Twenty-year follow-up: an unusual case of nephropathy of antiphospholipid syndrome.

Nephropathy of antiphospholipid antibody syndrome (NAPS) is an increasingly well-recognized aspect of antiphospholipid syndrome. The most characteristic histopathology is that of thrombotic microangiopathy, and thrombosis occurring in the renal vasculature is thought to be the initiating event. Other less common pathologies have been reported, and the mechanisms of these are unclear. Therapy has been largely empiric. We report a case of NAPS in a patient with atypical pathology, who has declined therapy with immunosuppressive agents and anticoagulants and who has maintained normal renal function in 20 years of follow-up.

The effect of simvastatin on triglyceride-rich lipoproteins in patients with type 2 diabetic dyslipidemia: a SILHOUETTE trial sub-study.

OBJECTIVE: To determine if simvastatin effectively decreases the elevated levels of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which are characteristic of diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: We conducted a prespecified analysis from a double-blind, placebo-controlled, randomized, 6-week crossover trial in patients with type 2 diabetes and low HDL-C (< 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3 periods. We used the validated vertical auto profile (VAP) method to directly assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%) (n = 151) with stable type 2 diabetes (HbA1C < 9%), LDL-C > 100 mg/dL, HDL-C < 40 mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL). MAIN OUTCOME MEASURES: Percentage change from baseline in IDL and VLDL (TG-rich lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6-week treatment interval; percentage of patients who reached NCEP ATP III non-HDL goal of < 130 mg/dL by the end of each 6-week period. RESULTS: Both simvastatin 80 mg and 40 mg significantly reduced VLDL-C, VLDL3, and IDL, as well as the four LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg, compared with simvastatin 40 mg, provided additional efficacy. With simvastatin 80 mg, 77.2% of patients not at their non-HDL-C goal of < 130 mg/dL at study baseline reached goal, compared with 65.7% following simvastatin 40 mg treatment, and 2.2% following placebo. CONCLUSIONS: Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. A large percentage of these patients attained the NCEP ATP III non-HDL-C goal of < 130 mg/dL, which demonstrates the improvement of the atherogenic profile in these patients.

Shunt nephritis from Propionibacterium acnes in a solitary kidney.

Since its initial description in 1965, immune complex glomerulonephritis associated with ventriculoatrial shunts (VAS) has been reported widely in the literature. The most common incriminating organism is Staphylococcus epidermidis, but less often, an organism generally regarded as nonpathogenic, such as Propionibacterium acnes, has been noted as the cause. Shunt infection usually occurs within a few months after placement or manipulation of the shunt, and shunt nephritis (SN) develops gradually over months to years after. Treatment involves mandatory removal of the shunt and antibiotics; prognosis is variable. We report a case of SN with P acnes that is unusual because of its occurrence in a solitary kidney 6 years after shunt placement, persistently negative blood cultures, and normal complement levels. Percutaneous biopsy of a solitary kidney should be considered if it is expected that the result may guide therapy of progressive renal failure.

Lactic acidosis associated with stavudine administration: a report of five cases.

Type "B" lactic acidosis has been described in patients receiving the nucleoside analogs zidovudine, didanosine, and fialuridine. Lactic acidosis has also been described in 4 patients receiving combination therapy with stavudine and lamivudine. We describe the development of chronic type "B" lactic acidosis in 3 patients receiving stavudine as a single agent and in 2 patients receiving combination therapy with stavudine and either lamivudine or delavirdine, a nonnucleoside analog. All patients presented with abdominal pain, vomiting, and hepatic steatosis. Other signs of mitochondrial toxicity included pancreatitis and myopathy (2 cases). The mean duration of stavudine therapy was 9.4 months, and the mean observed peak lactate level+/-SD was 10.3+/-5 mmol/L. After discontinuation of stavudine treatment, lactic acidosis improved in 4 patients after 4-60 weeks, and 1 patient died. Evaluations for other causes of lactic acidosis, including hypoxemia, malignancy, sepsis, and cardiogenic shock, were negative.

Rechallenge of patients who had discontinued alendronate therapy because of upper gastrointestinal symptoms.

BACKGROUND: There have been reports from physicians in clinical practice that up to 30% of patients taking bisphosphonate therapy develop upper gastrointestinal (UGI) symptoms, many or most of which they assume to be related to the drug. However, in several large placebo-controlled clinical trials of bisphosphonates, the incidence of UGI symptoms has been > or =30%, even among patients receiving placebo, perhaps reflecting a high background incidence of UGI events in osteoporotic patients. OBJECTIVE: To assess the relationship between alendronate treatment and UGI complaints in patients who had discontinued treatment with alendronate in clinical practice because of UGI symptoms, we compared the incidence of such events on rechallenge with alendronate or placebo. METHODS: This was a multicenter, double-blind trial in which postmenopausal women with osteoporosis who had previously discontinued alendronate therapy because of a UGI adverse experience were randomized to daily treatment with either alendronate 10 mg or matching placebo (1:1 ratio) for 8 weeks. The primary end point was the cumulative incidence of discontinuations due to any UGI adverse experience. Secondary end points were the incidence of any clinical adverse experiences and the percentage change from baseline in urinary N-telopeptide adjusted for urinary creatinine at week 8. RESULTS: A total of 172 women were included in the study. They were a mean of 20.9 years past menopause, ranging in age from 41 to 90 years (mean, 67.0 years); 90.7% were white. On rechallenge, 14.8% (13/88) of patients in the alendronate group and 16.7% (14/84) in the placebo group discontinued treatment because of UGI adverse experiences. CONCLUSION: The results of this study suggest that many UGI adverse experiences reported during therapy with alendronate may reflect a high background incidence of UGI complaints and an increased sensitivity to detection of such complaints, rather than a causal relationship to therapy.

Hyperfiltration in African-American patients with type 2 diabetes. Cross-sectional and longitudinal data.

OBJECTIVE: Hyperfiltration may play a role in the development of diabetic nephropathy. African-American patients with diabetes have more than a fourfold increase in end-stage renal disease. The purpose of this study is to evaluate the impact of hyperfiltration on renal function in African-American patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Renal function of 194 African-American patients with diagnosed type 2 diabetes from 1 month to 36 years was assessed by studies of isotopic glomerular filtration rate (GFR), serum creatinine, creatinine clearance, and 24-h urinary albumin excretion rates. Thirty-four patients with a duration of diagnosed type 2 diabetes from 1 month to 10 years were found to have hyperfiltration (GFR > or = 140 ml.min-1.1.73 m-2). Fifteen of these patients received longitudinal follow-up of renal function for as long as 15 years after the initial study. RESULTS: Hyperfiltration is present in 15 (36%) of 42 patients whose duration of diagnosed type 2 diabetes is < 1 year, and it persists for up to 10 years in 14-20% of patients with diagnosed type 2 diabetes. Patients with hyperfiltration are younger than their counterparts without hyperfiltration when matched for duration of diagnosed diabetes. When followed over time, those patients with hyperfiltration were not more likely to develop impaired renal function as measured by GFR or creatinine clearance. CONCLUSIONS: Hyperfiltration does not identify patients at risk for deterioration in renal function.

Successful treatment of cisplatin-induced hemolytic uremic syndrome with therapeutic plasma exchange.

Cisplatin is a known cause of hemolytic uremic syndrome (HUS). The acute, fulminant form of cisplatin-induced HUS is almost always fatal. We present a 67-year-old Hispanic woman who was treated with cisplatin for squamous cell carcinoma of the tongue. Three days after receiving the treatment, she presented with increasing fatigue, decreased urine output, and confusion. Physical examination was remarkable for tachycardia of 130 beats/min, peripheral edema, and mental obtundation. Laboratory investigations showed a white cell count of 5,500/microL, hemoglobin level of 9.6 g/dL, hematocrit of 29.6%, and platelet count of 13,000/microL. Schistocytes were present on peripheral smear. Screening for disseminated intravascular coagulation was negative. Serum chemistry values included blood urea nitrogen 111 mg/dL, creatinine 3.8 mg/dL, and lactate dehydrogenase (LDH) 927 IU. The patient underwent hemodialysis and therapeutic plasma exchange (TPE), using fresh frozen plasma (FFP). Dialysis was no longer required after the fifth day. TPE was performed daily until the platelet count normalized on the 13th day, after which intertreatment intervals were extended until normalization of LDH levels on the 50th day. We conclude that the normally fatal, fulminant form of cisplatin-induced HUS can be successfully treated with standard TPE, using FFP replacement.

Carboplatin-related hematuria and acute renal failure.

Cisplatin is a potent tubular toxin with a high incidence of nephrotoxicity. Carboplatin is considered less nephrotoxic but can still cause tubular injury and interstitial nephritis in patients who have been previously treated with cisplatin. The affected individuals usually have nonoliguric renal failure with a urine output of more than a liter per day. We present a 57-year-old white woman with no history of renal disease who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for stage IC ovarian carcinoma. One month later, she received chemotherapy with paclitaxel (Taxol) and carboplatin. On the following day, she developed frank hematuria and flank pain associated with a diminished urine output. Intravenous pyelogram (IVP) showed bilateral hydronephrosis with a total blockage of dye flow at the level of intraureteral lucencies consistent with bilateral blood clots. Her coagulation profile and uric acid was normal. Her acute renal failure (ARF) spontaneously resolved in the following 24 hours, with a brisk diuresis presumably due to clot lysis. The follow-up IVP showed a resolution of obstructive changes. A review of the literature shows a previous case in which high doses of carboplatin were implicated as the cause of hemorrhagic cystitis, presumably by toxicity to transitional epithelium of the bladder. We believe that the current case represents carboplatin-induced damage to the transitional epithelium in the renal pelvi and ureters causing gross hematuria and blood clots, resulting in bilateral ureteral obstruction and hydronephrosis.

Outcome-associated factors in pediatric patients treated with extracorporeal membrane oxygenator after cardiac surgery.

BACKGROUND: The use of the extracorporeal membrane oxygenator (ECMO) for postoperative cardiac patients has not resulted in the same high success rate as when ECMO is used for neonates with pulmonary hypertension or pulmonary failure. The reason for this is poorly understood. METHODS AND RESULTS: We analyzed retrospectively all pediatric patients placed on ECMO after surgery for a congenital heart lesion between 1981 and 1995 (n = 64). Patients had a two-ventricular repair (A) or pulmonary blood flow supplied by an aortopulmonary shunt (B) or by a cavopulmonary connection (C). Indication for ECMO was unsatisfactory hemodynamics due to (1) ventricular dysfunction, (2) pulmonary failure, (3) pulmonary hypertension, or (4) a combination or (5) for unclear reasons. Hospital survival was related to these and other factors. Overall hospital survival was 33%; 42% of group A patients survived to discharge, whereas only 25% and 17% survived in groups B and C, respectively. Survival was unrelated to the indication for ECMO but appeared to be lower when ECMO was initiated in the operating room or > 50 hours after surgery. Except for one patient with pneumonia, no patient survived who was on ECMO for > 208 hours. ECMO discontinuation in nonsurvivors was due to neurological (30%) or multiple complications (39%), the lack of return of cardiac function (12%), or other reasons (15%). CONCLUSIONS: This review suggests that the diagnosis of single ventricle, initiation of ECMO in the operating room or > 50 hours after surgery, and ECMO for > 208 hours are associated with patient nonsurvival. Noncardiac complications more frequently led to discontinuation of ECMO than did failure of the return of cardiac function.

Mechanical ventilation and arterial blood gas measurements 24 hours postextracorporeal life support for survivors of pediatric respiratory failure.

OBJECTIVE: To summarize our institutional experience concerning mechanical ventilation support and blood gas measurements in the 24-hr period following extracorporeal life support (ECLS) for pediatric acute respiratory failure. DESIGN: Descriptive study. SETTING: A tertiary pediatric referral center. PATIENTS: Children aged 1 month to 18 yrs treated with ECLS for acute respiratory failure at University of Michigan Hospitals from November 1982 to June 1993. All patients aged 1 month to 18 yrs who received ECLS for acute respiratory failure were included. Patients who received ECLS primarily for cardiac support or who had a diagnosis of congenital gastrointestinal malformation (i.e. congenital diaphragmatic hernia) were excluded. INTERVENTIONS: ECLS for severe pediatric respiratory failure. MEASUREMENTS AND MAIN RESULTS: Forty-nine children were treated at our center with ECLS for acute respiratory failure 36 (73%) survived. Ventilator settings immediately after decannulation from ECLS for survivors were as follows: FIO2 0.53 +/- 0.18 (SD); intermittent mandatory ventilation (IMV) 29.6 +/- 1.18 breaths/min, positive end-expiratory pressure 5.3 +/- 1.6 cm H2O, mean airway pressure 12.6 +/- 2.9 cm H2O, and peak inspiratory pressure 31.7 +/- 5.5 cm H2O. Arterial blood gas measurements at decannulation were PaO2 89.4 +/- 30.9 torr (11.9 +/- 4.1 kPa), PaCO2 43.7 +/- 9.7 torr (5.8 +/- 1.3 kPa), and pH 7.39 +/- 0.07. Twenty-four hours after decannulation, ventilator settings and arterial blood gas measurements were as follows: FIO2 0.42 +/- 0.14, IMV 27.4 +/- 13.5 breaths/min, positive end-expiratory pressure 5.2 +/- 1.6 cm H2O, mean airway pressure 12.0 +/- 3.4 cm H2O, peak inspiratory pressure 31.1 +/- 6.5 cm H2O, PaO2 77.0 +/- 16.9 torr (10.3 +/- 2.3 kPa), PaCO2 44.9 +/- 8.4 torr (6.0 +/- 1.1 kPa), and pH 7.40 +/- 0.07. Variables associated with oxygenation status (P[A-a]O2) and mean airway pressure (oxygenation index) improved during the immediate 24-hr period postbypass (p < .05). CONCLUSIONS: Successful decannulation from ECLS for > 24 hrs resulted in long-term survival in 97% (36/37) of children. Ventilator parameters and arterial blood gas measurements during the 24-hr period following bypass have been described for this population. Such conventional support may indicate safe levels of oxygen and mechanical ventilation pressures for the postbypass recovering lung.

Interaction of hypertension and diabetes on renal function in black NIDDM subjects.

We studied renal function of 194 black subjects with duration of diagnosed NIDDM from 1 month to 36 years to determine the interaction of hypertension and diabetes on nephropathy. Renal function was assessed by isotopic GFR and RPF studies, and serum creatinine. One hundred seventeen of the 194 subjects had 24-hour urinary albumin excretion (AER). AER > 300 mg/24 h correlated with longer duration of NIDDM, decrease in GFR and RPF, and rise in serum Cr, and all subjects were hypertensive. AER 30 to 300 mg/24 h also correlated with a longer duration of NIDDM and 80% had hypertension. When 194 subjects were grouped according to duration of NIDDM and the presence or absence of hypertension, subjects who remained normotensive had normal renal function. In hypertensive subjects a decrease in GFR occurred with duration of NIDDM > 1 year and decrease in RPF with duration of NIDDM > 5 years. In hypertensive subjects with NIDDM > 10 years, 36% had impaired renal function (GFR < 80 ml/min/1.73 m2 or serum creatinine > 1.4 mg/dl) and 75% had microalbuminuria or clinical proteinuria. Within this group, those subjects who developed hypertension after their diagnosis of diabetes were likely to have evidence of nephropathy as compared to those subjects whose hypertension was diagnosed prior to or simultaneous with their diabetes: 17 of 20 (85%) versus 7 of 13 (54%), respectively (P = 0.05). These data provide insight into the relationship between hypertension and diabetes in the development of nephropathy in black NIDDM individuals.

Continuous versus intermittent nebulized terbutaline: plasma levels and effects.

The purpose of this investigation was to compare continuous versus intermittent nebulization of a beta 2-agonist, terbutaline, to determine whether differences exist in plasma concentrations or adverse cardiovascular effects of the drug with these two techniques for its administration. Sixteen children 6 to 16 yr of age, admitted for acute asthma, were enrolled in this randomized double-blind clinical trial. Nebulization of 16 mg of terbutaline over an 8-h period was performed either continuously or intermittently, with a dose of 4 mg given over 20 min every 2 h. The peak plasma terbutaline concentration for the intermittent nebulization treatment (INT) group (5.1 +/- 2.1 ng/ml) occurred 1 h after the fourth inhalation treatment and was similar to the peak concentration for the continuous nebulization treatment (CNT) group, which was reached at the end of the 8 h period (4.7 +/- 2.3 ng/ml). The maximum heart rate increase for the INT group (19.6 +/- 18.3 bpm) occurred 1 h after the fourth dose and was similar to the peak observed in the CNT group (19.6 +/- 19.2 bpm), which occurred after 3 h. Similar increases in systolic and decreases in diastolic pressures were observed for the INT and CNT groups. No evidence of serious adverse myocardial complications was seen in either group, as evidenced by measurements of the MB fraction of creatine phosphokinase (CPK-MB) and Holter-monitor recordings. Continuous nebulization of the terbutaline produces similar plasma concentrations and cardiovascular physiologic responses as intermittent nebulization.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic otitis media requiring ventilation tubes in tracheotomized ventilator dependent children.

The occurrence of sinusitis and middle ear effusions has frequently been attributed to the obstruction of the sinus ostia and/or eustachian tube. In the intensive care unit setting, edema caused by the irritation from nasogastric, nasotracheal and orotracheal tubes has been associated with this pathology and has been responsible for occult sepsis in this population. Our investigation was performed to determine the risk of chronic otitis media with effusion necessitating myringotomy with tympanostomy tubes among tracheotomized, ventilator dependent children in a consecutive series of children admitted to our recently created stable ventilator unit. We retrospectively reviewed the medical records of all tracheotomized, chronically ventilator dependent children < 48 months of age who had been hospitalized in this unit from the initial opening in September 1990 to January 1993. Data collected consisted of patient demographics, gestational age, cognitive abilities, age at onset of mechanical ventilation, age at tracheostomy, age at myringotomy, presence of nasogastric and gastroenterostomy tubes and evidence of gastric-esophageal reflux. All children underwent a tracheostomy procedure subsequent to the onset of mechanical ventilation. Of these patients, 9/12 (75%) later required myringotomy with tympanostomy tube placement following the occurrence of chronic otitis media with effusion. Ventilation tubes for chronic otitis media with effusion were not required in 3 patients. Using a case control study design, we examined the need of myringotomy tubes for children requiring continuous mechanical ventilation versus those requiring night-time only ventilation. The risk of myringotomy tubes in the continuously ventilated group (9/9) was significantly greater than the risk in the intermittently ventilated group (0/3) P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Simulated pediatric cardiopulmonary resuscitation: initial events and response times of a hospital arrest team.

BACKGROUND: Cardiopulmonary resuscitation (CPR) training programs exist to enhance knowledge and skills retention. However, they do not ensure that effective CPR will be performed by trainees or resuscitation teams. One aspect of CPR effectiveness is the ability of the team to respond to an emergency call in a timely manner. METHODS: We prospectively evaluated the time required for team members to respond to an emergency call and to initiate definitive treatment in our pediatric facility. The medical staff who responded had no prior knowledge of the simulated cardiac arrest (SCA) events. All events were recorded on audio-cassette tape to determine the sequence of events and response time of arrest team members. SCA scenarios represented examples of cardiac, hematologic, renal, respiratory, and pharmacologic pathophysiology. All participants were instructed to respond as though the SCA were an actual emergency. RESULTS: From December 1991 to January 1993, 37 SCAs were evaluated. Documentation began after a concise arrest scenario had been presented to a designated nursing representative who was to be the first rescuer on the scene. The rescuer first assessed the patient's condition, activated the cardiac arrest system (median elapsed time, MET, 0.50 minutes), and then initiated single-person CPR (MET 0.58 minutes). Administration of oxygen occurred at an MET of 2.25 minutes. The first member of the arrest team to respond was the pediatric resident (MET 3.17 minutes) followed by the respiratory therapist (MET 3.20 minutes), an ICU nurse (MET 3.58 minutes), a pharmacist (MET 3.42 minutes), and anesthesiology personnel (MET 4.70 minutes). DISCUSSION: The use of SCAs (termed "Mega Code") serves as an extension of Basic Life Support and Advanced Cardiac Life Support education and provides a valuable learning experience and quality assurance tool. Limitations that might influence patient outcome during an actual in-hospital arrest have led to refinements in our cardiac arrest procedures. Of particular note was the delay in oxygen administration, which may be linked to its omission from the 1986 and 1992 American Heart Association Basic Life Support Guidelines. CONCLUSION: We believe that BLS education for hospital employees should include and emphasize oxygen delivery for resuscitation.

Extracorporeal life support for severe pediatric respiratory failure: an updated experience 1991-1993.

OBJECTIVE: The purpose of this study was to examine our recent experience with children who had acute respiratory failure managed with extracorporeal life support (ECLS) from 1991 to 1993, to determine whether a change in survival rate had occurred in comparison with our previous experience. DESIGN: Historic and prospective cohort study. SETTING: A tertiary pediatric referral center. PATIENTS: All non-neonatal pediatric patients treated with ECLS for severe, life-threatening respiratory failure were examined. Overall, 25 patients have been managed with this life-support technique in the past 28 months. Eighty-four percent (21/25) were transferred to our medical center because of failure of conventional mechanical ventilation therapy. Descriptive data of the recent cohort were as follows (mean +/- SD): age 60 +/- 75 months, weight 23.6 +/- 24.8 kg, and male gender 44%. Duration of intubation before ECLS was 5.8 +/- 2.7 days. Arterial blood gas values and ventilator settings immediately before ECLS were as follows: fraction of inspired oxygen, 0.98 +/- 0.08; mean airway pressure, 21.6 +/- 6.2 cm H2O; peak inspiratory pressure, 45.5 +/- 9.6 cm H2O; positive end-expiratory pressure, 11.0 +/- 4.3 cm H2O; partial pressure of oxygen (arterial), 56 +/- 20 mm Hg (7.4 +/- 2.7 kilopascals); partial pressure of carbon dioxide (arterial), 46 +/- 17 mm Hg (6.1 +/- 2.3 kPa); and estimated alveolar-arterial oxygen tension difference, 572 +/- 81 mm Hg (76.3 +/- 10.8 kPa). Mean duration of ECLS was 373 +/- 259 hours. Of 25 recently treated patients, 22 (88%) survived their life-threatening respiratory illness to be discharged home; this represented a statistically improved survival rate in comparison with the 58% survival rate previously reported by us for similar patients (p < 0.05). Comparisons of arterial blood gas and mechanical ventilation-related variables measured 24 hours before and again immediately before bypass were similar in the two cohorts with the exception of higher mean partial pressure of carbon dioxide (arterial) 24 hours before bypass in the recent treatment group. For our entire experience, younger age groups had greater survival rates; 100% of infants less than 1 year of age survived. CONCLUSIONS: Treatment with ECLS is an evolving pulmonary rescue therapy with an 88% survival rate in our recent experience. The survival rate has improved to levels that may not greatly improve in the near future, especially for patients less than 1 year of age. Better patient selection or improved management strategies or both may be responsible for the improved patient outcome.

Alveolar-arterial oxygen gradients before extracorporeal life support for severe pediatric respiratory failure: improved outcome for extracorporeal life support-managed patients?

OBJECTIVE: Recent reports have described the usefulness of the alveolar-arterial oxygen tension difference (P[A-a]O2) in predicting mortality in children with acute respiratory failure managed with mechanical ventilation. We reviewed our experience with extracorporeal life support for acute pediatric respiratory failure and specifically examined P(A-a)O2 measurements during the 24 hrs before extracorporeal life support to determine if defined cutoffs established with conventional mechanical ventilation were applicable to extracorporeal life-support survival. DESIGN: Retrospective, case-series chart review. SETTING: A university tertiary medical center. PATIENTS: Infants and children (n = 36), one month to 18 yrs of age, with severe life-threatening respiratory failure who were believed to have failed conventional mechanical ventilatory support. INTERVENTIONS: Veno-venous or veno-arterial extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: From 1982 to 1992, we managed 36 pediatric patients with severe respiratory failure using extracorporeal life support. We identified 28 patients who had P(A-a)O2 values of > 400 torr (> 53.3 kPa) for the 24-hr time period before placement on bypass. At the time of bypass initiation, all blood gas and mechanical ventilator parameters except PaCO2 showed trends of worsening pulmonary function, compared with measurements done 24 hrs before bypass initiation. Oxygenation-related variables showed statistically significant worsening trends when measured 24 hrs before bypass, compared with the time of bypass: P(A-a)O2 539 vs. 582 torr (71.9 vs. 77.6 kPa), p < .01; PaO2/FIO2 ratio 70 vs. 57 torr (9.3 vs. 7.6 kPa), p < .05; oxygenation index 32 vs. 47 cm H2O/torr, p < .01; and FIO2 0.94 vs. 0.98, p < .05. Sixty-one percent of extracorporeal life support-managed patients (17 of 28) survived their life-threatening respiratory illness to be discharged home. CONCLUSIONS: Based on previous reports of the utility of P(A-a)O2 measurements to predict mortality, our preliminary evidence suggests that extracorporeal life support results in 62% survival for pediatric respiratory failure patients predicted to have no chance of survival using conventional mechanical ventilation. Prospective, randomized trials of children with severe acute respiratory failure managed with mechanical ventilation vs. extracorporeal life support may be indicated.

Influence of tidal volume, respiratory rate, and supplemental oxygen flow on delivered oxygen fraction using a mouth to mask ventilation device.

We examined the influence of the following parameters in determining the FiO2 delivered to a pediatric lung model using the mouth-to-mask method of resuscitation: rate of ventilation, inspiratory tidal volumes, and supplemental oxygen flow. With a ventilator rate of 20/min and tidal volumes (Vt) < or = 100 mL, an FiO2 of approximately .50 was observed with a supplemental oxygen flow of 5 L/min. Increasing the supplemental oxygen flow to 15 L/m did not appreciably increase the FiO2 (FiO2 = .53 versus FiO2 = .60, respectively), but did cause a significant and unintended increase in Vt. Similar results were noted with a ventilator rate of 12/min and Vt < or = 100 mL (FiO2 = .68 versus FiO2 = .73, respectively). We also observed a potentially hazardous situation involving the positioning of the supplemental oxygen port that might result in high inspiratory pressures (stacking of breaths) to the pediatric patient. We believe additional testing is warranted prior to widespread use of this device in children.

Extracorporeal life support for pediatric respiratory failure: predictors of survival from 220 patients.

OBJECTIVE: The purpose of this report was to examine the Extracorporeal Life Support Organization registry database for predictors of outcome for severe pediatric respiratory failure managed with extracorporeal life support. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization data registry. PATIENTS: All nonneonatal pediatric patients who were treated in the United States with extracorporeal life support for severe pediatric respiratory failure reported to the Extracorporeal Life Support Organization registry as of August 1991. Patients with congenital heart disease and congenital gastrointestinal malformations were excluded from study. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support for severe life-threatening pulmonary failures. MEASUREMENTS AND MAIN RESULTS: As of August 1991, 220 pediatric patients meeting study entry criteria were reported to the Registry having received extracorporeal life support for severe pulmonary failure, since 1982. Forty-six percent (102 of 220 patients) were successfully managed with this technology and survived to hospital discharge. The mean patient age was 36.8 +/- 51.6 months. Fifty-one percent of the patients were male. The mean duration of mechanical ventilation before extracorporeal life support was 6.3 +/- 5.9 days. Mean blood gas and ventilatory measurements obtained before extracorporeal life support were as follows: PaCO2 52 +/- 23 torr (6.9 +/- 3.0 kPa); PaO2 59 +/- 32 torr (7.8 +/- 4.3 kPa); estimated alveolar-arterial oxygen gradient 561 +/- 63.4 torr (74.8 +/- 8.5 kPa); peak airway pressure 49.5 +/- 13.1 cm H2O; mean airway pressure 24.3 +/- 8.2 cm H2O; positive end-expiratory pressure 11.8 +/- 6.3 cm H2O; ventilator rate 58 +/- 64.4 breaths/min; and FIO2 0.98 +/- 0.07. The mean duration of extracorporeal life support for all patients was 247 +/- 164 hrs. For the 102 survivors, the mean time for decannulation from extracorporeal life support to extubation from mechanical ventilation was 6.5 +/- 7.6 days. Stepwise multivariate logistic regression modeling found the following variables to be associated with patient survival: a) patient age, b) days of mechanical ventilation before extracorporeal life support, c) peak inspiratory pressure, d) alveolar-arterial oxygen gradient, and e) extracorporeal life support administered since December 31, 1988 (all p < .05). CONCLUSIONS: Extracorporeal life support may represent an effective rescue therapy for some selected pediatric patients with severe respiratory failure for whom conventional mechanical ventilation support has failed to improve. Predictors of survival for this life-support therapy exist that may be helpful for individual patient prognostication and future prospective study.

Predictors of outcome of severe respiratory syncytial virus-associated respiratory failure treated with extracorporeal membrane oxygenation.

OBJECTIVE: To examine the Extracorporeal Life Support Organization registry data base for all infants and children with respiratory syncytial virus-associated respiratory failure managed with extracorporeal life support, to delineate predictors of outcome. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization data registry. PATIENTS: All pediatric patients treated in the United States with extracorporeal life support for severe pediatric respiratory syncytial virus-associated respiratory failure reported to the registry, from 1982 through June 1992. INTERVENTIONS: Venoarterial or venovenous extracorporeal life support. MEASUREMENTS AND MAIN RESULTS: As of June 1992, fifty-three pediatric patients meeting study entry criteria were reported to the Pediatric Respiratory Failure Registry (n = 412) as having received extracorporeal membrane oxygenation (ECMO) for severe respiratory syncytial virus infection with pulmonary failure. Forty-nine percent (26/53) were successfully managed and survived to hospital discharge. The mean patient age was 5.0 +/- 8.6 months. Duration of mechanical ventilation before institution of extracorporeal life support was 8.1 +/- 6.2 days. Multivariate logistic regression analysis found four variables to be associated with patient nonsurvival at the p < 0.05 level: male gender, longer duration of mechanical ventilation before ECMO, higher peak inspiratory pressure, and lower ratio of arterial oxygen tension to fraction of inspired oxygen. Era of treatment was not associated with outcome. Receiver operator characteristic curve analysis of this multivariate model resulted in cutoff points of r = 0.5 and 0.1 that resulted in 92% sensitivity and 81% specificity (false-positive ratio 19%) and 96% sensitivity and 73% specificity (false-positive ratio 27%), respectively. CONCLUSIONS: Predictors of outcome of severe respiratory failure caused by respiratory syncytial virus infection managed with ECMO exist, and multivariate predictive models with high sensitivity and low false-positive risk are possible. Similar mathematical models may be helpful in establishing criteria for future trials of ECMO versus conventional respiratory support.