Ronald B. Hirschl

Extracorporeal Life Support for Severe Acute Respiratory Distress Syndrome in Adults

Objective:Severe acute respiratory distress syndrome (ARDS) is associated with a high level of mortality. Extracorporeal life support (ECLS) during severe ARDS maintains oxygen and carbon dioxide gas exchange while providing an optimal environment for recovery of pulmonary function. Since 1989, we have used a protocol-driven algorithm for treatment of severe ARDS, which includes the use of ECLS when standard therapy fails. The objective of this study was to evaluate our experience with ECLS in adult patients with severe ARDS with respect to mortality and morbidity. Methods:We reviewed our complete experience with ELCS in adults from January 1, 1989, through December 31, 2003. Severe ARDS was defined as acute onset pulmonary failure, with bilateral infiltrates on chest x-ray, and PaO2/fraction of inspired oxygen (FiO2) ratio ≤100 or A-aDO2 >600 mm Hg despite maximal ventilator settings. The indication for ECLS was acute severe ARDS unresponsive to optimal conventional treatment. The technique of ECLS included veno-venous or veno-arterial vascular access, lung “rest” at low FiO2 and inspiratory pressure, minimal anticoagulation, and optimization of systemic oxygen delivery. Results:During the study period, ECLS was used for 405 adult patients age 17 or older. Of these 405 patients, 255 were placed on ECLS for severe ARDS refractory to all other treatment. Sixty-seven percent were weaned off ECLS, and 52% survived to hospital discharge. Multivariate logistic regression analysis identified the following pre-ELCS variables as significant independent predictors of survival: (1) age (P = 0.01); (2) gender (P = 0.048); (3) pH ≤7.10 (P = 0.01); (4) PaO2/FiO2 ratio (P = 0.03); and (5) days of mechanical ventilation (P < 0.001). None of the patients who survived required permanent mechanical ventilation or supplemental oxygen therapy. Conclusion:Extracorporeal life support for severe ARDS in adults is a successful therapeutic option in those patients who do not respond to conventional mechanical ventilator strategies.

Current surgical management of congenital diaphragmatic hernia: A report from the congenital diaphragmatic hernia study group

BACKGROUND Repair of congenital diaphragmatic hernia (CDH) has changed from an emergent procedure to a delayed procedure in the last decade. Many other aspects of management have also evolved since the first successful repair. However, most reports are from single institutions. The lack of a large multicenter database has hampered progress in the management of congenital diaphragmatic hernia (CDH) and makes determination of the current standard difficult. METHODS The CDH study group was formed in 1995 to collect data from multiple institutions in North America, Europe, and Australia. Participating centers completed a registry form on all live-born infants with CDH during 1995 and 1996. Demographic information, data about surgical management, and outcome were collected for all patients. RESULTS Sixty-two centers participated, with 461 patients entered. Overall survival was 280 of 442 patients (63%) where survival was recorded. The defect was left-sided in 78%, right-sided in 21%, and bilateral in 1%. A subcostal approach was used in 91% of patients, with pleural drainage used in 76%. A patch of some kind was used in just over half (51%) of the patients, with polytetrafluoroethylene being the most commonly used material (81%) in those patients with a patch. The mean surgical time was 102 minutes, with an average blood loss of 14 mL (range, 0 to 500 mL). The overwhelming majority of patients underwent repair between 6:00 AM and 6:00 PM (289 of 329, 88%). Nineteen percent of patients had surgical repair on extracorporeal membrane oxygenation (ECMO) at a mean time of 170 hours into the ECMO course (range, 10 to 593 hours). The mean age at surgery in patients not treated with ECMO was 73 hours (range, 1 to 445 hours). CONCLUSIONS The multicenter nature of this report makes it a snapshot of current management. The data would indicate that prosthetic patching of the defect has become common, that after-hours repair is infrequent, and that delayed surgical repair has become the preferred approach in many centers. Furthermore, the mean survival rate of 63% indicates that despite decades of individual effort, the CDH problem is far from solved. This highlights the need for a centralized database and cooperative multicenter studies in the future.

Liquid ventilation in adults, children, and full-term neonates

We evaluated the safety and efficacy of partial liquid ventilation in a series of 19 adults, children, and neonates who were in respiratory failure and on extracorporeal life support. During partial liquid ventilation, the alveolar-arterial oxygen difference decreased from 590 (SE 25) to 471 (42) mm Hg (p = 0.0002) and static pulmonary compliance increased from 0.18 (0.04) to 0.29 (0.04) mL cm H2O-1 kg-1 (p = 0.0002). 11 patients (58%) survived. These preliminary data suggest that partial liquid ventilation can be safely used in patients with severe respiratory failure and may improve lung function.

Initial experience with partial liquid ventilation in pediatric patients with the acute respiratory distress syndrome

OBJECTIVE Liquid ventilation with perfluorocarbon previously has not been reported in pediatric patients with respiratory failure beyond the neonatal period. We evaluated the technique of partial liquid ventilation in six pediatric patients with the acute respiratory distress syndrome of sufficient severity to require extracorporeal life support (ECLS). DESIGN This study was a noncontrolled, phase I/II experimental study with a single group pretest/posttest design. SETTING All studies were performed at a tertiary, pediatric referral hospital at the University of Michigan Medical School. PATIENTS Six pediatric patients, from 8 wks to 5 1/2 yrs of age, with severe respiratory failure requiring ECLS to support gas exchange. INTERVENTIONS After 2 to 9 days on ECLS, perfluorocarbon was administered into the trachea until the dependent zone of each lung was filled. The initial administered was 12.9 +/- 2.3 mL/kg (range 5 to 20). Gas ventilation of the perfluorocarbon-filled lungs (partial liquid ventilation) was then performed. The perfluorocarbon dose was repeated daily for a total of 3 to 7 days, with a cumulative dose of 45.2 +/- 6.1 mL/kg (range 30 to 72.5). MEASUREMENTS AND MAIN RESULTS All measurements of native gas exchange were made during brief periods of discontinuation of ECLS and include PaO2 and the alveolar-arterial oxygen gradient, P(A-a)O2. Static pulmonary compliance, corrected for weight, was also measured directly. The mean PaO2 increased from 39 +/- 6 to 92 +/- 29 torr (5.2 +/- 0.8 to 12.2 +/- 3.9 kPa) over the 96 hrs after the initial dose (p = .021 by repeated-measures analysis of variance). The average P(A-a)O2 decreased from 635 +/- 10 to 499 +/- 77 torr (84.7 +/- 1.3 to 66.5 +/- 10.3 kPa) over the same time period (p = .059), while the mean static pulmonary compliance (normalized for patient weight) increased from 0.12 +/- 0.02 to 0.28 +/- 0.08 mL/cm H2O/kg (p = .01). All six patients survived. Complications potentially associated with partial liquid ventilation were limited to pneumothoraces in two of six patients. CONCLUSIONS Perfluorocarbon may be safely administered into the lungs of pediatric patients with severe respiratory failure on ECLS and may be associated with improvement in gas exchange and pulmonary compliance.

Defect size determines survival in infants with congenital diaphragmatic hernia

OBJECTIVES. Congenital diaphragmatic hernia is a significant cause of neonatal mortality. The objective of this study was to evaluate the clinical factors associated with death in infants with congenital diaphragmatic hernia by using a large multicenter data set. METHODS. This was a prospective cohort study of all liveborn infants with congenital diaphragmatic hernia who were cared for at tertiary referral centers belonging to the Congenital Diaphragmatic Hernia Study Group between 1995 and 2004. Factors thought to influence death included birth weight, Apgar scores, size of defect, and associated anomalies. Survival to hospital discharge, duration of mechanical ventilation, and length of hospital stay were evaluated as end points. RESULTS. A total of 51 centers in 8 countries contributed data on 3062 liveborn infants. The overall survival rate was 69%. Five hundred thirty-eight (18%) patients did not undergo an operation and died. The defect size was the most significant factor that affected outcome; infants with a near absence of the diaphragm had a survival rate of 57% compared with infants having a primary repair with a survival rate of 95%. Infants without agenesis but who required a patch for repair had a survival rate of 79% compared with primary repair. CONCLUSIONS. The size of the diaphragmatic defect seems to be the major factor influencing outcome in infants with congenital diaphragmatic hernia. It is likely that the defect size is a surrogate marker for the degree of pulmonary hypoplasia. Future research efforts should be directed to accurately quantitate the degree of pulmonary hypoplasia or defect size antenatally. Experimental therapies can then be targeted to prospectively identify high-risk patients who are more likely to benefit.

Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

ObjectiveThe authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BackgroundThe efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). MethodsA stable model of lung injury was induced in 12 young sheep weighing 16.4 ± 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bjjugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. Main FindingsPhysiologic shunt (Qps/Q1) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 ± 10%; GV = 93 ± 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (Cγ) was significantly increased in the LV group when compared with the GV group (LV = 1.04 ± 0.19 mL/cm H2O/kg; GV = 0.41 ± 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50− to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV =14 ± 5 mL/kg/min; GV = 87 ± 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals.

Prenatal diagnosis of congenital cystic adenomatoid malformation and its postnatal presentation, surgical indications, and natural history

BACKGROUND/PURPOSE Regression of a cystic adenomatoid malformation (CAM) in a fetus is well described. Little, however, is known about the postnatal course of these infants. This study attempts to correlate the prenatal course of CAMs with postnatal symptoms, radiological manifestations, and need for surgery. METHODS The clinical course of patients with a CAM diagnosed prenatally were retrospectively reviewed. Inclusion in the study required a prenatal ultrasound scan documenting a CAM. RESULTS Over 10 years, 14 patients with a CAM were diagnosed prenatally. Six (43%) showed a partial in utero regression. Four patients were symptomatic at birth and underwent a resection as newborns. Ten patients were asymptomatic at birth, and eight of these had normal chest x-rays. Elective resection has been performed in 3 of these 10, and two additional children are scheduled to undergo an excision near 1 year of age. The remaining five patients have undergone follow-up nonoperatively for a mean of 36 +/- 15 months. Of the seven asymptomatic patients not undergoing immediate surgery, only one has shown a slight postnatal regression, despite five of these showing regression in utero. None have become symptomatic. CONCLUSIONS The results suggest that regression of a CAM on prenatal ultrasound scan is common, but this process does not continue after birth. A normal chest x-ray does not indicate complete regression of a CAM; a computed tomography (CT) scan is required to evaluate such patients, and will generally demonstrate a CAM. Asymptomatic patients with a CAM may be followed up nonoperatively with no apparent adverse effects. The decision and timing of an excision in an asymptomatic patient remains controversial among pediatric surgeons.

A review of 100 patients transported on extracorporeal life support.

Between May 1990 and January 1999, 100 patients (68 adult, 32 pediatric) with severe respiratory or cardiac instability were successfully transported to the University of Michigan Medical Center on extracorporeal life support. Diagnoses included adult respiratory distress syndrome (n = 78), cardiac failure (n = 7), sepsis (n = 7), asthma (n = 5), respiratory distress syndrome (of newborn) (n = 2), and airway compromise (n = 1). Of the patients, 53 were supported with venovenous bypass and 47 with venoarterial bypass. Patients were transported by ground ambulance (n = 80), helicopter (n = 15), or fixed-wing aircraft (n = 5). The median transport distance was 44 miles (range 2–790 miles), and the median transport time was 5 hours and 30 minutes (range: 1 h 33 min to 16 h 6 min). Sixty-six patients (66%) survived to discharge. One death occurred during cannulation, and two patients died before cannulation began. Complications that occurred during transport included 10 cases of electrical failure, 3 cases of circuit tubing leakage, and 1 case each of circuit rupture, membrane lung thrombosis, and membrane lung leakage. None of the complications occurring during transport had an adverse effect on outcome. We conclude that the long distance transport of patients on extracorporeal life support can be safely accomplished and is an effective option for the unstable patient with severe respiratory or cardiac failure.

Enterocolitis associated with Hirschsprung's disease: A clinical-radiological characterization based on 168 patients

The enterocolitis associated with Hirschsprungs disease (HD) has not been clearly characterized. This study was undertaken to analyze the clinical and radiological findings of Hirschsprungs enterocolitis (HEC) in 168 patients treated from July 1974 through October 1992. HEC occurred in 57 patients (33.9%), either preoperatively (13; 7.7%) or postoperatively (36; 21.4%). In eight patients (4.8%), it occurred pre- and postoperatively. The number of bouts of HEC per patient ranged from one to six (mean, 2.2). The major presenting features were abdominal distension (83%), explosive diarrhea (69%), vomiting (51%), fever (34%), lethargy (27%), rectal bleeding (5%), and colonic perforation (2.5%). There were no deaths directly related to HEC. The analysis of 150 plain x-rays of the abdomen, taken at the onset of HEC or in between bouts, showed that colonic dilatation was the most sensitive radiological finding (90% sensitivity), but it had poor specificity (24%). However, an intestinal cutoff sign (gaseous intestinal distension with abrupt cutoff at the level of the pelvic brim) was both sensitive (74%) and specific (86%) for HEC. Barium enema was of limited value in the diagnosis of HEC bouts because most of the radiographic findings persisted for prolonged periods after cessation of such bouts. The authors conclude that (1) HEC can be characterized as abdominal distension and explosive diarrhea associated with the intestinal cutoff sign and (2) the occurrence of explosive diarrhea in any patient with HD is suggestive of HEC, even in the absence of systemic symptoms, and should be treated to avoid the morbidity and potential mortality of HEC.

Extracorporeal life support in pulmonary failure after trauma

OBJECTIVE To present a series of 30 adult trauma patients who received extracorporeal life support (ECLS) for pulmonary failure and to retrospectively review variables related to their outcome. METHODS In a Level I trauma center between 1989 and 1997, ECLS with continuous heparin anticoagulation was instituted in 30 injured patients older than 15 years. Indication was for an estimated mortality risk greater than 80%, defined by a PaO2: FIO2 ratio less than 100 on 100% FIO2, despite pressure-mode inverse ratio ventilation, optimal positive end-expiratory pressure, reasonable diuresis, transfusion, and prone positioning. Retrospective analysis included demographic information (age, gender, Injury Severity Score, injury mechanism), pulmonary physiologic and gas-exchange values (pre-ECLS ventilator days [VENT days], PaO2:FIO2 ratio, mixed venous oxygen saturation [SvO2], and blood gas), pre-ECLS cardiopulmonary resuscitation, complications of ECLS (bleeding, circuit problems, leukopenia, infection, pneumothorax, acute renal failure, and pressors on ECLS), and survival. RESULTS The subjects were 26.3+/-2.1 years old (range, 15-59 years), 50% male, and had blunt injury in 83.3%. Pulmonary recovery sufficient to wean the patient from ECLS occurred in 17 patients (56.7%), and 50% survived to discharge. Fewer VENT days and more normal SvO2 were associated with survival. The presence of acute renal failure and the need for venoarterial support (venoarterial bypass) were more common in the patients who died. Bleeding complications (requiring intervention or additional transfusion) occurred in 58.6% of patients and were not associated with mortality. Early use of ECLS (VENT days < or = 5) was associated with an odds ratio of 7.2 for survival. Fewer VENT days was independently associated with survival in a logistic regression model (p = 0.029). Age, Injury Severity Score, and PaO2:FIO2 ratio were not related to outcome. CONCLUSION ECLS has been safely used in adult trauma patients with multiple injuries and severe pulmonary failure. In our series, early implementation of ECLS was associated with improved survival. Although this may represent selection bias for less intractable forms of acute respiratory distress syndrome, it is our experience that early institution of ECLS may lead to improved oxygen delivery, diminished ventilator-induced lung injury, and improved survival.