20-30 litres per minute without discomfort, and even without perception, provided that the gas was at body-temperature and 100% saturated with water-vapour. (The highest tolerable flow of dry, cool gas is normally regarded as 6-8 litres per minute.) PRINCIPLE
of the new method is that, since the water content of the gas is determined by the temperature, the humidity of the inspired gas can be regulated by alterations in temperature. Provided that the flow into the nostril is in the range of the peak inspiratory flow, the inspired air will consist only of the gas blown into the nostril, even if the patient breathes with his mouth open. The nasopharynx and mouth will act like an anxsthetic Y-piece, with the other nostril constituting a safety outlet. Because the air is saturated with water-vapour there will be no evaporation of water from the The vapour administered is not mucus in the airways. deposited in the airways, so the secretions remain unaltered. During quiet breathing, peak inspiratory flow-rates are about 30-40 litres per minute, so this would be the theoretical flow into the nostril if the gas was to be 100% saturated. In practice, however, normal inspired air is only 75% body humidity, and since the aim is to reproduce only the physiological situation, there is no need for such high flow-rates. The
principle
SYSTEM
The connecting system between patient and humidifier is made of light-weight flexible tubing. From the humidifier a polyethylene-foil tube (length 130 cm., diameter 2 cm., wall thickness 0-05 mm.) leads to the patient’s chin. From the chin a flexible P.v.c. tube (12 mm. diameter) leads round the ear to the nose (fig. 1). About 1 cm. of this projects into the nostril, and this part has a nylon-foam collar to prevent room air from being drawn in by the Venturi effect. We use a spherical, translucent, autoclavable humidifier (’ Hygrotherm’) made of polycarbonate, with a 250-watt heating coil (fig. 2). The temperature of the humidifier is controlled by a thermistor in the nose-piece. Between 32°C and 400C temperature can be controlled within 0.5°C. If a fault develops in the system, the heating element is automatically disconnected. Gas passes 1.
Cushing, I. E., Miller, W. F. in Respiratory Therapy (edited by P. Safar); p. 169. Philadelphia, 1965.
1215
Fig. 2-Equipment for nasal humidification. Fig. 1-Plastic foil tube and nose-piece in
projects
into the
use.
The thermistor lead
nose-piece.
through the humidifier and takes up water-vapour. Some of this condenses in the tubes, and this condensation near the nose-piece is evidence that the gas is 100% saturated on reaching the patient. The liquid tends to collect in the polyethylene foil, but this problem has been solved by placing a Venturi at the inlet of the humidifier, and connecting it to a thin tube within the foil tube. By this means the condensed water is returned to the humidifier. (When the humidifier is used with a respirator the Venturi must be disconnected.) EXPERIMENTAL EVALUATION
An indirect assessment of the efficiency of the system was made from experiments on eleven volunteers. After topical cocaine anaesthesia a thin rubber catheter
Fig. 3-Effect
of variations in tracheal air.
11 normal
subjects. Oxygen
admixture of o
=
Nose
gas-flow
room
on
concentrations indicate
0 = Mouth
introduced via the nose to the trachea. Oxygen saturated with water-vapour at 37°C was blown into one nostril at flow-rates from 5-30 litres per minute. At each selected flow-rate, subjects were instructed first to breathe with mouth closed and then with their mouths wide open (fixed with a McKesson prop). Samples of inspired air were taken from the trachea during nasal and mouth breathing. Po2 was measured with an oxygen electrode (’ Radiometer’) and the percentage of oxygen in each sample was calculated. The results are recorded in fig. 3. The performance of the humidifier is shown in fig. 4. Because pure O2, saturated with water-vapour, was administered, these determinations from tracheal air/gas samples are a measure of the admixture of room air, or, alternatively, a measure of the quantity of saturated gas that reaches the trachea from the humidification system. During nasal breathing high oxygen concentrations were found in all cases, reflecting high humidity (above 38% oxygen at 5 litres per minute flow, and above 78% at 30 litres per minute). Mouth breathing, as expected, increased room-air admixture, but mean oxygen concentrations of 35-60% were maintained. In two subjects little gas reached the trachea during mouth breathing. One hyperventilated to such an extent that he developed a degree of respiratory alkalosis sufficient to cause carpopedal spasm. The other had a very narrow was
percentage of oxygen in
air.
breathing.
(1) Humidifier. (2) Venturi. (3) Foil tube containing thin suction tube. (4) Temperature-control box.
breathing.
degree
of
Fig. 4-Performance of humidifier.
Temperatures at each gas-flow rate were measured when air temperature at patient had been stabilised at 37cC (room temperature=22°C).
1216 passage. A further variable which may well influence admixture was observed: the position of the soft palate may be changed involuntarily, and the nasopharyngeal tract either enlarged or reduced as a result.
naso-pharyngeal
CLINICAL USE
We have used nasal humidification routinely postoperatively in patients liable to pulmonary complications. In three patients the system has been used for postoperative analgesia with humidified nitrous oxide, oxygen, and air. When improved oxygenation is the aim, flow-rates of 15-30 litres per minute are used. We have found that with flow-rates of this order airway secretions may become too thin and watery, but this can be prevented by lowering the gas temperature to 5°C below body-temperature.2 When improved humidification is required, the gas is kept at body-temperature, and the flow regulated according to the clinical impression of the effect on secretions. HAZARDS
Strict control of the temperature of the gas is essential. If the heating element is not switched on, excessive drying of the airway secretions will result. If the temperature rises too high, there is danger of scalding, with damage to cilia. With our automatic system the main risks are: (a) that the gas-flow is discontinued while the humidifier is switched on, and (b) that the gas-flow is increased by more than 5 litres per minute at one time. Either would result in a transient, but dangerous, increase in the temperature of the gas reaching the patient. The humidifier may be obtained after February, 1969, from Simonsen and Weel, Albertslund, Denmark. Separate foil tubes and nose-pieces may be obtained from Polystan, Herlev, Denmark. Department of Anæsthesia, Rigshospitalet, Copenhagen, Denmark
NIELS LOMHOLT M.D.
Copenhagen
EXTRACORPOREAL LIVER PERFUSION USING A NEW PERFUSION CHAMBER A technique of extracorporeal liver perfusion for the treatment of hepatic coma of capable maintaining liver viability for many hours was developed. A new liver chamber was designed to reproduce the physiological environment of a normal liver. Within this sealed chamber the extracorporeal liver rests on a plastic diaphragm which is subjected to intermittent positive pressure, thus simulating normal respiratory movements. An advanced perfusion circuit, composed largely of disposable parts, forms a compact and closed system. In addition to reproducing physiological conditions, the apparatus has several other important advantages, for normothermic perfusions, for the treatment of hepatic failure, and for hypothermicperfusion preservation of livers intended for trans-
Summary
plantation. INTRODUCTION
EXTRACORPOREAL liver perfusion for the treatment of hepatic coma was first used simultaneously by Eiseman in the U.S.A. and by Sen in India in 1964. The method has since been adopted elsewhere 3-6 and is now used in several centres in Britain and Europe. 2. 3. 4.
5. 6.
Lomholt, N., Cooke, R., Lunding, M. Br. J. Anœsth. 1968, 40, 335. Norman, J. C., Saravis, C. A., Brown, M. E., Akroyd, F. W., McDermott, W. V.J. surg. Res. 1966, 6, 121. Watts, J. McK., Douglas, M. C., Dudley, A. A. F., Gurr, F. W., Owen, J. A. Br. med. J. 1967, ii, 341. Romieu, C. Personal communication. Pirola, R. C., Ham, J. M., Elmslie, R. G. Med. J. Aust. 1968, i, 891.
We have been working on this technique for the past In our first series of over 50 experiments we developed a technique for prolonged perfusion of the pig liver.’8 In the second series of 14 experiments the isolated pig liver was used to provide temporary hepatic 9 support for calves with experimental liver failure. Recently the extracorporeal pig liver was used on seven occasions for the treatment of 4 patients in hepatic coma.lo In the course of this experience a new liver-perfusion chamber was designed and a technique evolved which is safe and simple, and effective for many hours of perfusion. two years.
MATERIALS AND METHODS
Preparation of the Patient On the day before perfusion
an indwelling arteriovenous Silastic’ shunt is constructed using the largest possible ’ Teflon ’ cannulx. In adults the brachial artery and the basilic vein are used, but in children and small women the superficial femoral artery and the long saphenous vein are more suitable. On the day of perfusion the patient’s clinical, hamatological, and biochemical state is fully assessed. Previous conservative treatment is continued, and every attempt is made to correct any anaemia, hypoglycxmia, hypovolxmia, and electrolyte and acid-base imbalance. Just before perfusion blood-samples are taken for culture and for subsequent immunological studies. During perfusion the pulse, blood-pressure, central venous pressure, electrocardiogram, temperature, blood pH, bloodsugar, and plasma-electrolytes are monitored frequently. Preparation of the Animal 24-36 hours before perfusion two pigs (40-70 lb. [18-30 kg.] according to the size of the patient) are isolated and fed on a light diet with sugar-water and vitamin-E supplements. Intramuscular ampicillin is given. Just before use, one animal is hosed down and scrubbed, the other being kept as a standby. Preparation of the Liver Details of anxsthesia and hepatectomy have been given elsewhere,l5 and only important points will be mentioned here. Throughout hepatectomy extreme care is taken in handling the liver and the bowel. The animal is given intravenous dextran 40 injection (’ Rheomacrodex’) in dextrose, bicarbonate, and heparin to maintain an adequate bloodpressure, to ensure good hepatic perfusion, to maintain liver glycogen stores, and to counteract any metabolic acidosis. The liver is removed, and the portal vein and hepatic artery are rapidly cannulated with Redding’ left-atrial cannulx. The organ is then cooled and washed free of its blood with 8 litres of specially prepared balanced electrolyte solutionat 15°C. The suprahepatic vena cava and the common bileduct are cannulated, and a temperature probe is placed in the infrahepatic vena cava. The cooled asanguineous liver, with all its cannulx clamped, is transported to the perfusion apparatus which has already been assembled at the patient’s side in the ’
perfusion room. The Liver-perfusion Chamber We have found that prolonged liver perfusion is most successful when the physical environment of the extracorporeal liver is similar to that in the living animal. The liver chamber which we use was designed to simulate as closely as possible the normal physiological conditions. The chamber consists of three components: the outer container, the liver diaphragm, and the lid. The outer container is a stainless-steel cylinder, 10 in. (25 cm.) in diameter and 6 in. (15 cm.) high (fig. 1). Round its open top is welded a flange 2 in. (5 cm.) wide and 1 in. (2-5 cm.) high, which has eight equally spaced slots to receive corresponding studs from the metal ring of the liver diaphragm. On one side of the 7. Abouna, G. M., Ashcroft, T., Dale, G., Hull, C., Kirkley, J., Walder, D. N. Br. J. Surg. 1968, 55, 388. 8. Abouna, G. M. ibid. p. 761. 9. Abouna, G. M., Ashcroft, T., Muckle, J. T., Hull, C., Skillen. A., Kirkley, J. Br. J. Surg. 1968, 55, 862. G. M., Kirkley, J., Hull, C., Walder, D. N. Lancet, Aug. 31, 1968, p. 509.
10. Abouna,
demonstrated
severe
delayed hypersensitivity
at 48-72
"
General Clinical Research Centers Branch, National Institutes of no. P.F. 330 from the American Cancer Society, Inc., a grant from the National Foundation, and the maternal and infant care project no 515, Dade County, Florida. The foetal tissue bank at the RoyaJ Marsden Hospital is supported by a grant from the Medical Research Council.
Health, grant
W. W. CLEVELAND M.D.
B. Department of Pediatrics, School of Medicine, University of Miami,
M.D.
Florida 33152
London S.W.3
J. FOGEL
W. T. BROWN M.D.
Department of Clinical Pathology, Royal Marsden Hospital, 11.
M.D.
H. E. M. KAY Lond., M.R.C.P., F.C. PATH.
A. J. S., Festenstein, H., Leuchars, E., Wallis, V. J., Doenhoff, Lancet, 1968, i, 183. 12. Miller, J. F. A. P., Osoba, D. Physiol. Rev. 1967, 47, 437. 13. Cooper, M. D., Peterson, R. D. A., Good, R. A. J. Pediat. 1965, 67, 907. 14. Cleveland, W. W., Fogel, B. J., Kay, H. E. J. clin. Invest. 1968, 47, 20a.
Davies, M. J.
CONTINUOUS CONTROLLED HUMIDIFICATION OF INSPIRED AIR
re-
hours. This response was to the first application after transplant and approximately 3 months after previous tests. It is probable that small amounts of the chemicals remained in the tissues and when thymic function was established, sensitisation occurred. Biopsy of a lymph-node 8 months after implantation of thymic tissue was normal for an infant of this age (fig. 4b). This finding, coupled with normal numbers of circulating lymphocytes, indicated repopulation of peripheral lymphoid tissue with small lymphocytes. After operation lymphocytes grew well in culture in response to P.H.A. Although the donor was female, no XX cells were identified in extensive examination of circulating lymphocytes and lymph-nodes. The first blood was not studied until 3 weeks after transplant, therefore a transient circulation of donor thymic cells might not have been detected. Nevertheless, these observations show that the major part, at least, of the repopulation of peripheral lymphoid tissues was from host rather than donor cells. This is in contrast to the findings in experimental animals 11 but because of differences in species, timing, and cell numbers there is not necessarily any conflict. The rapid response of the peripheral blood lymphocytes in this case certainly suggests a humoral mechanism, but an alternative intermediary role of the thymus, whereby the thymic milieu enables bone-marrow stem-cells to develop into immunologically competent " reactor " cells, is by no means excluded.3 12 Thus, it seems that immunological function has been successfully reconstituted by transplant of foetal thymic tissue in an infant having an isolated congenital absence of the thymus. In addition to the therapeutic potential established, the information gained from this study contributes to understanding of thymic function in man. Cooper et al. have proposed a two-compartment " system in which cellular immunity depends upon action of the thymus. Circulating immunoglobulins are thought to depend on activity of plasma-cells which function independently of thymus and are derived from a separate The source probably in the gastrointestinal tract.13 findings in our patient generally support such a concept. This case has been reported, in abstract, elsewhere." We thank Dr. Robert A. Good and Dr. Angelo DiGeorge for their interest and advice, Dr. W. Dean Warren and Dr. John Fomon for their surgical assistance, Dr. Gilbert Chang, Dr. Doralys Arias, and Dr. George Smith for chromosome studies, Dr. Hilaire Meuwissen for special lymphocyte studies, Dr. Agustin Castellanos for radiographic studies, Dr. M. J. G. Allen for assistance in the fcetal tissue bank, and Dr. John A. May for referring the patient. This work was supported by grant no. FR-0261-03 from the
action, maximal
It has been observed that gases can be administered through the nose at high flow-rates provided that they are at body-temperature and fully saturated with water-vapour. A simple and easily portable system has been devised for delivering gases in this way, and has been shown to be effective in volunteers. It is now proving satisfactory in clinical use, both for continuous humidification and for administration of oxygen. Summary
INTRODUCTION
MOST methods of humidifying gases for inhalation rely on the addition of water in droplet form. This is usually done by high-pressure jet nebulisation, by ultrasonic transducers, or by spinning discs. Nebulisers are useful for the transport of drugs to the airways, but have a number of disadvantages as humidifiers.l Most notable are the difficulties in controlling water content (and intake by the patient), particle size, and the concentration of solute. In addition it is usually necessary to use a mask, hood, or tent to ensure that the desired concentration of aerosol reaches the patient. Most of the problems of humidification could be solved by the use of water-vapour instead of aerosols. This would more nearly reproduce the physiological mechanism of humidification in the respiratory tract. Such a method became practicable when the author discovered that gases could be blown into one nostril at 20-30 litres per minute without discomfort, and even without perception, provided that the gas was at body-temperature and 100% saturated with water-vapour. (The highest tolerable flow of dry, cool gas is normally regarded as 6-8 litres per minute.) PRINCIPLE
of the new method is that, since the water content of the gas is determined by the temperature, the humidity of the inspired gas can be regulated by alterations in temperature. Provided that the flow into the nostril is in the range of the peak inspiratory flow, the inspired air will consist only of the gas blown into the nostril, even if the patient breathes with his mouth open. The nasopharynx and mouth will act like an anxsthetic Y-piece, with the other nostril constituting a safety outlet. Because the air is saturated with water-vapour there will be no evaporation of water from the The vapour administered is not mucus in the airways. deposited in the airways, so the secretions remain unaltered. During quiet breathing, peak inspiratory flow-rates are about 30-40 litres per minute, so this would be the theoretical flow into the nostril if the gas was to be 100% saturated. In practice, however, normal inspired air is only 75% body humidity, and since the aim is to reproduce only the physiological situation, there is no need for such high flow-rates. The
principle
SYSTEM
The connecting system between patient and humidifier is made of light-weight flexible tubing. From the humidifier a polyethylene-foil tube (length 130 cm., diameter 2 cm., wall thickness 0-05 mm.) leads to the patient’s chin. From the chin a flexible P.v.c. tube (12 mm. diameter) leads round the ear to the nose (fig. 1). About 1 cm. of this projects into the nostril, and this part has a nylon-foam collar to prevent room air from being drawn in by the Venturi effect. We use a spherical, translucent, autoclavable humidifier (’ Hygrotherm’) made of polycarbonate, with a 250-watt heating coil (fig. 2). The temperature of the humidifier is controlled by a thermistor in the nose-piece. Between 32°C and 400C temperature can be controlled within 0.5°C. If a fault develops in the system, the heating element is automatically disconnected. Gas passes 1.
Cushing, I. E., Miller, W. F. in Respiratory Therapy (edited by P. Safar); p. 169. Philadelphia, 1965.
1215
Fig. 2-Equipment for nasal humidification. Fig. 1-Plastic foil tube and nose-piece in
projects
into the
use.
The thermistor lead
nose-piece.
through the humidifier and takes up water-vapour. Some of this condenses in the tubes, and this condensation near the nose-piece is evidence that the gas is 100% saturated on reaching the patient. The liquid tends to collect in the polyethylene foil, but this problem has been solved by placing a Venturi at the inlet of the humidifier, and connecting it to a thin tube within the foil tube. By this means the condensed water is returned to the humidifier. (When the humidifier is used with a respirator the Venturi must be disconnected.) EXPERIMENTAL EVALUATION
An indirect assessment of the efficiency of the system was made from experiments on eleven volunteers. After topical cocaine anaesthesia a thin rubber catheter
Fig. 3-Effect
of variations in tracheal air.
11 normal
subjects. Oxygen
admixture of o
=
Nose
gas-flow
room
on
concentrations indicate
0 = Mouth
introduced via the nose to the trachea. Oxygen saturated with water-vapour at 37°C was blown into one nostril at flow-rates from 5-30 litres per minute. At each selected flow-rate, subjects were instructed first to breathe with mouth closed and then with their mouths wide open (fixed with a McKesson prop). Samples of inspired air were taken from the trachea during nasal and mouth breathing. Po2 was measured with an oxygen electrode (’ Radiometer’) and the percentage of oxygen in each sample was calculated. The results are recorded in fig. 3. The performance of the humidifier is shown in fig. 4. Because pure O2, saturated with water-vapour, was administered, these determinations from tracheal air/gas samples are a measure of the admixture of room air, or, alternatively, a measure of the quantity of saturated gas that reaches the trachea from the humidification system. During nasal breathing high oxygen concentrations were found in all cases, reflecting high humidity (above 38% oxygen at 5 litres per minute flow, and above 78% at 30 litres per minute). Mouth breathing, as expected, increased room-air admixture, but mean oxygen concentrations of 35-60% were maintained. In two subjects little gas reached the trachea during mouth breathing. One hyperventilated to such an extent that he developed a degree of respiratory alkalosis sufficient to cause carpopedal spasm. The other had a very narrow was
percentage of oxygen in
air.
breathing.
(1) Humidifier. (2) Venturi. (3) Foil tube containing thin suction tube. (4) Temperature-control box.
breathing.
degree
of
Fig. 4-Performance of humidifier.
Temperatures at each gas-flow rate were measured when air temperature at patient had been stabilised at 37cC (room temperature=22°C).
1216 passage. A further variable which may well influence admixture was observed: the position of the soft palate may be changed involuntarily, and the nasopharyngeal tract either enlarged or reduced as a result.
naso-pharyngeal
CLINICAL USE
We have used nasal humidification routinely postoperatively in patients liable to pulmonary complications. In three patients the system has been used for postoperative analgesia with humidified nitrous oxide, oxygen, and air. When improved oxygenation is the aim, flow-rates of 15-30 litres per minute are used. We have found that with flow-rates of this order airway secretions may become too thin and watery, but this can be prevented by lowering the gas temperature to 5°C below body-temperature.2 When improved humidification is required, the gas is kept at body-temperature, and the flow regulated according to the clinical impression of the effect on secretions. HAZARDS
Strict control of the temperature of the gas is essential. If the heating element is not switched on, excessive drying of the airway secretions will result. If the temperature rises too high, there is danger of scalding, with damage to cilia. With our automatic system the main risks are: (a) that the gas-flow is discontinued while the humidifier is switched on, and (b) that the gas-flow is increased by more than 5 litres per minute at one time. Either would result in a transient, but dangerous, increase in the temperature of the gas reaching the patient. The humidifier may be obtained after February, 1969, from Simonsen and Weel, Albertslund, Denmark. Separate foil tubes and nose-pieces may be obtained from Polystan, Herlev, Denmark. Department of Anæsthesia, Rigshospitalet, Copenhagen, Denmark
NIELS LOMHOLT M.D.
Copenhagen
EXTRACORPOREAL LIVER PERFUSION USING A NEW PERFUSION CHAMBER A technique of extracorporeal liver perfusion for the treatment of hepatic coma of capable maintaining liver viability for many hours was developed. A new liver chamber was designed to reproduce the physiological environment of a normal liver. Within this sealed chamber the extracorporeal liver rests on a plastic diaphragm which is subjected to intermittent positive pressure, thus simulating normal respiratory movements. An advanced perfusion circuit, composed largely of disposable parts, forms a compact and closed system. In addition to reproducing physiological conditions, the apparatus has several other important advantages, for normothermic perfusions, for the treatment of hepatic failure, and for hypothermicperfusion preservation of livers intended for trans-
Summary
plantation. INTRODUCTION
EXTRACORPOREAL liver perfusion for the treatment of hepatic coma was first used simultaneously by Eiseman in the U.S.A. and by Sen in India in 1964. The method has since been adopted elsewhere 3-6 and is now used in several centres in Britain and Europe. 2. 3. 4.
5. 6.
Lomholt, N., Cooke, R., Lunding, M. Br. J. Anœsth. 1968, 40, 335. Norman, J. C., Saravis, C. A., Brown, M. E., Akroyd, F. W., McDermott, W. V.J. surg. Res. 1966, 6, 121. Watts, J. McK., Douglas, M. C., Dudley, A. A. F., Gurr, F. W., Owen, J. A. Br. med. J. 1967, ii, 341. Romieu, C. Personal communication. Pirola, R. C., Ham, J. M., Elmslie, R. G. Med. J. Aust. 1968, i, 891.
We have been working on this technique for the past In our first series of over 50 experiments we developed a technique for prolonged perfusion of the pig liver.’8 In the second series of 14 experiments the isolated pig liver was used to provide temporary hepatic 9 support for calves with experimental liver failure. Recently the extracorporeal pig liver was used on seven occasions for the treatment of 4 patients in hepatic coma.lo In the course of this experience a new liver-perfusion chamber was designed and a technique evolved which is safe and simple, and effective for many hours of perfusion. two years.
MATERIALS AND METHODS
Preparation of the Patient On the day before perfusion
an indwelling arteriovenous Silastic’ shunt is constructed using the largest possible ’ Teflon ’ cannulx. In adults the brachial artery and the basilic vein are used, but in children and small women the superficial femoral artery and the long saphenous vein are more suitable. On the day of perfusion the patient’s clinical, hamatological, and biochemical state is fully assessed. Previous conservative treatment is continued, and every attempt is made to correct any anaemia, hypoglycxmia, hypovolxmia, and electrolyte and acid-base imbalance. Just before perfusion blood-samples are taken for culture and for subsequent immunological studies. During perfusion the pulse, blood-pressure, central venous pressure, electrocardiogram, temperature, blood pH, bloodsugar, and plasma-electrolytes are monitored frequently. Preparation of the Animal 24-36 hours before perfusion two pigs (40-70 lb. [18-30 kg.] according to the size of the patient) are isolated and fed on a light diet with sugar-water and vitamin-E supplements. Intramuscular ampicillin is given. Just before use, one animal is hosed down and scrubbed, the other being kept as a standby. Preparation of the Liver Details of anxsthesia and hepatectomy have been given elsewhere,l5 and only important points will be mentioned here. Throughout hepatectomy extreme care is taken in handling the liver and the bowel. The animal is given intravenous dextran 40 injection (’ Rheomacrodex’) in dextrose, bicarbonate, and heparin to maintain an adequate bloodpressure, to ensure good hepatic perfusion, to maintain liver glycogen stores, and to counteract any metabolic acidosis. The liver is removed, and the portal vein and hepatic artery are rapidly cannulated with Redding’ left-atrial cannulx. The organ is then cooled and washed free of its blood with 8 litres of specially prepared balanced electrolyte solutionat 15°C. The suprahepatic vena cava and the common bileduct are cannulated, and a temperature probe is placed in the infrahepatic vena cava. The cooled asanguineous liver, with all its cannulx clamped, is transported to the perfusion apparatus which has already been assembled at the patient’s side in the ’
perfusion room. The Liver-perfusion Chamber We have found that prolonged liver perfusion is most successful when the physical environment of the extracorporeal liver is similar to that in the living animal. The liver chamber which we use was designed to simulate as closely as possible the normal physiological conditions. The chamber consists of three components: the outer container, the liver diaphragm, and the lid. The outer container is a stainless-steel cylinder, 10 in. (25 cm.) in diameter and 6 in. (15 cm.) high (fig. 1). Round its open top is welded a flange 2 in. (5 cm.) wide and 1 in. (2-5 cm.) high, which has eight equally spaced slots to receive corresponding studs from the metal ring of the liver diaphragm. On one side of the 7. Abouna, G. M., Ashcroft, T., Dale, G., Hull, C., Kirkley, J., Walder, D. N. Br. J. Surg. 1968, 55, 388. 8. Abouna, G. M. ibid. p. 761. 9. Abouna, G. M., Ashcroft, T., Muckle, J. T., Hull, C., Skillen. A., Kirkley, J. Br. J. Surg. 1968, 55, 862. G. M., Kirkley, J., Hull, C., Walder, D. N. Lancet, Aug. 31, 1968, p. 509.
10. Abouna,