Partial liquid ventilation for the prevention of mortality and morbidity in paediatric acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Acute lung injury, and acute respiratory distress syndrome, are syndromes of severe respiratory failure. Children with acute lung injury or acute respiratory syndrome have high mortality and significant morbidity. Partial liquid ventilation is proposed as a less injurious form of respiratory support for these children. Uncontrolled studies in adults have shown improvement in gas exchange and lung compliance with partial liquid ventilation A single uncontrolled study in six children with acute respiratory syndrome showed some improvement in gas exchange during three hours of partial liquid ventilation. OBJECTIVES: To assess whether partial liquid ventilation reduces either mortality or morbidity, or both, in children with acute lung injury or acute respiratory syndrome. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 2, 2003; MEDLINE (1966 to April 2003); and CINAHL (1982 to April 2003); intensive care journals and conference proceedings; reference lists and 'grey literature'. SELECTION CRITERIA: Randomized controlled trials which compared partial liquid ventilation with other forms of ventilation, in children (28 days - 18 years) with acute lung injury or acute respiratory syndrome, reporting one or more of the following: mortality; duration of mechanical ventilation, respiratory support, oxygen therapy, stay in the intensive care unit, or stay in hospital; infection; or long term cognitive impairment or neurodevelopmental progress or other long term morbidities. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated the quality of the relevant studies and extracted the data from the included studies. MAIN RESULTS: Only one study enrolling 182 patients (only reported as an abstract in conference proceedings) was identified and found eligible for inclusion: the authors report only limited results. The trial was stopped prematurely and therefore under-powered to detect any significant differences. The only outcome of clinical significance available was 28 day mortality: there was no statistically significant difference between groups with a relative risk for 28 day mortality in the partial liquid ventilation group of 1.54 (95% confidence intervals of 0.82 to 2.9). REVIEWERS' CONCLUSIONS: There is no evidence from randomized controlled trials to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory syndrome: adequately powered, high quality randomized controlled trials are still needed to assess its efficacy. Clinically relevant outcome measures should be assessed (mortality at discharge and later, duration of respiratory support and hospital stay, and long-term neurodevelopmental outcomes) and the studies should be published in full.

Quality assurance of paediatric cardiac surgery: a prospective 6-year analysis.

OBJECTIVE: To audit effective quality assurance methods to monitor outcomes following paediatric cardiac surgery at a single institution. METHODS: All patients undergoing cardiac surgery from January 1996 to December 2001 were enrolled prospectively. Patients were stratified by complexity of surgical procedure into four groups, with Category 4 being the most complex procedure. Outcome measures included death, length of admission and morbidity from complications. RESULTS: A total of 1815 patients underwent 1973 surgical procedures. Of these, 1447 (73.3%) were cardiopulmonary bypass procedures, and 543 (27.5%) were more complex (Category 3 and 4) procedures. Median patient age was 3.5 years (range, 1 day-20 years) and patient weight 15.0 kg (range, 900 g to 90 kg). Sixty-six patients (3.6%) died during the study period. Of the procedures in 1996, 22.7% were classified as complex compared with 29.2% of procedures in 2001. The annual surgical mortality ranged from 1.9-4.7% (P = 0.20), and when mortality was adjusted for complexity of surgery, there was no significant yearly variation in the mortality rate (P = 0.57). Analysis of individual surgeon's results showed no significant difference in the mortality rate by complexity of surgery performed (P = 0.90). Mean ventilation times did not change significantly over time (P = 0.79). The yearly incidence of significant neurological complications ranged from 0.6% to 4.5% and the incidence of arrhythmias from 4.2% to 8.0%. No difference was detected between the years. CONCLUSIONS: Stratifying complexity of surgery proved valuable in monitoring surgical outcomes and detecting differences in performance over time as large subgroups were created for analysis.

Renal developmental arrest in sudden infant death syndrome.

Investigations linking sudden infant death syndrome (SIDS) and type II intrauterine growth retardation (IUGR) have thus far failed due in part to technical limitations. Recently developed stereological methods for the unbiased estimation of total nephron number in the human kidney are capable of detecting deviations from normal values of greater than 10%. We compared the total number of nephrons in the kidneys of 24 SIDS victims with those from 16 controls with the same age range. Mean nephron number was significantly (P < 0.001) reduced in ex-IUGR SIDS cases (birthweight under the 10th centile, n = 9, mean number 635,000, range 327,000-1,010,000) in comparison with controls (903,000, 740,000-1,060,000). A similarly significant (P < 0.01) reduction in the "normal birthweight" SIDS group (birthweight over 10th centile, n = 15, 690,000, 361,000-1,040,000) was found. This hitherto unreported renal developmental arrest may be only one manifestation of a general, somatic developmental defect, reflecting adverse intrauterine conditions; other organ systems, similarly critical to homeostasis may be comparably affected. The findings, although not proposed as direct cause of SIDS, may represent a potential explanation for the recognized association of IUGR and SIDS, and provide--we believe--the first quantitative evidence of intrauterine growth retardation in, at least a number of, children of average birthweight.

"Medullary ray glomerular counting" as a method of assessment of human nephrogenesis.

Renal weight (left-right combined), as a parameter of renal development, is required to be less than half the normal value for age for a statistically confident diagnosis of hypoplasia. "Medullary ray glomerular counting" (MRGC), counting cortical glomerular generations, has been proposed as a simple technique of possibly greater sensitivity. Recent development of the Disector method for the unbiased stereological estimation of total glomerular number has provided a, hitherto unavailable, "golden standard" with which to determine the diagnostic potential of MRCG. Both "true" (actual number of generations seen) and "assumed" (a subjective "guess" of the total number of generations) MRGC counts were determined in 11 pairs of kidneys from spontaneously aborted, normally developed, non-malformed fetuses (gestational age: 15-40 weeks). Each kidney was randomly analysed blind and on two separate occasions by two paediatric pathologists using a written protocol. Results were compared with unbiased stereological estimates of glomerular number. Intra- and inter-observer and intra- and inter-(left-right)renal reproducibility were analysed. In conclusion, MRGC, using "real" counts, is a highly reproducible parameter of renal development from 15-36 weeks' gestation. Sensitivity for detection of both hypoplasia and maturation delay increase with gestational age and generally exceeds that of renal weight.

The effect of intrauterine growth retardation on the development of renal nephrons.

OBJECTIVE: To investigate the effect of Type II (asymmetrical) intrauterine growth retardation (IUGR) on renal development. DESIGN: A prospective descriptive study. SETTING: Department of Fetal and Infant Pathology, Liverpool Children's Hospital. SUBJECTS: Six (severely) affected IUGR stillbirths of known gestational age with a control group of stillbirths with birthweight greater than 10th centile, and eight liveborn IUGR infants who died within a year of birth with a control group of appropriately grown infants who died within a year of birth (postnatal groups). TECHNIQUES: The kidneys from all the groups studied were analysed using unbiased, reproducible and objective design-based stereological techniques. MAIN OUTCOME MEASURES: Total renal nephron (glomerular) numbers and average volumes of total nephron and cortical and medullary nephron segments. RESULTS: Nephron number estimates lay below the control group's 5% prediction limit in five out of the six growth-retarded stillbirths, and were significantly (P less than 0.005, IUGR at 65% of the control mean) reduced in the postnatal group. Estimates of nephron (segment) volume did not differ between control and IUGR groups. CONCLUSIONS: Type II intrauterine growth retardation may exert a profound effect on renal development. The reduced nephron number at birth, together with the lack of any early postnatal compensation in either nephron number or nephron size, emphasizes the need for vigorous antenatal surveillance for IUGR and consideration of elective preterm delivery of affected fetuses. A systematic review of other organs, which develop in a similarly rapid fashion during the late intrauterine period, is indicated by this work. With one exception, all birthweights in the growth-retarded groups were below the third centile, thus the precise quantitative relation between progressive IUGR and renal function requires further assessment.

Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle.

The disector method, a stereologic procedure unbiased by feature size, shape, or tissue-processing methods, for the estimation of total glomerular number was performed on pairs of human kidneys from 11 normal spontaneous second trimester abortions and stillbirths (15 to 40 weeks gestation). In addition, gestational age-dependent patterns of change in the average volume of the nephron and its cortical and medullary segments were analyzed. Mean glomerular number, plateauing at 36 weeks, increased from 15,000 at 15 weeks to 740,000 at 40 weeks. Average volume of the medullary nephron segment (Henle's loop) increased throughout pregnancy. Average volume of the cortical nephron segment (Tubuli Contorti) decreased from 15 weeks to 25 weeks, then increased after 36 weeks. Fractional volume of the renal cortex decreased from 15 weeks to 40 weeks. Three to 4 hours of microscopic analysis time were required per kidney on routinely processed 5-microns hematoxylin and eosin-stained paraffin sections. Average coefficient of error for number estimation was 8.02%. Average intra- and interobserver reproducibilities were 96.8 and 93.7%, respectively. The demonstrated temporal differences in the development of the cortical and medullary nephron components may result in a dissociation of function, which may explain the increased incidence of fetal hydrops in the second trimester of pregnancy, and which must be taken into account in the treatment of (very) premature infants. Although the number of kidneys included in this study is limited, as they reflect the whole period of antenatal development relevant to neonatal intensive care, the disector method of glomerular number estimation shows significant potential for the analysis and increased understanding of the development of renal function. The method appears to be more sensitive in detecting small and early deviations from normal renal growth and development than previously available parameters e.g., renal weight and (cortical) volume.