1364
Preliminary report: Extracorporeal lung support for neonatal acute respiratory failure
A
technique for ventilatory support of lifethreatening neonatal acute respiratory failure by use of apnoeic oxygenation and low-frequency positive-pressure ventilation, with extracorporeal membrane CO2 removal through a single-cannula perfusion circuit, is described. 20 severely ill babies with respiratory failure were treated with this technique, 17 of whom survived with no clinical evidence of pulmonary handicap or neurological deficit at discharge from hospital. All 10 patients followed up at 6 months showed normal growth and development. Introduction A decade ago Gattinoni et all described the use in adults of a novel technique for respiratory support in which apnoeic oxygenation was achieved by low-frequency positivepressure ventilation of the lungs with an extracorporeal
membrane circuit to extract CO2, Such apnoeic oxygenation should avoid pulmonary barotrauma caused by the high pressures generated during conventional mechanical ventilation? We describe preliminary results of an investigation into the efficacy of this technique in newborn babies, in whom the risk of pulmonary barotrauma is greater than that in adults.
Patients and methods From May, 1987, to November, 1989, we treated 20 newborn babies with acute respiratory failure unresponsive to conventional treatments. Gestational age was 37-9 (SD 1-9) weeks; age at which extracorporeal lung support started was 38-1 (23-3) h; weight was 3-14 (069) kg; PP2 was 40 (14) mm Hg; and alveolar-arterial oxygen gradient (AaD02) was 638 (17) mm Hg. We began our clinical study of extracorporeal lung support in moribund patients, then based entry criteria on data published by Bartlett et aP and retrospective analysis of our own experience in the treatment of neonatal respiratory failure. The criteria used were: gestational age over 35 weeks, weight above 2 kg, no evidence of intracranial haemorrhage on cranial ultrasound examination, absence of major congenital malformation on clinical evaluation, exclusion of a congenital cardiac lesion as the cause of hypoxia, and no more than 7 days of aggressive assisted ventilation. A patient was considered for extracorporeal lung support when pulmonary failure was associated with acute deterioration, P a02 was below 40 mm Hg for 3 h or below 60 mm Hg for 12 h despite maximum ventilatory and pharmacological support (ie, sedated with fentanyl, paralysed with curare, ventilated with pure oxygen, peak airway pressure above 35 cm HO with a pressure-limited ventilator, mean airway pressure above 15 cm HO, inotropic support, and pulmonary vasodilatation). Some patients had been referred from other hospitals for extracorporeal lung support as a last therapeutic option. The underlying diagnosis of patients treated was meconium aspiration syndrome in 5, persistent pulmonary hypertension of the newborn in 7, sepsis in 5, respiratory distress syndrome in 2, and congenital diaphragmatic hernia in 1.
Fig 1-Perfusion circuit. A=single cannula, B=alternating clamp, C=pump, D=membrane lung, E= heat exchanger, F= liquid heater, G=doppler flowmeter 6 newborn babies were treated with a venovenous jugulofemoral perfusion circuit and the last 14 patients with a single-cannula circuit, which consisted of: a 7 or 8 French catheter (Jostra, Hechingen, West Germany), a pressure-time controlled alternating clamp (Gambro, Colombes, France), a non-occlusive roller pump (Collin-Cardio, Arcueil, France), a 0-8 m2 membrane lung (SciMed Life Systems, Minneapolis, Minnesota, USA), a heat exchanger (Dideco-Shyley, Irvine, California, USA), a liquid heater (Granulab, Illfurth, France), and a doppler flowmeter (Medicorp, Nancy, France) (fig 1). Tidal flow is generated by the alternating clamp and by a roller pump which turns at a constant rotor speed without interposition of a venous bladder. The silicon tubing of the rotor is collapsible and acts as a venous reservoir: thus blood pools in the tubing during the drainage phase and is reinjected during the infusion phase (fig 2). Pressure variations "downstream" from the pump activate the alternating clamp. Pressure rises during drainage and decreases during infusion; the activating pressures are preselected to obtain a 6 s total cycle with a drainage:infusion duration ratio of 2:1. The perfusion circuit was primed with 300 ml fresh citrated blood that contained 300 units heparin and 0-5 g calcium chloride. If spontaneous whole-blood activated clotting time exceeded 150 s before cannulation, heparin injection was delayed; otherwise the patient was given 25 units/kg heparin bolus as a priming dose. The right internal jugular vein was exposed by surgical cutdown and the single cannula introduced by the Seldinger technique and passed into the right atrium, where its position was confirmed by radiography. Perfusion circuit flow was started at 10% and gradually increased to 30-40% of cardiac output (assuming a normal cardiac index of 3 1/min per m2 body surface area [BSA]). Bloodflow and membrane ventilation were selected to obtain an arterial carbon-dioxide tension of 30-35 mm Hg. Once extracorporeal flow stabilised apnoeic oxygenation and lowfrequency positive-pressure ventilation were started. Apnoeic oxygenation was performed through the motionless natural lungs with a tracheal catheter positioned at the level of the carina. Oxygen was continuously infused at a flow rate of 1-21/min per m2 BSA. The lungs were inflated to obtain a positive continuous airway pressure of 8-14 cm H2O to prevent the resting lungs from alveolar collapse and to improve ventilation/perfusion relations, and respiratory rate was reduced to 4-6 cycles/min with a maximum pressure of 35
cm
H2O.
ADDRESSES: Paediatric Intensive Care Unit, Hôpital Trousseau, Paris (J.-Y. Chevalier, MD, J.-C Mathe, MD, Prof J. Costil, MD); and Department of Cardiac Surgery, Centre Medicochirurgical de la Porte de Choisy, Paris, France (Y Durandy, MD, A Batisse, MD). Correspondence to Dr J -Y. Chevalier, Réanimation Pédiatrique, Hôpital Trousseau, F-75571 Paris Cedex 12, France
1365
(7) cm H20. Mean (SD) PaC02 during extracorporeal lung support was 30-5 (5) mm Hg and ventilatory rate was 4-8 (09) per min. Extracorporeal bloodflow was 35 % (9) of total theoretical cardiac output and gas flow was 12 (02) 1/min. The complications of the procedure that occurred were bleeding, oliguric renal failure, and weight gain. Haemorrhage at the cannulation site occurred in 3 of our first 6 patients, who were treated with a jugulofemoral double circuit which required correction of the whole-blood activated clotting time to 250-300 s. Since use of the single-cannula circuit and a whole-blood activated clotting time of 150-180 s, local haemorrhage was only seen in 2 of 14 patients. 1 19 (SD 0-72) units of platelets were needed to maintain a platelet count above 50 000/ml. Oliguric prerenal failure occurred in 9 patients, but serum creatinine returned to normal within 25 (SD 07) days. Fluid overload was constant, but weights before the procedure were regained 59 (2-28) days after weaning off the perfusion circuit. The 17 survivors were discharged from hospital; the mean (SD) duration of their hospital stay was 37 5 (25-7) days, and none required supplementary oxygen after discharge. Neurological examination at discharge did not detect any sign of deficit, and at 6 months follow-up of 10 survivors indicated normal growth and development. 3 patients died-2 during extracorporeal lung support and 1 four days after its discontinuation.
Discussion Fig 2-Alternating clamp cycle. I=infusion line, D=drainage line, C=closed, O=open. 2: drainage line open, infusion line closed; pressure rises 1 & downstream from the pump and blood pools in tubing until clamp is activated 3 & 4: drainage line closed, infusion line open; pressure decreases downstream from the pump and blood is injected until clamp is activated.
During use of the extracorporeal lung support continuous, heparin infusion (about 25 units/kg per h) is necessary to prevent blood clotting in the circuit. Thrombocytopenia-a common result of extracorporeal membrane lung circuits-was treated with platelet transfusions when the platelet count fell below 50 000/ml. and cranial Daily electroencephalography ultrasonography were done to detect cerebral dysrhythmia or intracranial haemorrhage. Pulse oximetry and transcutaneous arterial oxygen and carbon-dioxide partial pressures were continuously monitored. Arterial blood gases were measured 4 to 6 times daily. Arterial PaOz was maintained between 70 and 100 mm Hg by lowering FIO2, first on the ventilator, then on the tracheal catheter, and lastly on the membrane. At an FIOz of 40% extracorporeal bloodflow was progressively decreased and low-dose
mechanical ventilation resumed. Patients were weaned from the perfusion circuit when Pa02 exceeded 70 mm Hg with an FIOz below 40 % on the ventilator, tracheal catheter, and membrane lung, and PaC02 was less than 35 mm Hg with an extracorporeal flow below 20% of the theoretical cardiac output.
Results 17 of 20 newborn babies (85%) were successfully treated by and weaned off extracorporeal lung support. Mean duration of such support was 96.h (SD 65 4; range 17-312) and mean (SD) duration of subsequent mechanical ventilation was 8 6 (63) days. After 3 h ofextrapulrnonary lung support mean (SD) Pa02 was 157 (48) mm Hg, allowing reduction of FIOz. Mean (SD) tracheal oxygen flow was 1 9 (0-6) 1/min per m2 BSA (ie, 04 [SD 0-1] 1/min), mean airway pressure was 11 (2) cm H2O, and peak inspiratory pressure was 35
All 20 newborn babies in our study had severe acute respiratory failure and were considered unlikely to survive with conventional treatments. Analysis of the efficacy of extracorporeal lung support is difficult because the target population is severely ill (sometimes too ill for all data to be obtained or analysed before treatment is started or rejected), double-blind crossover trials are impracticable, and there is no single, accurate predictor of outcome. However, there is some evidence that apnoeic oxygenation and low-frequency positive-pressure ventilation may improve gas exchange in the lungs. Compared with conventional mechanical ventilation, extracorporeal lung support is thought to enlarge alveolar recruitment at a lower mean airway pressure.4 In our experience there is an immediate and prolonged increase in Pa02 after the start of extracorporeal lung support, and a continuous positive airway pressure of 8-14 cm Hz0 seems to be an important factor in PaO2 improvement. In most patients, improved oxygenation is associated with resolution of chest radiographic changes: "white" lungs may be cleared and well aerated within 12-24 h, in accordance with studies in premature lambs.S The improved oxygenation depends on two factors: oxygen supplied by the natural lungs and oxygen supplied extracorporeally by the membrane lung. Arterial oxygenation due to the perfusion circuit is hard to quantify, especially if the membrane-oxygenated blood is diverted through a right-to-left atrial or ductal shunt. However, as it leaves the membrane blood should be fully saturated with oxygen; thus the maximum contribution of the membrane
whole-body oxygenation is approximately equivalent to the fraction of cardiac output that it receives.’ Similarly, carbon dioxide elimination should be achieved easily when 30-40% of total cardiac output passes through the extracorporeal circuit. A technique which needs a low extracorporeal flow is appropriate for a single-cannula tidal-flow circuit, and we have shown in dogs that carbon to
1366
dioxide elimination with a single-cannula tidal-flow circuit is equivalent to that obtained with a double-cannula continuous flow,6 because the low dead space of a single cannula and the 6 s total cycle duration (both drainage and infusion phases) minimise recirculation. COz removal was satisfactory in all our patients, with a mean PaCOz of 30-5 (SD 5) mm Hg. We did not measure natural lung carbon dioxide elimination, but with the low-frequency positivepressure ventilation (ie, low tidal volume at 48 [SD 0-9] cycles per min) this route is most unlikely to be an important factor in COz removal. In animals we have also found little effect on systemic haerrpdynamics by the tidal flow, and that large variations of righiheart preload do not modify mean systemic arterial pressure.6 In the patients, single-cannula perfusion was always well tolerated, with no haemodynamic
instability. Complications included haemorrhage, renal failure, and fluid overload. Bleeding at the cannula site seemed largely to depend on systemic heparinisation and thrombocytopenia; since use of the single cannula and reduced systemic heparinisation to obtain an activated clotting time of 150-180 s, bleeding has been rare and life-threatening haemorrhage has not occurred. Acute renal failure and fluid overload are common complications but transient and usually self-limiting; 2 patients required continuous haemofiltration, which was successful. 3 patients died. 1 had sudden cardiovascular collapse while on extracorporeal lung support; response had been encouraging and before the sudden deterioration he had nearly normal gas exchange with a PaO2 of above 370 mm Hg on pure oxygen. Necropsy showed no evidence of occult bleeding and no clear cause of death. In the other 2 patients extrapulmonary lung support was started late. 1 had congenital diaphragmatic hernia and cardiac arrest by the time of cannulation: 40 h later gas exchange had improved (PaO2 83 mm Hg at FIOz 40%; PaCOz 31 mm Hg) but electroencephalography was isoelectric and support was stopped. The other had persistent pulmonary hypertension with profound hypoxia and acidosis before cannulation. Extracorporeal lung support gave satisfactory gas exchange but the baby had striking neurological deficits after support was stopped, and died 4 days afterwards; further intervention was thought to be inappropriate. Thus in all 20 patients satisfactory gas exchanges were rapidly achieved during neonatal extracorporeal lung support, although 3 later died. The inclusion criteria and survival rate are similar to those reported by other centres.’ The technique may be of benefit to severely ill patients with respiratory failure, and may be especially useful in newborn babies. Further studies are needed to assess the effect on pulmonary arterial pressure of oxygenated blood directly injected into the pulmonary artery, to study cerebral bloodflow, and to optimise ventilatory management. If hypoxia during acute neonatal respiratory failure is mainly due to an intrapulmonary shunt and an intracardiac shunt caused by raised pulmonary artery pressure,8 venovenous perfusion with oxygenated blood directly injected into the pulmonary artery may be an alternative to venoarterial support, and may be simpler and less time-consuming. REFERENCES 1. Gattinoni
L, Agostini A, Pesenti A, et al. Treatment of acute respiratory failure with low-frequency positive-pressure ventilation and extracorporeal removal of CO2. Lancet 1980; ii: 292-94. 2. Kolobow T, Moretti MP, Fumagali R, et al. Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation. Am Rev Respir Dis 1987; 135: 312-15.
R, Gazzaniga A, Toomasian J, Corwin A, RoloffD, Rucker R. Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure, 100 cases. Ann Surg 1986; 204: 236-45. 4. Dorrington KL, McRae KM, Gardaz JP, Dunnil MS, Sykes MK, Wilkinson AR. A randomised comparison of total extracorporeal CO2 removal with conventional mechanical ventilation in experimental hyaline membrane disease. Intens Care Med 1989; 15: 184-91. 5. Trento A, Griffith BP, Hardesty RL. Extracorporeal membrane oxygenation: experience at the University of Pittsburgh. Ann Thorac Surg 1986; 42: 56-59. 6. Durandy Y, Chevalier JY, Lecompte Y. Single cannula venovenous bypass for respiratory membrane lung support. J Thorac Cardiovasc Surg 1990; 99: 404-09. 7. Moront GM, Katz NM, Keszler M, et al. Extracorporeal membrane oxygenation for neonatal respiratory failure. J Thorac Cardiovasc Surg 3. Bartlett
1989; 97: 706-14. 8. Hannerman C, Yousefzadeh D, Choi JH, Bui K. Persistent pulmonary hypertension of the newborn. Clin Perinatol 1989; 16: 137-55.
Preliminary report: Accurate assays for anti-HIV in urine
Untreated urine specimens from 358 patients (344 attending genito-urinary medicine clinics, 14 haemophiliacs) and 353 blood donors were tested blind by a simple IgG-capture particle-adherence test (GACPAT) and a rapid IgG-capture enzyme linked immunosorbent assay (GACELISA) for antibody to human immunodeficiency virus (antiHIV). All 158 urine specimens from seropositive subjects were anti-HIV positive by GACPAT and 157 of them (99·4%) were positive by GACELISA. Tests on 553 urine specimens from seronegative subjects gave two repeatable false-positive reactions by GACPAT (0·4%) and none by GACELISA. By means of a modified procedure anti-gp160 was detected by commercial western blot in the urine of 44 of 45 seropositive subjects examined. IgG-capture assays will detect anti-HIV in unconcentrated urine and so allow a diagnosis in when blood circumstances sampling is
impracticable. Introduction It is often inconvenient to collect blood for serological tests. colleagues described the detection of antibody to
Cao and
ADDRESSES: PHLS Virus Reference Laboratory, London (J. A. Connell, BSc, J. V. Parry, PhD, P. P. Mortimer, MD); Wellcome Diagnostics, Beckenham, Kent (R. J. S Duncan, PhD); Department of Genito-Urinary Medicine, West London Hospital (K. A. McLean, MRCP); Department of Genito-Urinary Medicine, University College and Middlesex School of Medicine, London (A. M. Johnson, MFCM); Public Health Laboratory, Leeds (M. H. Hambling, MD); North London Blood Transfusion Centre (J. Barbara, PhD); and PHLS Communicable Disease Surveillance Centre, London, UK (C P Farrington, PhD) Correspondence to Dr J. V. Parry, PHLS Virus Reference Laboratory, Colindale Avenue, London NW9 5HT, UK.
Preliminary report: Extracorporeal lung support for neonatal acute respiratory failure
A
technique for ventilatory support of lifethreatening neonatal acute respiratory failure by use of apnoeic oxygenation and low-frequency positive-pressure ventilation, with extracorporeal membrane CO2 removal through a single-cannula perfusion circuit, is described. 20 severely ill babies with respiratory failure were treated with this technique, 17 of whom survived with no clinical evidence of pulmonary handicap or neurological deficit at discharge from hospital. All 10 patients followed up at 6 months showed normal growth and development. Introduction A decade ago Gattinoni et all described the use in adults of a novel technique for respiratory support in which apnoeic oxygenation was achieved by low-frequency positivepressure ventilation of the lungs with an extracorporeal
membrane circuit to extract CO2, Such apnoeic oxygenation should avoid pulmonary barotrauma caused by the high pressures generated during conventional mechanical ventilation? We describe preliminary results of an investigation into the efficacy of this technique in newborn babies, in whom the risk of pulmonary barotrauma is greater than that in adults.
Patients and methods From May, 1987, to November, 1989, we treated 20 newborn babies with acute respiratory failure unresponsive to conventional treatments. Gestational age was 37-9 (SD 1-9) weeks; age at which extracorporeal lung support started was 38-1 (23-3) h; weight was 3-14 (069) kg; PP2 was 40 (14) mm Hg; and alveolar-arterial oxygen gradient (AaD02) was 638 (17) mm Hg. We began our clinical study of extracorporeal lung support in moribund patients, then based entry criteria on data published by Bartlett et aP and retrospective analysis of our own experience in the treatment of neonatal respiratory failure. The criteria used were: gestational age over 35 weeks, weight above 2 kg, no evidence of intracranial haemorrhage on cranial ultrasound examination, absence of major congenital malformation on clinical evaluation, exclusion of a congenital cardiac lesion as the cause of hypoxia, and no more than 7 days of aggressive assisted ventilation. A patient was considered for extracorporeal lung support when pulmonary failure was associated with acute deterioration, P a02 was below 40 mm Hg for 3 h or below 60 mm Hg for 12 h despite maximum ventilatory and pharmacological support (ie, sedated with fentanyl, paralysed with curare, ventilated with pure oxygen, peak airway pressure above 35 cm HO with a pressure-limited ventilator, mean airway pressure above 15 cm HO, inotropic support, and pulmonary vasodilatation). Some patients had been referred from other hospitals for extracorporeal lung support as a last therapeutic option. The underlying diagnosis of patients treated was meconium aspiration syndrome in 5, persistent pulmonary hypertension of the newborn in 7, sepsis in 5, respiratory distress syndrome in 2, and congenital diaphragmatic hernia in 1.
Fig 1-Perfusion circuit. A=single cannula, B=alternating clamp, C=pump, D=membrane lung, E= heat exchanger, F= liquid heater, G=doppler flowmeter 6 newborn babies were treated with a venovenous jugulofemoral perfusion circuit and the last 14 patients with a single-cannula circuit, which consisted of: a 7 or 8 French catheter (Jostra, Hechingen, West Germany), a pressure-time controlled alternating clamp (Gambro, Colombes, France), a non-occlusive roller pump (Collin-Cardio, Arcueil, France), a 0-8 m2 membrane lung (SciMed Life Systems, Minneapolis, Minnesota, USA), a heat exchanger (Dideco-Shyley, Irvine, California, USA), a liquid heater (Granulab, Illfurth, France), and a doppler flowmeter (Medicorp, Nancy, France) (fig 1). Tidal flow is generated by the alternating clamp and by a roller pump which turns at a constant rotor speed without interposition of a venous bladder. The silicon tubing of the rotor is collapsible and acts as a venous reservoir: thus blood pools in the tubing during the drainage phase and is reinjected during the infusion phase (fig 2). Pressure variations "downstream" from the pump activate the alternating clamp. Pressure rises during drainage and decreases during infusion; the activating pressures are preselected to obtain a 6 s total cycle with a drainage:infusion duration ratio of 2:1. The perfusion circuit was primed with 300 ml fresh citrated blood that contained 300 units heparin and 0-5 g calcium chloride. If spontaneous whole-blood activated clotting time exceeded 150 s before cannulation, heparin injection was delayed; otherwise the patient was given 25 units/kg heparin bolus as a priming dose. The right internal jugular vein was exposed by surgical cutdown and the single cannula introduced by the Seldinger technique and passed into the right atrium, where its position was confirmed by radiography. Perfusion circuit flow was started at 10% and gradually increased to 30-40% of cardiac output (assuming a normal cardiac index of 3 1/min per m2 body surface area [BSA]). Bloodflow and membrane ventilation were selected to obtain an arterial carbon-dioxide tension of 30-35 mm Hg. Once extracorporeal flow stabilised apnoeic oxygenation and lowfrequency positive-pressure ventilation were started. Apnoeic oxygenation was performed through the motionless natural lungs with a tracheal catheter positioned at the level of the carina. Oxygen was continuously infused at a flow rate of 1-21/min per m2 BSA. The lungs were inflated to obtain a positive continuous airway pressure of 8-14 cm H2O to prevent the resting lungs from alveolar collapse and to improve ventilation/perfusion relations, and respiratory rate was reduced to 4-6 cycles/min with a maximum pressure of 35
cm
H2O.
ADDRESSES: Paediatric Intensive Care Unit, Hôpital Trousseau, Paris (J.-Y. Chevalier, MD, J.-C Mathe, MD, Prof J. Costil, MD); and Department of Cardiac Surgery, Centre Medicochirurgical de la Porte de Choisy, Paris, France (Y Durandy, MD, A Batisse, MD). Correspondence to Dr J -Y. Chevalier, Réanimation Pédiatrique, Hôpital Trousseau, F-75571 Paris Cedex 12, France
1365
(7) cm H20. Mean (SD) PaC02 during extracorporeal lung support was 30-5 (5) mm Hg and ventilatory rate was 4-8 (09) per min. Extracorporeal bloodflow was 35 % (9) of total theoretical cardiac output and gas flow was 12 (02) 1/min. The complications of the procedure that occurred were bleeding, oliguric renal failure, and weight gain. Haemorrhage at the cannulation site occurred in 3 of our first 6 patients, who were treated with a jugulofemoral double circuit which required correction of the whole-blood activated clotting time to 250-300 s. Since use of the single-cannula circuit and a whole-blood activated clotting time of 150-180 s, local haemorrhage was only seen in 2 of 14 patients. 1 19 (SD 0-72) units of platelets were needed to maintain a platelet count above 50 000/ml. Oliguric prerenal failure occurred in 9 patients, but serum creatinine returned to normal within 25 (SD 07) days. Fluid overload was constant, but weights before the procedure were regained 59 (2-28) days after weaning off the perfusion circuit. The 17 survivors were discharged from hospital; the mean (SD) duration of their hospital stay was 37 5 (25-7) days, and none required supplementary oxygen after discharge. Neurological examination at discharge did not detect any sign of deficit, and at 6 months follow-up of 10 survivors indicated normal growth and development. 3 patients died-2 during extracorporeal lung support and 1 four days after its discontinuation.
Discussion Fig 2-Alternating clamp cycle. I=infusion line, D=drainage line, C=closed, O=open. 2: drainage line open, infusion line closed; pressure rises 1 & downstream from the pump and blood pools in tubing until clamp is activated 3 & 4: drainage line closed, infusion line open; pressure decreases downstream from the pump and blood is injected until clamp is activated.
During use of the extracorporeal lung support continuous, heparin infusion (about 25 units/kg per h) is necessary to prevent blood clotting in the circuit. Thrombocytopenia-a common result of extracorporeal membrane lung circuits-was treated with platelet transfusions when the platelet count fell below 50 000/ml. and cranial Daily electroencephalography ultrasonography were done to detect cerebral dysrhythmia or intracranial haemorrhage. Pulse oximetry and transcutaneous arterial oxygen and carbon-dioxide partial pressures were continuously monitored. Arterial blood gases were measured 4 to 6 times daily. Arterial PaOz was maintained between 70 and 100 mm Hg by lowering FIO2, first on the ventilator, then on the tracheal catheter, and lastly on the membrane. At an FIOz of 40% extracorporeal bloodflow was progressively decreased and low-dose
mechanical ventilation resumed. Patients were weaned from the perfusion circuit when Pa02 exceeded 70 mm Hg with an FIOz below 40 % on the ventilator, tracheal catheter, and membrane lung, and PaC02 was less than 35 mm Hg with an extracorporeal flow below 20% of the theoretical cardiac output.
Results 17 of 20 newborn babies (85%) were successfully treated by and weaned off extracorporeal lung support. Mean duration of such support was 96.h (SD 65 4; range 17-312) and mean (SD) duration of subsequent mechanical ventilation was 8 6 (63) days. After 3 h ofextrapulrnonary lung support mean (SD) Pa02 was 157 (48) mm Hg, allowing reduction of FIOz. Mean (SD) tracheal oxygen flow was 1 9 (0-6) 1/min per m2 BSA (ie, 04 [SD 0-1] 1/min), mean airway pressure was 11 (2) cm H2O, and peak inspiratory pressure was 35
All 20 newborn babies in our study had severe acute respiratory failure and were considered unlikely to survive with conventional treatments. Analysis of the efficacy of extracorporeal lung support is difficult because the target population is severely ill (sometimes too ill for all data to be obtained or analysed before treatment is started or rejected), double-blind crossover trials are impracticable, and there is no single, accurate predictor of outcome. However, there is some evidence that apnoeic oxygenation and low-frequency positive-pressure ventilation may improve gas exchange in the lungs. Compared with conventional mechanical ventilation, extracorporeal lung support is thought to enlarge alveolar recruitment at a lower mean airway pressure.4 In our experience there is an immediate and prolonged increase in Pa02 after the start of extracorporeal lung support, and a continuous positive airway pressure of 8-14 cm Hz0 seems to be an important factor in PaO2 improvement. In most patients, improved oxygenation is associated with resolution of chest radiographic changes: "white" lungs may be cleared and well aerated within 12-24 h, in accordance with studies in premature lambs.S The improved oxygenation depends on two factors: oxygen supplied by the natural lungs and oxygen supplied extracorporeally by the membrane lung. Arterial oxygenation due to the perfusion circuit is hard to quantify, especially if the membrane-oxygenated blood is diverted through a right-to-left atrial or ductal shunt. However, as it leaves the membrane blood should be fully saturated with oxygen; thus the maximum contribution of the membrane
whole-body oxygenation is approximately equivalent to the fraction of cardiac output that it receives.’ Similarly, carbon dioxide elimination should be achieved easily when 30-40% of total cardiac output passes through the extracorporeal circuit. A technique which needs a low extracorporeal flow is appropriate for a single-cannula tidal-flow circuit, and we have shown in dogs that carbon to
1366
dioxide elimination with a single-cannula tidal-flow circuit is equivalent to that obtained with a double-cannula continuous flow,6 because the low dead space of a single cannula and the 6 s total cycle duration (both drainage and infusion phases) minimise recirculation. COz removal was satisfactory in all our patients, with a mean PaCOz of 30-5 (SD 5) mm Hg. We did not measure natural lung carbon dioxide elimination, but with the low-frequency positivepressure ventilation (ie, low tidal volume at 48 [SD 0-9] cycles per min) this route is most unlikely to be an important factor in COz removal. In animals we have also found little effect on systemic haerrpdynamics by the tidal flow, and that large variations of righiheart preload do not modify mean systemic arterial pressure.6 In the patients, single-cannula perfusion was always well tolerated, with no haemodynamic
instability. Complications included haemorrhage, renal failure, and fluid overload. Bleeding at the cannula site seemed largely to depend on systemic heparinisation and thrombocytopenia; since use of the single cannula and reduced systemic heparinisation to obtain an activated clotting time of 150-180 s, bleeding has been rare and life-threatening haemorrhage has not occurred. Acute renal failure and fluid overload are common complications but transient and usually self-limiting; 2 patients required continuous haemofiltration, which was successful. 3 patients died. 1 had sudden cardiovascular collapse while on extracorporeal lung support; response had been encouraging and before the sudden deterioration he had nearly normal gas exchange with a PaO2 of above 370 mm Hg on pure oxygen. Necropsy showed no evidence of occult bleeding and no clear cause of death. In the other 2 patients extrapulmonary lung support was started late. 1 had congenital diaphragmatic hernia and cardiac arrest by the time of cannulation: 40 h later gas exchange had improved (PaO2 83 mm Hg at FIOz 40%; PaCOz 31 mm Hg) but electroencephalography was isoelectric and support was stopped. The other had persistent pulmonary hypertension with profound hypoxia and acidosis before cannulation. Extracorporeal lung support gave satisfactory gas exchange but the baby had striking neurological deficits after support was stopped, and died 4 days afterwards; further intervention was thought to be inappropriate. Thus in all 20 patients satisfactory gas exchanges were rapidly achieved during neonatal extracorporeal lung support, although 3 later died. The inclusion criteria and survival rate are similar to those reported by other centres.’ The technique may be of benefit to severely ill patients with respiratory failure, and may be especially useful in newborn babies. Further studies are needed to assess the effect on pulmonary arterial pressure of oxygenated blood directly injected into the pulmonary artery, to study cerebral bloodflow, and to optimise ventilatory management. If hypoxia during acute neonatal respiratory failure is mainly due to an intrapulmonary shunt and an intracardiac shunt caused by raised pulmonary artery pressure,8 venovenous perfusion with oxygenated blood directly injected into the pulmonary artery may be an alternative to venoarterial support, and may be simpler and less time-consuming. REFERENCES 1. Gattinoni
L, Agostini A, Pesenti A, et al. Treatment of acute respiratory failure with low-frequency positive-pressure ventilation and extracorporeal removal of CO2. Lancet 1980; ii: 292-94. 2. Kolobow T, Moretti MP, Fumagali R, et al. Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation. Am Rev Respir Dis 1987; 135: 312-15.
R, Gazzaniga A, Toomasian J, Corwin A, RoloffD, Rucker R. Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure, 100 cases. Ann Surg 1986; 204: 236-45. 4. Dorrington KL, McRae KM, Gardaz JP, Dunnil MS, Sykes MK, Wilkinson AR. A randomised comparison of total extracorporeal CO2 removal with conventional mechanical ventilation in experimental hyaline membrane disease. Intens Care Med 1989; 15: 184-91. 5. Trento A, Griffith BP, Hardesty RL. Extracorporeal membrane oxygenation: experience at the University of Pittsburgh. Ann Thorac Surg 1986; 42: 56-59. 6. Durandy Y, Chevalier JY, Lecompte Y. Single cannula venovenous bypass for respiratory membrane lung support. J Thorac Cardiovasc Surg 1990; 99: 404-09. 7. Moront GM, Katz NM, Keszler M, et al. Extracorporeal membrane oxygenation for neonatal respiratory failure. J Thorac Cardiovasc Surg 3. Bartlett
1989; 97: 706-14. 8. Hannerman C, Yousefzadeh D, Choi JH, Bui K. Persistent pulmonary hypertension of the newborn. Clin Perinatol 1989; 16: 137-55.
Preliminary report: Accurate assays for anti-HIV in urine
Untreated urine specimens from 358 patients (344 attending genito-urinary medicine clinics, 14 haemophiliacs) and 353 blood donors were tested blind by a simple IgG-capture particle-adherence test (GACPAT) and a rapid IgG-capture enzyme linked immunosorbent assay (GACELISA) for antibody to human immunodeficiency virus (antiHIV). All 158 urine specimens from seropositive subjects were anti-HIV positive by GACPAT and 157 of them (99·4%) were positive by GACELISA. Tests on 553 urine specimens from seronegative subjects gave two repeatable false-positive reactions by GACPAT (0·4%) and none by GACELISA. By means of a modified procedure anti-gp160 was detected by commercial western blot in the urine of 44 of 45 seropositive subjects examined. IgG-capture assays will detect anti-HIV in unconcentrated urine and so allow a diagnosis in when blood circumstances sampling is
impracticable. Introduction It is often inconvenient to collect blood for serological tests. colleagues described the detection of antibody to
Cao and
ADDRESSES: PHLS Virus Reference Laboratory, London (J. A. Connell, BSc, J. V. Parry, PhD, P. P. Mortimer, MD); Wellcome Diagnostics, Beckenham, Kent (R. J. S Duncan, PhD); Department of Genito-Urinary Medicine, West London Hospital (K. A. McLean, MRCP); Department of Genito-Urinary Medicine, University College and Middlesex School of Medicine, London (A. M. Johnson, MFCM); Public Health Laboratory, Leeds (M. H. Hambling, MD); North London Blood Transfusion Centre (J. Barbara, PhD); and PHLS Communicable Disease Surveillance Centre, London, UK (C P Farrington, PhD) Correspondence to Dr J. V. Parry, PHLS Virus Reference Laboratory, Colindale Avenue, London NW9 5HT, UK.
