Distribution dynamics of perfluorocarbon delivery to the lungs: an intact rabbit model.

Motivated by the goal of understanding how to most homogeneously fill the lungs with perfluorocarbon for liquid ventilation, we investigate the transport of liquid instilled into the lungs using an intact rabbit model. Perfluorocarbon is instilled into the trachea of the ventilated animal. Radiographic images of the perfluorocarbon distribution are obtained at a rate of 30 frames/s during the filling process. Image analysis is used to quantify the liquid distribution (center of mass, spatial standard deviation, skewness, kurtosis, and indicators of homogeneity) as time progresses. We compare the distribution dynamics in supine animals to those in upright animals for three constant infusion rates of perfluorocarbon: 15, 40, and 60 ml/min. It is found that formation of liquid plugs in large airways, which is affected by posture and infusion rate, can result in a more homogeneous liquid distribution than gravity drainage alone. The supine posture resulted in more homogeneous filling of the lungs than did upright posture, in which the lungs tend to fill in the inferior regions first. Faster instillation of perfluorocarbon results in liquid plugs forming in large airways and, consequently, more uniform distribution of perfluorocarbon than slower instillation rates in the upright animals.

The dependency of expiratory airway collapse on pump system and flow rate in liquid ventilated rabbits.

PURPOSE: To evaluate the influence of pump system and flow pattern on expiratory airway collapse (EAC) in total perfluorocarbon ventilation. - METHODS: Prospective, controlled, randomized animal trial for determination of (1) post-mortem changes by repeated expiration procedures (EP) with a constant flow piston pump (PP) before and after sacrifice (n = 8 rabbits), (2) differences between pump systems by subjecting animals to both PP and roller pump (RP) circuits for expiration (n = 16 rabbits). EP were performed using a servo-controlled shut-off at airway pressures < 25 cm H subset 2O randomly with either pump at different flows. - RESULTS: Expired volumes before and after sacrifice were not significantly different. PP and RP revealed identical mean flows, while significantly more liquid was drained using PP (p<0.05). Increasing differences towards higher flow rates indicated profound flow pulsatility in RP. - CONCLUSIONS: (1) post-mortem changes in expired volumes are not significant, (2) EAC is related to flow rate and pump system; (3) relationship between expiratory flow rate and drainable liquid volume is linear inverse; (4) PP provides higher drainage than RP. - SUMMARY STATEMENT: Expiratory airway collapse is related to flow rate and pump system, post mortem changes in expirable volumes are not significant. Relationship between expiratory flow rate and drainable liquid volume is linear inverse, piston pump expiration provides higher drainage volumes than roller pump expiration.

Recurrence after laparoscopic and open Nissen fundoplication: a comparison of the mechanisms of failure.

BACKGROUND: Laparoscopic Nissen fundoplication as treatment for gastroesophageal reflux disease (GERD) in adults has a reported recurrence rate of 2-17%. We investigated the rates and mechanisms of failure after laparoscopic Nissen fundoplication in children. METHODS: All patients who underwent a laparoscopic Nissen fundoplication for GERD and who subsequently required a redo Nissen were reviewed (n = 15). The control group consisted of the most recent 15 patients who developed recurrent GER after an open Nissen, fundoplication. RESULTS: Between 1994 and 2000, laparoscopic Nissen fundoplication was performed in 179 patients. Fifteen patients (8.7%) underwent revision. The mechanisms of failure were herniation in four patients, wrap dehiscence in four, a too-short wrap in three, a loosened wrap in two, and other reasons in two. The reoperation was performed laparoscopically in five patients (33%). The failure mechanisms were different in the open patients: eight were due to slipped wraps; three to dehiscences; and two to herniations. CONCLUSION: The failure rate after laparoscopic Nissen is acceptably low. A redo laparoscopic Nissen can be performed safely after an initial laparoscopic approach.

An artificial lung reduces pulmonary impedance and improves right ventricular efficiency in pulmonary hypertension.

OBJECTIVE: Artificial lungs may have a role in supporting patients with end-stage lung disease as a bridge or alternative to lung transplantation. This investigation was performed to determine the effect of an artificial lung, perfused by the right ventricle in parallel with the pulmonary circulation, on indices of right ventricular load in a model of pulmonary hypertension. METHODS: Seven adult male sheep were connected to a low-resistance membrane oxygenator through conduits anastomosed end to side to the pulmonary artery and left atrium. Banding of the distal pulmonary artery generated acute pulmonary hypertension. Data were obtained with and without flow through the device conduits. Outcome measures of right ventricular load included hemodynamic parameters, as well as analysis of impedance, power consumption, wave reflections, cardiac efficiency, and the tension-time index. RESULTS: The model of pulmonary hypertension increased all indices of right ventricular load and decreased ventricular efficiency. Allowing flow through the artificial lung significantly reduced mean pulmonary artery pressure, zero harmonic impedance, right ventricular power consumption, amplitude of reflected waves, and the tension-time index. Cardiac efficiency was significantly increased. CONCLUSIONS: An artificial lung perfused by the right ventricle and applied in parallel with the pulmonary circulation reduces ventricular load and improves cardiac efficiency in the setting of pulmonary hypertension. These data suggest that an artificial lung in this configuration may benefit patients with end-stage lung disease and pulmonary hypertension with right ventricular strain.

Exposure to perflubron is associated with decreased Syk phosphorylation in human neutrophils.

Liquid ventilation with perflubron is associated with reduced neutrophil recruitment into the lung during acute injury. Perflubron also reduces chemotactic responses, the respiratory burst, and cytokine production in neutrophils and in alveolar macrophages in vitro. In the current studies, the effect of perflubron on neutrophil chemotaxis to formyl-Met-Leu-Phe (fMLP) and phagocytosis of opsonized sheep erythrocytes (EA) correlated with decreased phosphorylation of Syk, an important intracellular second messenger in pathways regulating neutrophil functional responses. Brief (5 min) exposure of neutrophils to perflubron resulted in a dose-dependent reduction in chemotaxis to fMLP and reduced phagocytosis of EA but no apparent morphological changes as seen by electron microscopy. Concurrently, there was a reduction in both total cytosolic tyrosine phosphorylation and Syk phosphorylation. Binding studies indicated that this effect was neither a result of impaired ligand-receptor affinity nor a change in the number of fMLP receptors available on the neutrophil surface. These results suggest that perflubron nonspecifically affects cellular activation as measured by tyrosine phosphorylation perhaps by interfering with transmembrane signal transduction.

Prevention of ventilator-induced lung injury with partial liquid ventilation.

BACKGROUND/PURPOSE: Pulmonary injury from mechanical ventilation has been attributed to application of excess alveolar pressure (barotrauma) or volume (volutrauma). The authors questioned whether partial liquid ventilation (gas ventilation of the perfluorocarbon filled lung, PLV) would reduce ventilator-induced lung injury. METHODS: A tracheostomy tube and carotid artery catheter were placed in anesthetized Sprague-Dawley rats (500 +/- 50 g). Bovine serum albumin (BSA) labeled with Iodine (I) 125 was administered intraarterially. Ventilation with tidal volume (TV) of 5 mL/kg was initiated. The rats were then selected randomly to a 30-minute experimental period of one of the following ventilation protocols: continued atraumatic gas ventilation (GV, TV, 5 mL/kg; n = 10); atraumatic gas ventilation combined with intratracheal administration of 10 mL/kg perfluorocarbon (GV-PLV, TV, 5 mL/kg, n = 10); barotrauma (BT, peak inspiratory pressure [PIP], 45 cm H(2)O; n = 10); barotrauma with PLV (BT-PLV, PIP, 45 cm H(2)O; n = 8); volutrauma (VT, TV, 30 mL/kg; n = 8); or volutrauma with PLV (VT-PLV, TV, 30 mL/kg; n = 10). Animals were killed and the amount of radiolabeled BSA in both lungs was measured and normalized to the counts in 1 mL of blood from that animal (injury index). Data were analyzed by analysis of variance (ANOVA) with post-hoc t test comparison between groups. RESULTS: There was a significant difference in the (125)I-BSA injury index when all groups were compared (P <.001 by ANOVA). Post-hoc analysis showed a significant decrease in the injury index when comparing BT versus BT-PLV (P =.024) and VT versus VT-PLV (P =.014). CONCLUSION: (125)I-BSA leak produced during high-pressure or high-volume mechanical ventilation is reduced by partial liquid ventilation.

Continuous intrapulmonary distension with perfluorocarbon accelerates lung growth in infants with congenital diaphragmatic hernia: initial experience.

BACKGROUND/PURPOSE: The authors have shown previously in an animal model that neonatal lung growth can be accelerated by continuous intrapulmonary distension with a perfluorocarbon (PFC). The authors now describe a preliminary clinical experience with this therapeutic concept in a select group of infants with congenital diaphragmatic hernia (CDH). METHODS: Neonates with very high predicted mortality rate caused by CDH had their lungs completely filled with PFC while on extracorporeal life support (ECLS); (n = 5). A continuous positive pressure of 7 to 10 cm H2O was maintained via the endotracheal tube for 3 to 7 days (mean, 5.6 +/- 0.87 days). The areas of both lungs (L) then were measured daily from digitized chest x-rays and divided by the area of the corresponding L1 vertebrae (V), to create an L/V index, so as to control for variable roentgenographic techniques. Immediately after removal of PFC, blood gas data were collected off ECLS. RESULTS: At the end of continuous pulmonary distension, all patients showed improvements in oxygenation and ventilation. The ipsilateral lungs showed significant increase of the L/V index with time (P =.003) and of L/V's daily change (P <.0001), suggesting accelerated lung growth. Overall survival rate was 40% (2 of 5). Of the 3 patients that had 7 days of distension, 2 survived. CONCLUSIONS: Continuous intrapulmonary distension with PFC for up to 1 week accelerated ipsilateral lung growth, improved gas exchange, and increased survival of CDH infants with profound pulmonary hypoplasia marooned on ECLS. Additional trials of PFC-based pulmonary distension in similar infants are warranted.

Detrimental effects of complement activation in hemorrhagic shock.

The complement system has been implicated in early inflammatory events and a variety of shock states. In rats, we measured complement activation after hemorrhage and examined the hemodynamic and metabolic effects of complement depletion before injury and worsening of complement activation after hemorrhage and resuscitation [with a carboxypeptidase N inhibitor (CPNI), which blocks the clearance of C5a]. Rats were bled to a mean arterial pressure of 30 mmHg for 50 min and were then resuscitated for 2 h. Shock resulted in significant evidence of complement consumption, with serum hemolytic activity being reduced by 33% (P < 0.05). Complement depletion before injury did not affect hemorrhage volume (complement depleted = 28 +/- 1 ml/kg, complement intact = 29 +/- 1 ml/kg, P = 0.74) but improved postresuscitation mean arterial pressure by 37 mmHg (P < 0.05) and serum bicarbonate levels (complement depleted = 22 +/- 3 meq/ml, complement intact = 13 +/- 8 meq/ml, P < 0.05). Pretreatment with CPNI was lethal in 80% of treated animals vs. the untreated hemorrhaged group in which no deaths occurred (P < 0.05). In this model of hemorrhagic shock, complement activation appeared to contribute to progressive hypotension and metabolic acidosis seen after resuscitation. The lethality of CPNI during acute blood loss suggests that the anaphylatoxins are important in the pathophysiological events involved in hemorrhagic shock.

A novel stable reproducible model of hepatic failure in canines.

BACKGROUND: Stable and reproducible large animal models of hepatic failure, which allow the assessment of liver-assist devices, are not available. Our objective was to develop a physiologically stable animal model of hepatic failure on which the safety and efficacy of an extracorporeal liver-assist device can be tested. We hypothesized that a surgical model which consists of an end-to-side portocaval shunt combined with common bile duct ligation and transection would create hepatic failure with: (1) elevations in amino transferases, total bilirubin, and ammonia; (2) a decrease in the ratio of branched chain to aromatic amino acids; and (3) histologic evidence of hepatic injury. METHODS: Eleven mongrel dogs underwent common bile duct transection and an end-to-side portocaval shunt. Aminotransferases (AST, ALT), total bilirubin, ammonia, and branched chain and aromatic amino acids were measured prior to operation (baseline) and after 9 days. A necropsy was performed on Postoperative Day 9 and liver biopsies were obtained for histology. RESULTS: By Postoperative Day 9, AST, ALT, total bilirubin, and ammonia values were significantly elevated compared to baseline (P < 0.02). The ratio of branched chain to aromatic amino acids was significantly reduced compared to baseline (P < 0.003). There was histologic evidence of cholestasis and inflammation. CONCLUSION: Portocaval shunt with common bile duct transection produces liver failure with elevations in aminotransferases, total bilirubin, and ammonia, a decreased branched chain to aromatic amino acid ratio, and histologic inflammation. Unlike ischemic or chemically induced models of liver failure, the dogs were hemodynamically and neurologically stable. This model can be used to test the safety and efficacy of liver-assist devices aimed at temporizing the detoxification functions of the failing liver.

Does perfluorocarbon deoxygenate during partial liquid ventilation?

Perfluorocarbons accumulate in the dependent regions of the lungs, which may result in regional hypoxia if ventilation with oxygen is insufficient to oxygenate the dependent perfluorocarbon-filled alveoli. In this issue of Critical Care, Max et al present data that demonstrate a decrease in arterial oxygen tension (PaO2) at 30 min compared to that observed at 5 min after administration of FC 3280. These data suggest failure of on-going ventilation/oxygenation to support the initial increase in PaO2 attributed to the oxygen dissolved in the administered perfluorocarbon. Studies such as this one demonstrate that development of the optimal partial liquid ventilation (PLV) technique is ongoing.

Effect of rate and inspiratory flow on ventilator-induced lung injury.

BACKGROUND: We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (It) and reducing inspiratory flow on the development of ventilator-induced lung injury. METHODS: Forty sheep weighing 24.6+/-3.2 kg were ventilated for 6 hours with one of five strategies (FIO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PIP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, It = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8. RESULTS: Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38+/-18%, LIFR = 19+/-6%, p < 0.001), reduced histologic injury (HiPIP = 14+/-0.9, LIFR = 2.2+/-0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90+/-49, LIFR = 7.6+/-3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3+/-8.5%, LIFR = 40.8+/-17.4%,p < 0.001). CONCLUSIONS: High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or It. Reduction of inspiratory flow at similar PIP provides pulmonary protection.

An economic evaluation of sonographic examination of children with suspected appendicitis.

BACKGROUND/PURPOSE: Appendicitis is the most common surgical emergency presenting in the pediatric population. Approximately one third of these patients present with equivocal signs and symptoms frequently resulting in inpatient observation or additional diagnostic investigation. Although sonographic examination of patients with suspected appendicitis has been shown to be a highly accurate diagnostic modality, the cost effectiveness of this technology in the pediatric population has not been addressed. The economic value of this examination can be evaluated using a structured decision analysis. METHODS: The authors constructed a decision analysis model of treatment strategies for 2 groups of patients with a suspected diagnosis of acute appendicitis. Patients were categorized as either presenting with a "definitive acute abdomen" or "equivocal examination." Data drawn from published literature reports of the sensitivity and specificity of ultrasound, institution-specific cost data, and expert judgment were used to construct 2 decision trees. These data were used to determine the least costly diagnostic strategy for each group of patients, and sensitivity analysis performed to assess the robustness of the conclusions. RESULTS: The use of ultrasonography in patients with "an acute abdomen" is not cost efficient and results in average additional cost of $234 per patient. In patients with equivocal diagnoses who are discharged from the emergency room after a negative ultrasound examination finding results in an average cost savings of $260 when compared with admission and observation. Patients who are discharged without examination incur an average additional cost of $373 as a result of the high cost of a missed diagnosis resulting in a perforated appendix. CONCLUSION: The use of ultrasonography can be recommended for children with suspected appendicitis and equivocal examinations who are discharged from the emergency room after a negative examination result.

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.

The response to splenectomy in pediatric patients with idiopathic thrombocytopenic purpura who fail high-dose intravenous immune globulin.

BACKGROUND: A recent article by Law et al concluded that patients with idiopathic thrombocytopenic purpura (ITP) who have a poor response to intravenous immune globulin (IgG) are unlikely to have a good or excellent response to surgical splenectomy. METHODS: The authors studied retrospectively 23 pediatric patients age 11.7 +/- 1.0 years with ITP who had been treated with IgG before undergoing splenectomy. As in the aforementioned article, the responses to the 2 treatments were classified on the basis of the platelet count as poor (<50,000/mm3), good (50,000 to 150,000/mm3), or excellent (>150,000/mm3). For patients who received multiple IgG treatments, both initial and final treatment responses were analyzed. RESULTS: Sixteen patients had an excellent or good initial response to IgG. Of these 16 patients, 14 had an excellent or good response to splenectomy. Among the 7 patients who had a poor response to IgG there were 3 who had an excellent or good response to splenectomy (43%), and 4 patients who had a poor response to splenectomy. A good or excellent response to initial treatment with IgG was associated with a significant probability of a good or excellent response to splenectomy (P = .045). CONCLUSIONS: A good or excellent response to IgG may be predictive of a favorable response to splenectomy. However, a poor response to IgG does not preclude a satisfactory response to splenectomy in pediatric patients with ITP.

Development and application of a double-piston configured, total-liquid ventilatory support device.

OBJECTIVE: Perfluorocarbon liquid ventilation has been shown to enhance pulmonary mechanics and gas exchange in the setting of respiratory failure. To optimize the total liquid ventilation process, we developed a volume-limited, time-cycled liquid ventilatory support, consisting of an electrically actuated, microprocessor-controlled, double-cylinder, piston pump with two separate limbs for active inspiration and expiration. DESIGN: Prospective, controlled, animal laboratory study, involving sequential application of conventional gas ventilation, partial ventilation (PLV), and total liquid ventilation (TLV). SETTING: Research facility at a university medical center. SUBJECTS: A total of 12 normal adult New Zealand rabbits weighing 3.25+/-0.1 kg. INTERVENTIONS: Anesthestized rabbits were supported with gas ventilation for 30 mins (respiratory rate, 20 cycles/min; peak inspiratory pressure, 15 cm H2O; end-expiratory pressure, 5 cm H2O), then PLV was established with perflubron (12 mL/kg). After 15 mins, TLV was instituted (tidal volume, 18 mL/kg; respiratory rate, 7 cycles/min; inspiratory/expiratory ratio, 1:2 cycles/min). After 4 hrs of TLV, PLV was re-established. MEASUREMENTS AND MAIN RESULTS: Of 12 animals, nine survived the 4-hr TLV period. During TLV, mean values +/- SEM were as follows: PaO2, 363+/-30 torr; PaCO2, 39+/-1.5 torr; pH, 7.39+/-0.01; static peak inspiratory pressure, 13.2+/-0.2 cm H2O; static endexpiratory pressure, 5.5+/-0.1 cm H2O. No significant changes were observed. When compared with gas ventilation and PLV, significant increases occurred in mean arterial pressure (62.4+/-3.5 torr vs. 74.0+/-1.2 torr) and central venous pressure (5.6+/-0.7 cm H2O vs. 7.8+/-0.2 cm H2O) (p < .05). CONCLUSIONS: Total liquid ventilation can be performed successfully utilizing piston pumps with active expiration. Considering the enhanced flow profiles, this device configuration provides advantages over others.

Reduced platelet activation and thrombosis in extracorporeal circuits coated with nitric oxide release polymers.

OBJECTIVE: To determine whether the use of nitric oxide (NO)-releasing polymers coated onto the inner surface of extracorporeal circuits can reduce platelet consumption and activation in the absence of systemic heparinization using a rabbit model of venovenous extracorporeal circulation. DESIGN: Prospective, controlled trial. SETTING: Research laboratory at an academic medical institution. SUBJECTS: New Zealand White Rabbits. INTERVENTIONS: Anesthetized, tracheotomized, and ventilated New Zealand White rabbits were injected with freshly prepared, 111In(oxine)3 labeled single donor platelets through the external jugular vein. After baseline measurements, these animals were placed on venovenous extracorporeal circulation through a 1-m control circuit or NO test circuit for 4 hrs at a blood flow rate of 109-118 mL/min via roller pump. Four groups were studied: systemically heparinized control circuits, systemically heparinized NO test circuits, nonheparinized control circuits, and nonheparinized NO test circuits. Platelet counts, fibrinogen levels, and plasma free indium levels were measured hourly. Circuits were rinsed and retained for gamma counting after the 4-hr run or when the circuit clotted. Four animals, one from each group, did not receive radiolabeled platelets so that the circuits could be preserved for scanning electron microscopic examination after the 4-hr study. MEASUREMENTS AND MAIN RESULTS: Platelet consumption was significantly reduced in both the heparinized and nonheparinized NO test groups when compared with the controls (p < .0001 and p < .0004, respectively). Platelet adhesion to the extracorporeal circuits was significantly reduced in the nonheparinized test circuits when compared with the controls (p < .05). Scanning electron microscopic examination of the circuits revealed that in the absence of heparin and in the presence of a NO-releasing surface, platelets retained their spherical nonactivated shape. CONCLUSIONS: The incorporation of NO into the surface of extracorporeal circuits reduces platelet consumption and eliminates the need for systemic heparinization in a rabbit model of extracorporeal circulation.

Use of the placenta as an artificial lung.

Oxygen transfer across a single cotyledon of the human placenta was assessed by using three different perfusates in the maternal circuit: 1) M-199 culture medium, 2) human adult red blood cells (RBCs), and 3) perflubron. These maternal circuit perfusates were oxygenated with a membrane oxygenator. RBCs were perfused on the fetal side of the circuit and samples were taken preplacenta and postplacenta for each maternal perfusate. PO2 and PCO2 were measured and O2 transfer was calculated for each maternal perfusate. O2 transfer per single cotyledon (mean +/- SE) was 0.18 +/- 0.04, 0.20 +/- 0.03, and 0.15 +/- 0.05 ccO2/min when using: 1) M-199, 2) RBCs, and 3) perflubron, respectively. O2 transfer per kilogram of placental tissue was 13.08 +/- 2.78, 14.57 +/- 2.05, and 10.43 +/- 3.79 ccO2/kg per minute when using: 1) M-199, 2) RBCs, and 3) perflubron, respectively. When extrapolated to the individual weights of the entire placenta, the O2 transfer was 9.15 +/- 1.95, 10.20 +/- 1.43, and 7.30 +/- 2.65 when using: 1) M-199, 2) RBCs, and 3) perflubron, respectively. We conclude from these data that O2 transfer can be accomplished during placental perfusion. Larger studies are required to differentiate efficacy among the three maternal circuit perfusates.

Historical changes in the postoperative treatment of appendicitis in children: impact on medical outcome.

BACKGROUND/PURPOSE: The introduction of managed care in the 1980s caused increased pressure to reduce costs for hospitalized patients. The authors hypothesized that these market forces have resulted in a decreased hospital stay and utilization of sophisticated diagnostic testing in children treated for appendicitis. If true, the impact of this paradigm shift on patient outcome is unknown. METHODS: Hospital records for 913 pediatric patients treated for appendicitis from 1974 to 1998 were reviewed retrospectively. Patients were stratified into those with perforated appendicitis (PA) and nonperforated appendicitis (NPA). Demographics, perioperative hospital course, diagnostic testing, complications, and long-term outcomes were analyzed after stratification into time intervals. RESULTS: Over time, children with NPA were treated with shorter antibiotic courses (P<.05) and were placed on a regular diet earlier (P<.05). These changes in treatment resulted in an earlier discharge (P<.05). The amount of time to become afebrile with a normal white blood cell count (WBC) did not change over time. Children with PA exhibited similar results with shorter antibiotic courses (P<.05), earlier dietary intake (P<.05) and earlier hospital discharge (P<.05) over time. In all children with appendicitis there was no significant difference in the rate of wound infections, abscesses requiring drains, readmission, or reoperations overtime. The utilization of abdominal radiographs (83%) and ultrasonography (USN; 40%) was high and remained unchanged over time. Utilization of computed tomography (CT scan) was low (4.3%) in the early decades and was not used as a preoperative test from 1991 to 1994. Given the high diagnostic accuracy of a pediatric surgeon for this disease, Bayesian analysis indicates that USN utilization rates should be 15%. CONCLUSIONS: The market pressures of managed care have resulted in a new treatment paradigm with an earlier discharge of all children with appendicitis. There has been no concomitant increase in the complication rate in either group as a result of this paradigm shift. Bayesian analysis indicates that USN and abdominal radiographs are overutilized in our institution.

Extracorporeal life support: the University of Michigan experience.

The University of Michigan experience with extracorporeal life support (ECLS) in 1000 consecutive patients between 1980 and 1998 is the largest series at one institution in the world. Among this patient population, survival to hospital discharge in moribund patients with respiratory failure was 88% in 586 neonates, 70% in 132 children, and 56% in 146 adults. Survival in moribund patients with cardiac failure was 48% in 105 children and 33% in 31 adults. This article describes the University of Michigan's overall ECLS patient experience, the progression of ECLS from laboratory experiments to clinical application at the bedside, the expansion of the technology to other centers, and current ECLS technology and outcomes. Despite the challenges faced in clinical research in this field, our experience and that of others has shown that ECLS saves lives of patients with acute cardiac or pulmonary failure in a variety of clinical settings.

Predictors of malignancy in childhood peripheral lymphadenopathy.

PURPOSE: The aim of this study was to identify factors associated with malignant etiologies of childhood peripheral lymphadenopathy and to construct a model that may be used to assess the risk of malignancy. METHODS: The medical records of 60 consecutive patients 18 years old or less who underwent peripheral lymph node biopsies were reviewed. RESULTS: Increasing node size, number of sites of adenopathy, and age were associated with an increasing risk of malignancy (P < .05 for all variables). Graphs useful for risk determination were constructed based on these variables. Additional factors associated with malignancy included the presence of supraclavicular adenopathy (P < .01), an abnormal chest x-ray (P < .01), and fixed nodes (P < .01). Variables that were not statistically different between patients with benign and malignant adenopathy included the duration of adenopathy (P = .43), the presence of fever (P = .36), cough (P = .14), splenomegaly (P = .93), skin involvement (P = .39), tenderness (P = .49), and bilateral adenopathy (P = .39). Fluctuance was associated with benign adenopathy (P < .04). CONCLUSIONS: The risk of malignancy increased with increasing size and number of sites of adenopathy and age. Other significant predictors of malignancy included supraclavicular location, an abnormal chest x-ray, and fixed nodes. These data may be used to supplement clinical judgment to predict the risk of malignancy.