The pulmonary and systemic distribution and elimination of perflubron from adult patients treated with partial liquid ventilation.

OBJECTIVE: To assess the pulmonary and systemic distribution and elimination of perflubron (C(8)F(17)Br(1); LiquiVent; Alliance Pharmaceutical; San Diego, CA) during and following the period of partial liquid ventilation. DESIGN: Prospective phase I and II clinical trial. SETTING: Adult surgical ICU. PATIENTS: Eighteen adult patients (mean +/- SEM age, 37.9 +/- 3.4 years) with severe respiratory failure, some of whom required extracorporeal life support (72%), and who were managed with partial liquid ventilation with perflubron. INTERVENTIONS: Perflubron was administered into the trachea, and gas ventilation of the perfluorocarbon-filled lung (partial liquid ventilation) was then performed. Additional doses were administered daily for from 1 to 7 days, with a median cumulative dose of 31 mL/kg (range, 3 to 60 mL/kg). MEASUREMENTS AND MAIN RESULTS: Patient blood samples were evaluated by gas chromatography for serum perflubron levels. Sequential lateral and anteroposterior radiographs were assessed, using a 5-point rating scale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss of perflubron in the expired gas was measured by gas chromatography. Mean serum perflubron levels increased to 0.16 +/- 0.05 mg/dL at 24 h following administration of the initial dose. A mean maximum level of 0.26 +/- 0.05 mg/dL of perflubron was present in the serum 24 h following the administration of the last dose. This level slowly trended downward to 0.18 +/- 0.06 mg/dL over the ensuing 7 days (p = 0.281). Perflubron elimination via expired gas occurred at a mean rate of 9.4 +/- 3.0 mL/h at 1 h, and 1.0 +/- 0.4 mL/h at 48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from 4.2 +/- 0.2 at the time of administration of the last dose, to 2.8 +/- 0.3 at 4 days later (p < 0.001). Perflubron tended to distribute and remain for longer periods in the dependent regions of the lung when compared to the nondependent regions (96-h perflubron fill score: posterior, 3.8 +/- 0.5; anterior, 1.9 +/- 0.4; p = 0.004). CONCLUSIONS: Perflubron is eliminated at a maximum rate of 9.4 +/- 3.0 mL/h by evaporative loss from the airways and is retained in greater amounts in the dependent lung regions when compared to the nondependent lung regions. There is a low but measurable maximum blood concentration of 0.26 +/- 0.05 mg/dL in patients after perflubron administration, which did not decrease significantly after cessation of partial liquid ventilation.

Percutaneous cannulation for pediatric venovenous extracorporeal life support.

BACKGROUND/PURPOSE: The objective of this study was to show the safety and efficacy of a method of percutaneous cannulation for venovenous extracorporeal life support (ECLS) access in nonneonatal (>10 kg) pediatric patients. METHODS: Between June 1992 and October 1998, 26 pediatric patients (age range, 3 to 17 years; weight range, 19 to 100 kg) underwent attempted percutaneous cannulation for venovenous ECLS at our institution. Venous drainage access was attempted using a modified Seldinger technique via the right internal jugular vein (RIJ, n = 22) or right femoral vein (RFV, n = 4). Reinfusion access was attempted via the RFV (n = 19), RIJ (n = 4), or left femoral vein (n = 3). RESULTS: The percutaneous technique was successful in 24 of 26 patients (92.3%). Maximum blood flow during ECLS was 80.1 +/- 30.0 mL/kg/min, generating a postmembrane lung outlet pressure of 138 +/- 54.8 mm Hg. Adequate gas exchange was achieved in all patients, and survival to discharge was 79.2%. There was no procedure-related mortality. Complications potentially related to the percutaneous technique included RIJ thrombosis (n = 1) detected after decannulation and cannula site bleeding (n = 3). CONCLUSION: Percutaneous access may be used safely and effectively for venovenous ECLS in pediatric patients.

Venovenous extracorporeal life support via percutaneous cannulation in 94 patients.

STUDY OBJECTIVE: The objective of this study was to demonstrate the safety and utility of a method of percutaneous access for cannulation of adult patients for venovenous extracorporeal life support (ECLS). DESIGN: A retrospective review of a patient series. SETTING: A surgical ICU at a university teaching hospital. PATIENTS: The study group consisted of 94 adults > 17 years old with respiratory failure who were placed on venovenous ECLS by means of percutaneous cannulation. INTERVENTIONS: The cannulation of the internal jugular and femoral veins (FVs) using the Seldinger technique for venovenous ECLS. MEASUREMENTS AND RESULTS: Between May 1992 and November 1997, we performed percutaneous cannulation for venovenous ECLS in 94 adult patients with respiratory failure. The mean (+/- SD) age was 36.1+/-12.7 years old (range, 17 to 65 years). The mean (+/-SD) weight was 80.7+/-22.3 kg (range, 36 to 156 kg). The right internal jugular vein (RIJV) was used for venous drainage access in all but four cases. The right FV (n = 86), the left FV (n = 3), or the RIJV (n = 4) was utilized for venous reinfusion. The maximum blood flow (+/-SD) during ECLS was 57.6+/-17.5 mL/kg/min (range, 22.4 to 127.8 mL/kg/min), with a postmembrane outlet pressure (+/-SD) of 146+/-43 mm Hg (range, 56 to 258 mm Hg) at the maximum flow rate. There were 11 unsuccessful percutaneous cannulation attempts. In three patients (3%), the complications consisted of arterial injury requiring operative cutdown and repair. In six patients (6%), cannula-site bleeding required pursestring suture reinforcement of the cannula site. One patient died from the perforation of the superior vena cava during cannulation. CONCLUSIONS: Based on these data, we conclude that percutaneous cannulation may be utilized to provide venovenous ECLS in adults.

Mortality is directly related to the duration of mechanical ventilation before the initiation of extracorporeal life support for severe respiratory failure.

OBJECTIVE: To investigate the relationship between the period of mechanical ventilation before extracorporeal life support and survival in patients with respiratory failure. DESIGN: Retrospective review. SETTING: Surgical intensive care unit at a university medical center. PATIENTS: Thirty-six consecutive adult patients with severe respiratory failure managed with extracorporeal life support. INTERVENTIONS: Extracorporeal life support was utilized in 36 acute respiratory failure adult patients with a variety of diagnoses and an estimated mortality rate of > 90%. Management protocols were followed before and during extracorporeal life support. The 36 patients were physiologically similar before extracorporeal life support was initiated: shunt of 48 +/- 17%; F10(2) of 1.0 +/- 0.1; peak inspiratory pressure of 56 +/- 16 cm H2O; positive end-expiratory pressure of 14 +/- 6 cm H2O; and respiratory rate of 23 +/- 10 breaths/ min. Ventilation was utilized for 1 to 17 days before extracorporeal life support. Typical lung rest settings during extracorporeal life support were F10(2) of 0.40, peak inspiratory pressure of 30 cm H2O, positive end-expiratory pressure of 10 cm H2O, and respiratory rate of 6 breaths/min. Death was almost always secondary to end-stage pulmonary failure. MEASUREMENTS AND MAIN RESULTS: Survival (hospital discharge) in these 36 patients was inversely associated with the number of days of preextracorporeal life support ventilation, with a 50% mortality rate predicted by logistic regression after 5 days of mechanical ventilation. The overall survival rate was 18 (50.0%) of 36 patients. CONCLUSIONS: In severe acute respiratory failure treated with lung rest and extracorporeal life support, a predicted 50% mortality rate was associated with 5 days of preextracorporeal life support mechanical ventilation.

Efficacy of perfluorocarbon partial liquid ventilation in a large animal model of acute respiratory failure.

OBJECTIVE: To demonstrate the efficacy of partial perfluorocarbon liquid ventilation in large animal model of acute respiratory failure. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory at a university medical center. SUBJECTS: Ten adult sheep, weighing 53.0 +/- 2.8 kg. INTERVENTIONS: After assessment of baseline physiologic data, acute respiratory failure was induced by right atrial injection of oleic acid (0.2 mL/kg). Five animals (partial liquid ventilation group) underwent sequential intratracheal dosing of 10 mL/kg of perflubron at 30-min intervals to the following cumulative doses: 10, 20, 30, 40, and 50 mL/kg. The remaining five animals were gas ventilated (control group). Physiologic data were assessed at 30-min intervals in both groups for the 2.5-hr experimental period or until death. MEASUREMENTS AND MAIN RESULTS: When compared with control animals, intratracheal perfluorocarbon instillation resulted in significant improvements in arterial oxygen saturation (arterial oxygen saturation after 50 mL/kg: partial liquid ventilation, 96 +/- 3%; control, 55 +/- 8%; p = .001) and physiologic shunt (physiologic shunt after 50 mL/kg dose: partial liquid ventilation, 2 +/- 8%; control, 64 +/- 5%; p = .004). Oxygen delivery improved with perfluorocarbon instillation, but this improvement was not significant. No significant difference in pulmonary compliance was observed during partial liquid ventilation when compared with controls (pulmonary compliance: partial liquid ventilation, 0.43 +/- 0.04 mL/ cm H2O/kg; control, 0.53 +/- 0.03 mL/cm H2O/kg; p = .102). CONCLUSIONS: Partial liquid ventilation with perflubron provides effective improvement in gas exchange in an adult animal model of respiratory failure.

Partial liquid ventilation in a child on extracorporeal life support.

A 14 month old child was referred for management of acute respiratory distress syndrome after aspiration of paraffin lamp oil. Initial management with conventional ventilation and subsequent management with high frequency oscillatory ventilation produced pulmonary air leaks, further compromising clinical management. After initiating extracorporeal life support and low pressure ventilation, pulmonary air leaks subsided. The patient was then successfully managed by a protocol including partial liquid ventilation with perfluorocarbon. This case report details the authors' experience with the first child with respiratory failure to be managed with partial liquid ventilation while on extracorporeal life support.

Partial liquid ventilation in newborn patients with congenital diaphragmatic hernia.

The authors evaluated the safety and efficacy of liquid ventilation with perfluorocarbon in four newborns with congenital diaphragmatic hernia and severe respiratory failure, who were on extracorporeal life support (ECLS). After 2 to 5 days on the ECLS, perflubron was administered into the trachea until the dependent zone of the lung was filled. The first dose was 6 +/- 1 mL/kg (range, 5 to 8 mL/kg). Gas ventilation of the perflubron-filled lung was performed (partial liquid ventilation). The administration of perflubron was repeated daily for 5 to 6 days, with total cumulative doses of 36 +/- 8 mL/kg (range, 26 to 44 mL/kg). A significant increase in PaO(2) (P = .027 by repeated-measures analysis of variance [ANOVA]), a trend toward an increase in arterial oxygen content (P = .052 by repeated-measures ANOVA), and a significant increase in specific static total pulmonary compliance (P = .007 by repeated-measures ANOVA) were observed after administration of the daily dose of perflubron. PaCO(2) data showed a decreasing trend (P = .08 by repeated measures ANOVA). The authors conclude that perflubron can be safely administered into the lungs of newborn patients with congenital diaphragmatic hernia and severe respiratory failure, and it may be associated with improvement in gas exchange and pulmonary compliance.

Partial liquid ventilation provides effective gas exchange in a large animal model.

PURPOSE: The purpose of this study was to show the ability of partial liquid ventilation (PLV) to sustain gas exchange in normal large (50 to 70 kg) adult animals. METHODS: Ten adult sheep (53.7 +/- 2.8 kg) were anesthetized and mechanically ventilated. Sequential dosing of perflubron (LiquiVent, Alliance Pharmaceutical Corp, San Diego, CA) was performed to cumulative doses of 10 mL/kg, 20 mL/kg, 40 mL/kg, and 60 mL/kg. Physiological data were assessed at baseline and after each dose. Five animals were rotated through the left decubitus, right decubitus, supine, and prone positions while five animals remained prone throughout the experiment. RESULTS: PaO2 and PaCO2 did not change significantly from baseline during administration of perflubron except for the PaO2 in rotated animals when supine (rotated-supine PaO2: baseline = 519 +/- 64 mm Hg; 60 mL/kg = 380 +/- 109 mm Hg, P = .0131). In both groups, static lung compliance (CT) decreased steadily with each successive perflubron instillation (nonrotated CT: baseline = 1.55 +/- 0.22 mL/cm H2O/kg; 60 mL/kg = 0.52 +/- 0.10 ml/cmH2O/kg, P = .0003). CONCLUSIONS: These data show that during PLV in this normal animal model, effective gas exchange is sustained and CT decreases with increasing perflubron dose.

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

OBJECTIVE: To evaluate the safety and efficacy of partial liquid ventilation (PLV). DESIGN: Before-after trial. SETTING: The surgical intensive care unit at the University of Michigan, Ann Arbor, from April to December 1994. PATIENTS: A consecutive sample of 10 patients aged 19 to 55 years with the acute respiratory distress syndrome who were receiving extracorporeal life support. INTERVENTION: Perflubron was administered into the trachea until the dependent zone of the lung was filled. Gas ventilation of the perflubron-filled lung was then performed (PLV). Volatilized perflubron replacement was repeated daily for from 1 to 7 days with a median cumulative dose of 38 mL/kg (range, 15 to 62 mL/kg). MAIN OUTCOME MEASURES: Physiologic shunt and static pulmonary compliance. RESULTS: Physiologic shunt decreased from a median of 0.72 (range, 0.37 to 1.0) to 0.46 (range, 0.21 to 0.96) over the 72 hours following initiation of PLV (P = .01 by repeated measures analysis of variance). Static pulmonary compliance corrected for patient weight increased from a median of 0.16 mL/cm H2O per kilogram (range, 0.01 to 0.48 mL/cm H2O per kilogram) to 0.27 mL/cm H2O per kilogram (range, 0.05 to 1.11 mL/cm H2O per kilogram) over the same time period (P = .04 by repeated measures analysis of variance). Overall survival was five (50%) of 10 patients. Complications that were potentially associated with PLV included pneumothorax development in one patient and mucus plug formation in one patient. CONCLUSIONS: Perflubron may be safely administered into the lungs of patients with severe respiratory failure receiving extracorporeal life support and may be associated with improvement in gas exchange and pulmonary compliance.

Partial liquid ventilation with perflubron during extracorporeal life support in adults: radiographic appearance.

PURPOSE: To describe the radiographic appearance of perflubron-filled lungs during partial liquid ventilation (PLV). MATERIALS AND METHODS: Supine chest radiographs (391 anteroposterior, 154 lateral radiographs) were obtained before and after daily perflubron instillation in 13 adults undergoing PLV who were receiving extracorporeal life support. Perflubron distribution, barotrauma, and inability to discern catheters were evaluated. RESULTS: Immediately after instillation of perflubron, opacification of more than two-thirds of the lungs was shown in 12 of 13 patients. A gravity-dependent distribution of perflubron was shown on 146 (95%) of 154 lateral radiographs. Perflubron gradually cleared until it filled less than one-third of the lungs 6.8 days later (range, 2-20 days). In the five survivors, minimal perflubron was visible up to 138 days. In five patients, perflubron increased the visibility of small pneumothoraces present before PLV. Location of intrathoracic catheters was obscured on 44 radiographs. CONCLUSION: Perflubron symmetrically opacifies the lungs in a gravity-dependent distribution during PLV and clears to minimal levels within 3 weeks.

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.

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.

Approach to cervicothoracic neuroblastomas via a trap-door incision.

Neuroblastomas located in the apex of the hemithorax or in the lower cervical region may make complete resection via a cervical or a thoracic approach difficult. The authors recently managed two patients with cervicothoracic neuroblastomas through an approach using the trap-door incision often applied in the setting of vascular trauma. This approach allowed a successful, complete excision of these tumors, which may have otherwise been difficult.

Splenic trauma: value of follow-up CT.

PURPOSE: To determine the value of follow-up computed tomography (CT) after expectant treatment in patients with clinically stable blunt splenic trauma. MATERIALS AND METHODS: Medical records and CT studies for 42 patients were reviewed, and injuries were graded on a scale of 1-6. Patients were divided into three groups: stable patients with no follow-up CT (group 1, n = 14), stable patients with follow-up CT (group 2, n = 22), and symptomatic patients with follow-up (group 3, n = 6). Serial hemoglobin values and clinical findings at follow-up CT were reviewed. RESULTS: All patients in groups 1 and 2 remained clinically stable with good outcomes. In group 3, follow-up CT scans demonstrated worsening condition in four patients (67%), and three of the four had poor outcomes. CONCLUSION: Follow-up CT may be unnecessary in patients with clinically stable splenic trauma.

Resolution of splenic injury after nonoperative management.

Numerous studies have demonstrated success with nonoperative management of splenic injuries in pediatric patients. However, the resolution of the splenic injury has not been previously evaluated. The records of 50 pediatric patients with splenic injuries from blunt trauma treated nonoperatively between 1984 to 1992 were reviewed retrospectively. Abdominal computed tomography (CT) was performed at the time of injury and 6 weeks postinjury in 25 patients. These scans were reviewed and categorized by a modification of a previously reported grading system for parenchymal injury. All patients had healing of the splenic injuries, with complete resolution of the healing process observed at 6 weeks postinjury in 44%. Even those with shattered spleens (n = 6) had consistent improvement in splenic architecture, with resolution of fractures and/or contusions and return of splenic perfusion. Ten (77%) of 13 grade 1 and 2 injuries were completely resolved by the 6-week follow-up examination, whereas only one (8%) of 12 grade 3 to 5 injuries showed radiological resolution of splenic injuries. None of the 25 follow-up CT scans affected clinical decision-making or led to a deviation from the established protocol, which included a 3-month period of reduced activity. All 50 patients did well, without evidence of morbidity, mortality, or complications after return to full activity 3 months postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of extracorporeal life support in the setting of adult cardiorespiratory failure.

The efficacy of extracorporeal life support (ECLS, ECMO) in the management of severe adult cardiorespiratory failure remains controversial. The purpose of this review is to evaluate the authors' institutional experience with ECLS in adult patients. Between 1988 and 1993, 65 moribund patients with respiratory (n = 51) and cardiac (n = 14) failure were supported with ECLS. Criteria for initiation of ECLS were: 90% chance of mortality despite maximal conventional respiratory management, good potential for recovery, and age younger than 60 years. Venovenous bypass was used in 40 and venoarterial in 25 patients. Respiratory management included low rate, low pressure ventilation with an inspired oxygen fraction < or = 0.5 and tracheostomy tube placement. Continuous systemic heparinization was used, maintaining whole blood activated clotting time (ACT) between 180 and 200 sec. Survival data are summarized as follows: pneumonia (n = 25) 56%, adult respiratory distress syndrome (n = 24) 58%, airway support (n = 2) 100%, and cardiac support (n = 14) 29%. The most common complication was bleeding (68%), which was managed in most patients by reduction of anticoagulation or local measures such as packing. Data from survivors and nonsurvivors of ECLS in patients with respiratory failure were compared in an attempt to define prognostic indicators of improved survival. The only prognostic indicator of survival that could be identified was the period of time on the ventilator before the initiation of ECLS (survivors = 3.0 +/- 2.4 days, nonsurvivors = 6.1 +/9- 4.0 days, P < 0.005). It is concluded that ECLS can be a life saving modality for the management of severe adult cardiorespiratory failure. Earlier institution of ECLS in the course of cardiopulmonary failure may improve outcome.