ORIGINAL ARTICLES

Use of extracorporeal membrane oxygenation in the treatment of respiratory syncytial virus bronchiolitis: The national experience, '1983 to '1988 Robin H, Steinhorn, MD, a n d Thomas P. G r e e n , MD From the Department of Pediatrics, University of Minnesota, Minneapolis, and the Minnesota Regional ECMO Program, a cooperative effort of the Minneapolis Children's Medical Center and the Variety Club Children's Hospital at the University of Minnesota In an effort to obtain d a t a to provide the basis for the design of controlled clinical trials, we c o n t a c t e d all U.S. participants in the National ECMO Registry to assemble the national e x p e r i e n c e on the use of extracorporeal membrane oxy g e n a t i o n in respiratory syncytial virus bronchiolitis during the past 5 years. Twelve infants were treated at nine centers b e t w e e n 1983 and 1988. Eight had b e e n born prematurely, and five had b r o n c h o p u l m o n a r y dysplasia. The mean a g e at onset of infection with respiratory syncytial virus was 108 +_ 102 days. The mean length of ventilator m a n a g e m e n t before extracorporeal membrane oxy g e n a t i o n was 7.8 + 7.1 days. All infants had persistent h y p o x e m i a with a mean arterial o x y g e n pressure of 39.2 _+ 11.7 torr (5.3 _+ 1.6 kPa) despite high ventilator pressures (mean airway pressure 19.7 _+ 6.4 c m H2O) and 100% inspired oxygen; six had air leak syndrome. Seven infants survived (58%). The mean duration of extracorporeal m e m b r a n e o x y g e n a t i o n for survivors was 233 _+ 139 hours. Preexisting chronic lung disease did not predict a poor outcome: four of the five infants with bronchopulmonary dysplasia survived. Six of the survivors have subsequently a c h i e v e d e x p e c t e d d e v e l o p m e n t a l milestones and one has slight motor delay. We c o n c l u d e that, for infants with severe respiratory syncytial virus bronchiolitis whose condition deteriorates despite maximal ventilator management, extracorporeal membrane o x y g e n a t i o n may provide lifesaving support. The duration of successful treatment with this therapy may be longer than that for c o n v e n t i o n a l neonatal indications, but e x c e l l e n t neurologic o u t c o m e may be e x p e c t e d in survivors. (J PEDIATR1990;116:338-42)

Extracorporeal membrane oxygenation can provide complete but temporary respiratory support for patients with life-threatening pulmonary or pulmonary vascular disease. 15 As experience with this technique has accumulated, Submitted for publication June 23, 1989; accepted Aug, 30, 1989. Reprint requests: Robin H. Steinhorn, MD, Minnesota Regional ECMO Program, Box 104 UMHC, Harvard St. at East River Rd., Minneapolis, MN 55455. 9/20/16488

338

ECMO-related complications have decreased and patient survival rates have improved. 6 Appropriate patient selection for this costly and invasive technology remains problematic. Controlled clinical trials are needed to compare efficacy, risks, and cost of ECMO treatment with conventional medical management for each potential clinical application. Trials are currently under way for conditions such as meconium aspiration syndrome and congenital diaphragmatic hernia. Meanwhile, ECMO is being used widely on a compassionate basis when a treat-

Volume 116 Number 3

ECMO RSV

ECMO for bronchiolitis

Extracorporeal membrane oxygenation Respiratory syncytial virus

I

See commentary, p. 393.

able or self-limited condition produces life-threatening respiratory failure and all less costly and less invasive therapies have failed. After the successful rescue of a moribund infant with respiratory syncytial virus bronchiolitis with the use of E C M O , we contacted all U.S. participants in the National E C M O Registry to assemble the national.experience with E C M O in this disease. This experience should be useful to physicians who are treating patients with severe R S V infections, as well as to those who are developing criteria for controlled E C M O clinical trials.

339

One year after this illness, the patient has no oxygen requirement except during acute respiratory infections. A mild developmental delay, which is primarily motor, is present. Cognitive development appears appropriate.

METHODS The medical director or clinical coordinator at each of the 37 U.S. centers participating in the National E C M O Registry was contacted by telephone during March 1988 and asked to identify any infant with RSV bronchiolitis treated with E C M O at his or her center. Twelve patients were identified. The medical records were reviewed, and a data base form, developed for this study, was completed for those infants. All data are expressed as mean _+ SD unless otherwise indicated. Statistical analysis was performed with the Student t test. RESULTS

CASE REPORT A male infant, born at 25 or 26 weeks of gestational age, required 37 days of mechanical ventilation during the newborn period and 30 additional days of oxyge'n and diuretic therapy. He was discharged to his home at 3 months of age, requiring no medications. He was readmitted 2 weeks later for apnea and cyanosis. RSV antigen was detected in nasopharyngeal secretions by fluorescent antibody. Progressive respiratory failure ensued, necessitating mechanical ventilation. Despite the use of aerosolized ribavirin, respiratory function continued to deteriorate. On hospital day 12, bilateral pneumothorax developed and high-frequency jet ventilation was instituted. Pulmonary air leak continued to worsen, however, necessitating the placement of additional thoracostomy tubes. A high-volume, continuous air leak was present in all chest tubes. On hospital day 16, hourly episodes of hypotension responded only to manual evacuation of additional pleural air. A representative arterial blood sample during this time revealed the following: pH, 7.13 units; carbon dioxide pressure, 92 torr (12.3 kPa); and oxygen pressure, 60 torr (8.0 kPa). Attending physicians believed that the probability of survival with conventional medical management was remote. Accordingly, a trial of ECMO was elected. After explaining the risks and potential complications and obtaining consent from the family, we began venoarterial ECMO on hospital day 16. All positive airway pressure was discontinued for 48 hours to allow closure of the pulmonary air leak] Pulmonary compliance, chest radiography, and pulmonary carbon dioxide excretion during partial bypass periods were used to assess pulmonary improvement. However, no improvement was detected for 17 days. The patient showed dramatic improvement with no specific changes in therapy on day 18 of bypass, and the cannulas were removed 24 hours later. The endotracheal tube was removed after I0 further days of mechanical ventilation, and the infant was discharged to his home shortly thereafter.

Of the 37 participating centers, nine reported treating a total of 12 patients with RSV infection between 1983 and 1988 (Table). Nine patients were treated during 1987 and 1988.

Patient population Neonatal history. Eight patients (67%) had a gestational age of less than 34 weeks. Mean birth weight was 2290 _+ 1258 gin, with three patients having a birth weight of _< 1000 gm. Six patients required mechanical ventilation in the neonatal period. Bronchopulmonary dysplasia subsequently developed in five patients; four required treatment with oxygen and diuretics for 2 months or longer. Bronchiolitis. The mean age at onset of the symptoms of bronchiolitis was 108 _+ 102 days. All patients were seen between the months of October and the early part of March. The diagnosis of RSV infection was established by fluorescent antibody study in four patients, and enzyme-linked immunosorbent assay in six patients. In three patients the diagnosis was confirmed by antibody titers. P r e - E C M O therapy. All patients were treated with conventional mechanical ventilation before E C M O ; two patients additionally received trials of high-frequency ventilation. The mean ventilator rate was 69 _+ 62 breaths/rain; mean peak inspiratory pressure was 38.6 + 7.3 cm H 2 0 and mean end-expiratory pressure was 7.5 _+ 4.6 cm H20; and mean airway pressure was 19.7 +_ 6.4 cm H 2 0 . All patients were treated with inspired oxygen concentrations of 100%. Nine patients were treated with aerosolized ribavirin. The mean duration of treatment with mechanical ventilation before E C M O was 7.8 -+ 7.1 days. Arterial blood gas values before E C M O were as follows:

34 0

Steinhorn and Green

The JournalofPediatrics March 1990

Table. Patient characteristics

Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 All patients Mean or % SD Survivors Mean or % SD Nonsurvivors Mean or% SD

Gestational age (wk)

BPD

Onset RSV (days)

Ventilation pre-ECMO (days)

ECMO duration (hr)

Survival

33 28 40 33 33 32 40 40 29 26 28 40

+ + + + + -

30 138 19 27 79 242 63 72 161 117 348 7

8 5 1 8 27 7 1 8 5 10 7 2

233 165 125 308 288 432 98 360 186 428 360 200

+ + + + + + +

34 5

42%

109 102

8 7

265 114

58%

34 6

57%

107 84

5 3

233 139

100%

33 4

20%

111 134

12 9

310 53

0%

BPD. Bronchopulmonary dysplasia.

mean pH, 7.38 _+ 0.2 units; mean arterial carbon dioxide pressure, 43 _+ 18 torr (5.7 +_ 2.4 kPa); and mean arterial oxygen pressure, 39.2 _+ 11.7 torr (5.3 _+ i.6 kPa). Other calculated indexes of impaired gas exchange showed a mean alveolar-arterial oxygen difference of 639 _+ 18.8 and a mean oxygenation index, 3 calculated with the use of mean airway pressure, forced inspiratory oxygen, and arterial oxygen pressure, of 47.6 _+ 18.5. In addition, seven patients had air leaks, with five requiring chest tubes for pneumothorax. Two patients had a cardiac arrest before initiation of ECMO. E C M O c o u r s e and o u t c o m e . All patients were treated with venoarterial E C M O . The mean duration of E C M O support in survivors was 233 +_ 139 hours. Two patients (Nos. 6 and 10) required support for 462 and 428 hours, respectively. Seven of twelve patients survived. Four of the surviving infants had preexisting bronchopulmonary dysplasia. The mean duration of ventilator therapy before E C M O among survivors was 5.5 _+ 4.8 days. Three of the patients with pneumothorax before E C M O survived. Follow-up examinations showed that five patients were normal. One patient had slight muscle weakness, although, on the whole, development was thought to be within normal limits. One patient with congenital myotonic dystrophy has significant developmental delay but has achieved expected

milestones. Four patients had residual lung disease at the time of discharge, with two requiring home oxygen therapy. All patients have had pulmonary improvement, and none currently requires supplemental oxygen. Five patients died. The mean duration of ventilator therapy before E C M O in this group was 12.2 _+ 8.3 days. Each had E C M O electively terminated after approximately 2 weeks of therapy. Four patients died of respiratory failure, with lung biopsy specimens in two showing diffuse interstitial fibrosis; one death was caused by overwhelming sepsis. The mean duration of E C M O support for nonsurvivors was 310 _ 53 hours. DISCUSSION Although E C M O appears to be a lifesaving method of support for specific respiratory illnesses in newborn infants, indications for this therapy in children outside this age group are undefined. Our report demonstrates a potential use of E C M O in the pediatric age group: the treatment of life-threatening respiratory infection with RSV. Infection with RSV is a major cause of hospitalization of children with respiratory infections, 8 and the overall mortality rate is approximately 5/10,000 cases. 9 Hospitalized patients have a mortality rate of 2% to 5%. l~ Infants born prematurely are more likely to require hospitalization dur-

Volume 116 Number 3

ing an R S V infection, especially if their history includes mechanical ventilation in the newborn period and subsequent bronchopulmonary dysplasia. 1~ Infants with congenital heart disease, ~1,13 other congenital anomalies, tl pulmonary hypertension, 13 or compromised immune function 14 account for much of the overall mortality rate from RSV infection, although death from an RSV infection in a previously normal patient has been reported. 15 Specific guidelines for the use of E C M O in the treatment of RSV bronchiolitis cannot be generalized from the small, uncontrolled experience reported here. Only prospective, randomized studies will be able to delineate the utility of E C M O for respiratory failure in the pediatric age g r o u p . However, several aspects of this early experience may prove useful for future patient selection and for the appropriate design of controlled clinical trials. First, 58% of these patients survived with the use of E C M O . Each patient was thought to have little or no chance of survival if conventional medical therapy were continued. All received maximal ventilatory support according to the standards of their individual institution, or their condition had deteriorated to the point of severe acidosis or cardiac arrest at the time of E C M O initiation. Nonetheless, it is not possible to determine whether E C M O improved the survival rate for these patients. Second, the preceding diagnosis of bronchopulmonary dysplasia did not predict a worse outcome with E C M O : four of the five infants with chronic lung disease survived. However, surviving patients had a shorter p r e - E C M O ventilator course (5.5 _+ 4.8 days) than nonsurviving patients (11,8 _+8.5 days); only one of five patients with a ventilator course of more than 7 days during the acute RSV illness survived. Third, the duration of E C M O in the group of survivors (mean 233 hours) was longer than the average duration of E C M O for conventional neonatal indications (118 hours).2, 6 Two surviving patients had extremely prolonged E C M O support (more than 2 weeks). Each had no significant improvement in oxygenation until extremely late into the E C M O course of therapy. Fourth, a favorable neurologic outcome was seen in survivors. One of the most worrisome aspects of venoarterial E C M O is the necessity of ligating the right common carotid artery. Although the consequences of carotid ligations may not become apparent for many years, the short-term results in our patients and the longer follow-up periods in several newborn studies 16~8 are encouraging. Finally, no deaths in this series were directly related to E C M O . This therapy was electively terminated in four cases after the pulmonary disease failed to improve and in

E C M O f o r bronchiolitis

341

one case because of sepsis. The mean duration of E C M O in this group of patients of slightly more than 12 days perhaps reflects the belief that 2 weeks is a reasonable period for recovery from an acute pulmonary insult. The observation that two surviving patients required therapy for 19 and 21 days, respectively, may signify that complete recovery can require more than 2 weeks. Further controlled clinical trials are needed to define the role of E C M O in the treatment of respiratory failure in infants and children. The experience reported here may be useful in developing patient selection criteria, treatment protocols, and outcome expectations. We are indebted to the following persons who contributed their time and effort to obtain the patient data summarized in this report: Michael Klein, MD, Children's Hospital of Michigan, Detroit; Larry Cook, MD, University of Louisville, Louisville, Ky.; Cindy Stephens and Thomas Weber, MD, Cardinal Glennon Hospital, St. Louis, Mo.; Robert Arensman, MD, Ochsner Clinic, New Orleans, La.; Ernesto Gangitano, MD, Huntington Memorial Hospital, Pasadena, Calif.; Jan Carter, MD, Wilford Hall USAF Medical Center, San Antonio, Tex.; and Donald W. Thibeault, MD, Children's Mercy Hospital, Kansas City, Mo. We also acknowledge the ongoing commitment by the University of Michigan ECMO Program (Sandy Snedecor, Robin Chapman, and Robert Bartlett) to maintaining the National ECMO Registry. The Registry made this report possible. REFERENCES

1. Bartlett RH, Roloff DW, Cornell RG, Andrews AF, Dillon PW, Zwischenberger JB. Extracorporeal circulation in neonatal respiratory failure: a prospective randomized study. Pediatrics 1985;76:479-87. 2. Toomasian JM, Snedecor SM, Cornell RG, Cilley RE, Bartlett RH. Neonatal experience with extracorporeaI membrane oxygenation in newborn respiratory failure: data from 715 cases. Trans Am Soc Artif Intern Organs 1988;34:140-7. 3. Ortiz RM, Cilley RE, Bartlett RH. Extracorporeal membrane oxygenation in pediatric respiratory failure. Pediatr Clin North Am 1987;34:39-46. 4. Short BL, Pearson GD. Neonatal extracorporeal membrane oxygenation: a review. Intensive Care Med 1986;1:47-54. 5. Kanter KR, Pennington DG, Weber T R, Zambie MA, Braun P, Martyehenko V. Extracorporeal membrane oxygenation for postoperative cardiac support in children. J Thorac Cardiovasc Surg 1987;93:27-35. 6. Bartlett RH, Chapman RA, Snedecor S. Neonatal ECMO Registry Report, National Summary, University of Michigan, Ann Arbor, January 1989. 7. Frattalone JM, Fuhrman BP, Kochanek PM, et al. Management of pulmonary barotrauma by extracorporeal membrane oxygenation, apnea and lung rest. J PEDIATR1988;112:787-9. 8. Report to the Medical Research Council Subcommittee on Respiratory Syneytial Virus Vaccines. Respiratory syncytial virus infection: admission to hospital in industrial, urban and rural areas. Br Med J 1978;2:796-8.

342

S t e i n h o r n and Green

The Journal o f Pediatrics March 1990

9. Henderson FW, Collier A, Clyde WA, Denny FW. Respiratory syncytial virus infections, reinfection, and immunity: a prospective longitudinal study in young children. N Engl J Med 1979;300:530-4. 10. Rodriguez W J, Parrott RH. Ribavirin aerosol treatment of serious respiratory syncytial virus infection in infants. Infect Dis Clin North Am 1987;1:425-39. 11. Krasinski K. Severe respiratory syncytial virus infection: clinical features, nosocomial acquisition and outcome. Pediatr Infect Dis 1985;4:250-7. 12. Frankel LR, Lewiston N J, Smith DW, Stevenson DK. Clinical observations on mechanical ventilation for respiratory failure in bronchiolitis. Pediatr Pulmonol 1986;2:307-11. t 3. MacDonald NE, Hall CB, Suffin SC, Alexson C, Harris P J, Manning JA. Respiratory syncytial viral infection in infants with congenital heart disease. N Engl J Med 1982;307:397400.

14. Hall CB, Powell KR, MacDonald NE, et al. Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med 1986;315:77-81. 15. Kurlandsky LE, French G, Webb PM, Porter DD. Fatal respiratory syncytial virus pneumonitis in a previously healthy child. Am Rev Respir Dis 1988;I 38:468-72. 16. Andrews AF, Nixon CA, Roloff DW, et al. One- to three-year outcome of fourteen neonatal ECMO survivors. Pediatrics 1986;78:692-8. 17. Towne BH, Lott IT, Hicks DA, Healey T. Long-term followup of infants and children treated with extracorporeal membrane oxygenation (ECMO): a preliminary report. J Pediatr Surg 1984;20:410-4. 18. Krummel TM, Greenfield L J, Kirkpatrick BV, et al. The early evaluation of survivors after extracorporeal membrane oxegenation for neonatal pulmonary failure. J Pediatr Surg 1984; 19:585-90.

FELLOWSHIPS Available fellowships in pediatric subspecialties and those for general academic pediatric training are listed once a year, in May, in THE JOURNAL OF PEDIATRICS. Each October, forms for listing such fellowships are sent to the Chairman of the Department of Pediatrics at most major hospitals in the United States and Canada. Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to The C.V. Mosby Company by February 15 of the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, The C.V. Mosby Company, 11830 Westline Industrial Drive, St. Louis, M O 63146-3318/314-872-8370.

Use of extracorporeal membrane oxygenation in the treatment of respiratory syncytial virus bronchiolitis: the national experience, 1983 to 1988.

In an effort to obtain data to provide the basis for the design of controlled clinical trials, we contacted all U.S. participants in the National ECMO...
388KB Sizes 0 Downloads 0 Views