Pediatric Critical Care Studies Research Articles

Gender Disparity in Leading Authorship of Critical Care Clinical Trials: A Systematic Review and Meta-Analysis.

In critical care medicine, research trials serve as crucial avenues for disseminating knowledge, influencing clinical practices, and fostering innovation. Notably, a significant gender imbalance exists within this field, potentially mirrored in the authorship of critical care research. This study aimed to investigate an exploration to ascertain the presence and extent of female representation in first and senior authorship roles within critical care literature. To this end, a systematic search was conducted across PubMed, Google Scholar, and Web of Science databases for original articles published up to February 2024, coupled with a methodological quality assessment via the Newcastle-Ottawa Scale (NOS) and statistical analyses through Review Manager software (RevMan, version 5.4.1, The Cochrane Collaboration, 2020). The study's findings, distilled from seven studies included in the final analysis, reveal a pronounced gender disparity. Specifically, in critical care literature examining mixed populations, female first authors were significantly less common than their male counterparts, with an odds ratio (OR) of 4.25 (95% confidence interval (CI): 3.18-5.68; p < 0.00001). Conversely, pediatric critical care studies did not show a significant difference in gender distribution among first authors (OR: 1.37; 95% CI: 0.31-6.10; p = 0.68). The investigation also highlighted a stark underrepresentation of female senior authors in critical care research across both mixed (OR: 11.67; 95% CI: 7.76-17.56; p < 0.00001) and pediatric populations (OR: 5.41; 95% CI: 1.88-15.56; p = 0.002). These findings underscore the persistent underrepresentation of women in critical care literature authorship and their slow progression into leadership roles, as evidenced by the disproportionately low number of female senior authors.

Comparing the Quality of Domain-Specific Versus General Language Models for Artificial Intelligence-Generated Differential Diagnoses in PICU Patients.

Generative language models (LMs) are being evaluated in a variety of tasks in healthcare, but pediatric critical care studies are scant. Our objective was to evaluate the utility of generative LMs in the pediatric critical care setting and to determine whether domain-adapted LMs can outperform much larger general-domain LMs in generating a differential diagnosis from the admission notes of PICU patients. Single-center retrospective cohort study. Quaternary 40-bed PICU. Notes from all patients admitted to the PICU between January 2012 and April 2023 were used for model development. One hundred thirty randomly selected admission notes were used for evaluation. None. Five experts in critical care used a 5-point Likert scale to independently evaluate the overall quality of differential diagnoses: 1) written by the clinician in the original notes, 2) generated by two general LMs (BioGPT-Large and LLaMa-65B), and 3) generated by two fine-tuned models (fine-tuned BioGPT-Large and fine-tuned LLaMa-7B). Differences among differential diagnoses were compared using mixed methods regression models. We used 1,916,538 notes from 32,454 unique patients for model development and validation. The mean quality scores of the differential diagnoses generated by the clinicians and fine-tuned LLaMa-7B, the best-performing LM, were 3.43 and 2.88, respectively (absolute difference 0.54 units [95% CI, 0.37-0.72], p < 0.001). Fine-tuned LLaMa-7B performed better than LLaMa-65B (absolute difference 0.23 unit [95% CI, 0.06-0.41], p = 0.009) and BioGPT-Large (absolute difference 0.86 unit [95% CI, 0.69-1.0], p < 0.001). The differential diagnosis generated by clinicians and fine-tuned LLaMa-7B were ranked as the highest quality in 144 (55%) and 74 cases (29%), respectively. A smaller LM fine-tuned using notes of PICU patients outperformed much larger models trained on general-domain data. Currently, LMs remain inferior but may serve as an adjunct to human clinicians in real-world tasks using real-world data.

Editor's Choice Articles for March.

Welcome to March 2023 at Pediatric Critical Care Medicine (PCCM). There are three Editor’s Choices articles that each question established opinions and make us delve deeper into the relevant issues and potential implications for practice. The PCCM Connections for Readers focuses on biological mechanism–as a plea to our investigators and research authors, we do need to see more of this type of work at PCCM. WHAT ABOUT CORTICOSTEROIDS IN SEPSIS AND SEPTIC SHOCK? Klowak JA, Bijelic V, Barrowman N, et al; Genomics of Pediatric Septic Shock Investigators: The Association of Corticosteroids and Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II Biomarker Risk (1). Are we any closer to solving the question of using corticosteroid therapy in children presenting with septic shock? In this retrospective study of almost 500 children separated into two categories using the PERSEVERE-II biomarker score, the authors tested whether there was an interaction between grouping, corticosteroid use, and outcome. Our editorial sets this information in a historical context, from 2009 to 2021 (2), and makes us think about precision medicine, endotypes, and the contemporary randomized controlled trial (RCT). This new article and editorial follow a theme in PCCM discussed in the September 2022 issue (3), and readers should review the authors’ other relevant work about the difficulty of RCTs in the septic shock population (4,5). WHAT ABOUT THE COMPLEXITY OF FACTORS CONTRIBUTING TO OUTCOMES AFTER CARDIAC SURGERY? Brown KL, Moinuddin M, Jones A, et al: The Relationship Between Postoperative Complications and Children’s Quality of Life: A Mediation Analysis to Explore the Role of Family Factors (6). In this multicenter research from the United Kingdom, the authors identified a cardiac postoperative group with multiple morbidities and sought to identify a causal mediation analysis of parental health-related quality of life at 6 weeks after cardiac surgery, and their child’s quality of life at 6 months. Over 400 children contributed to the primary outcome and these new data add insight into the complexity of outcomes and the potential scope of psychological interventions to support parents of children who experience perioperative morbidities. Add this reading to the authors’ recent report on postoperative morbidities and neurodevelopment (7), and we are now building a more complete picture of how best to study late outcomes after critical illness (8,9). WHAT ABOUT THE MEASUREMENT OF CEREBRAL NEAR-INFRARED SPECTROSCOPY IN PEDIATRIC CARDIAC PATIENTS? Iliopoulis I, Cooper DS, Reagor JA, et al: Absolute Versus Relative Near-Infrared Spectroscopy in Pediatric Cardiac Patients (10). My third highlighted article is an analysis of near-infrared spectroscopy (NIRS) data: the devices and the validity of the measurements that we use during clinical care (10). Please read the report and even though it’s not what we thought or taught, our editorial writers argue that NIRS monitoring in patients with complex congenital heart disease is here to stay (11). Also, go back to a little-known Letter to the Editor in the January 2006 issue of PCCM with its powerful insights. In the letter, Britton Chance (1913–2010), the American founder of biomedical photonics and National Medal of Science winner in 1974, wrote to PCCM on the topic of quantification of brain oxygenation in humans in vivo (12). “PCCM CONNECTIONS” FOR READERS This month there are two other areas of research that pick up on our previous themes. They are of particular interest because they address mechanism, and we need to understand clinical biology if we are to make progress in our field. The first topic is the endothelial glycocalyx. We have previously published a definitive review about the endothelial glycocalyx as a fundamental determinant of vascular permeability in sepsis (13), and a clinical research observation of glycocalyx degradation products contributing to metabolic acidosis following cardiopulmonary bypass (14). In a single-center research study from Colombia, the authors (same ones that wrote the previous PCCM definitive review) look at the time course of glycocalyx degradation in children with sepsis following a bolus of intravenous fluids (15). The article comes with an editorial (16). The second topic is the morbidity of hyperoxia. In early 2022 we learned that there are 16 pediatric critical care studies with over 27 thousand patients that, collectively, suggests an association between hyperoxia and greater odds of mortality (17). We now have a mechanistic substudy nested within the pilot feasibility RCT of liberal versus conservative oxygenation targeting (i.e., pulse oximetry > 94% versus 88%−92%, respectively) (18). The authors report redox responses and gene expression of hypoxia-inducible factor 1a in the two oxygenation groups. Hopefully, their hypothesis will be tested in the now completed RCT of oxygen targeting and outcome in pediatrics (19). Finally, another highlight for me is a narrative essay entitled “The Trip of a Lifetime” (20).

Vitamin D Deficiency in Pediatric Critical Care.

Vitamin D deficiency (VDD) is a well-established cause of pediatric bone and muscle disease. In addition, a role has been recognized for vitamin D in the health and stress response of other organs, including the cardiovascular, immune, and respiratory systems. As these organs are central to the development of and recovery from critical illness, VDD has been hypothesized to be a modifiable risk factor for ICU outcome. Over the past 5 years, a growing number of adult and pediatric critical care studies have investigated the prevalence of VDD and its association with illness severity and outcome. The adult studies have recently been synthesized in systematic reviews, with results that convincingly suggest the need for trials to determine whether optimization of vitamin D status improves outcome. In contrast, the pediatric ICU and related literature has not been similarly synthesized. The goal of this review is to describe vitamin D metabolism, known biological mechanisms, potential role in pathophysiology, and summarize the available pediatric intensive care unit (PICU) studies reporting on prevalence of VDD deficiency and its association with outcome. The problems with currently approved supplementation approaches and alternative strategies are discussed, including evidence from available RCTs in adult ICU. Altogether the results suggest that critically ill children are at risk for VDD, and that VDD appears to be associated with a worse clinical course. Clinical trials evaluating novel approaches to testing for and supplementing vitamin D require exploration.

1,25-Dihydroxyvitamin D Levels in Pediatric Intensive Care Units: Risk Factors and Association With Clinical Course

Multiple adult and some pediatric critical care studies have suggested that poor vitamin D status is associated with illness severity and outcome. The majority have evaluated vitamin D status through serum 25-hydroxyvitamin D [25(OH)D]. Critical illness-related organ dysfunction may result in impaired conversion of 25(OH)D to the active hormone 1,25-dihydroxyvitamin D [1,25(OH)2D]. Consequently 1,25(OH)2D levels could be an independent additive prognostic marker in the intensive care unit. The distribution of 1,25(OH)2D levels, prevalence of low levels, investigation of risk factors, and tests for associations with markers of illness severity and outcome are reported. This was a secondary analysis of data and samples collected as part of a prospective cohort study in six Canadian pediatric intensive care units (PICUs). Admission blood 1,25(OH)2D concentrations were measured. The median cohort 1,25(OH)2D level was 93.3 pmol/L (interquartile range, 53.0-121.9) with 13% (95% confidence interval, 9-17) and 21% (95% confidence interval, 17-27) of patients having levels of <40 and <50 pmol/L, respectively. Low 1,25(OH)2D levels occurred more often in patients with low 25(OH)D and hepatic, renal, and parathyroid organ dysfunction. After adjustment for 25(OH)D, low 1,25(OH)2D levels were not associated with catecholamine or fluid administration, ventilation, PICU length of stay, or mortality. Critically ill children are at risk for low 1,25(OH)2D levels, particularly in the presence of established risk factors. However, the lack of association between the 1,25(OH)2D level and selected outcome measures, after controlling for 25(OH)D, does not suggest value in measuring this metabolite at the time of PICU admission.

Health-related quality of life following pediatric critical illness

The aims of this focused review of the literature on children surviving critical illness were to (1) determine whether health-related quality of life (HRQL) represents a clinically meaningful outcome measure for children surviving critical illness and (2) evaluate the HRQL measures implemented in pediatric critical care studies to date. This was a focused review of the literature from 1980 to 2015 based on a search of EMBASE/PubMed, MEDLINE and PsycInfo assessing trends and determinants of HRQL outcomes in children surviving critical illness. We also evaluated the psychometric properties of the HRQL instruments used in the studies identified by examining each measure's reported reliability, validity and sensitivity to clinical change. The literature search identified 253 pediatric articles for potential inclusion in the review, among which data from 78 studies were ultimately selected for inclusion. Of the 22 measures utilized in the studies reviewed, only four demonstrated excellent psychometric properties for use in pediatric critical care trials. Trends in HRQL identified in the studies reviewed suggest significant ongoing morbidity for children surviving critical illness. Key determinants of poor HRQL outcomes include reason for PICU admission (sepsis, meningoencephalitis, trauma), antecedents (chronic comorbid conditions), treatments received (prolonged cardiopulmonary resuscitation, long-stay patients, invasive technology), psychological outcomes (post-traumatic stress disorder, parent anxiety/depression) and social and environmental characteristics (low socioeconomic status, parental education and functioning). Validated pediatric HRQL instruments are now available. Significant impact on HRQL has been demonstrated in acute and acute on chronic critical illness. Future pediatric critical care interventional trials should include both mortality as well as long-term HRQL measurements to truly ascertain the full impact of critical illness in children.

Relationship between the functional status scale and the pediatric overall performance category and pediatric cerebral performance category scales.

Functional status assessment methods are important as outcome measures for pediatric critical care studies. To investigate the relationships between the 2 functional status assessment methods appropriate for large-sample studies, the Functional Status Scale (FSS) and the Pediatric Overall Performance Category and Pediatric Cerebral Performance Category (POPC/PCPC) scales. Prospective cohort study with random patient selection at 7 sites and 8 children's hospitals with general/medical and cardiac/cardiovascular pediatric intensive care units (PICUs) in the Collaborative Pediatric Critical Care Research Network. Participants included all PICU patients younger than 18 years. Functional Status Scale and POPC/PCPC scores determined at PICU admission (baseline) and PICU discharge. We investigated the association between the baseline and PICU discharge POPC/PCPC scores and the baseline and PICU discharge FSS scores, the dispersion of FSS scores within each of the POPC/PCPC ratings, and the relationship between the FSS neurologic components (FSS-CNS) and the PCPC. We included 5017 patients. We found a significant (P < .001) difference between FSS scores in each POPC or PCPC interval, with an FSS score increase with each worsening POPC/PCPC rating. The FSS scores for the good and mild disability POPC/PCPC ratings were similar and increased by 2 to 3 points for the POPC/PCPC change from mild to moderate disability, 5 to 6 points for moderate to severe disability, and 8 to 9 points for severe disability to vegetative state or coma. The dispersion of FSS scores within each POPC and PCPC rating was substantial and increased with worsening POPC and PCPC scores. We also found a significant (P < .001) difference between the FSS-CNS scores between each of the PCPC ratings with increases in the FSS-CNS score for each higher PCPC rating. The FSS and POPC/PCPC system are closely associated. Increases in FSS scores occur with each higher POPC and PCPC rating and with greater magnitudes of change as the dysfunction severity increases. However, the dispersion of the FSS scores indicated a lack of precision in the POPC/PCPC system when compared with the more objective and granular FSS. The relationship between the PCPC and the FSS-CNS paralleled the relationship between the FSS and POPC/PCPC system.

Factors affecting consent in pediatric critical care research

Consent for research is a difficult and unpredictable process in pediatric critical care populations. The objectives of this study were to describe consent rates in pediatric critical care research and their association with patient, legal guardian, consent process, and study design-related factors. A prospective, cohort study was conducted from 2009 to 2010 in six tertiary care pediatric intensive care units (PICU) in Canada with legal guardians of patients who were approached for consent for any ongoing PICU research study. Data were recorded on details of the consent process for all consent encounters. We recorded 271 consent encounters. The overall consent rate was 80.1% (217/271). We observed higher consent rates when the research assistant was introduced by a member of the clinical team prior to approaching the family (89.7 vs. 77.7%; P = 0.04). Legal guardians of cardiac surgery patients were less likely to provide consent than those of all other patients (75.3 vs. 86.0%; P = 0.03). There was no difference in consent rates between therapeutic (117/145, 80.7%) versus non-therapeutic studies (100/126, 79.4%; P = 0.88). This study provides future researchers with consent data for determination of recruitment rates, sample sizes, budget estimations, and study timelines. Future pediatric critical care studies should consider incorporating the lower consent rates in cardiac surgery patients and routine introduction of the research assistant to the family by a member of the patient's care team into their study designs. The potential influence of parental factors on consent rates in pediatric critical care studies requires further research.

Newer Inotropes in Pediatric Heart Failure

In the cardiac setting in pediatrics, inotropic support is often employed based on the extrapolation from adult studies, the underlying pathophysiology, pharmacodynamics of inotropes, and anecdotal experience. Large pediatric critical care studies involving inotropic support are rare. Levosimendan, a calcium-sensitizing agent with inotropic and lusitropic properties, is a pyridazole dinitrate derivative with linear pharmacokinetics and a relatively short half life, although an active metabolite, namely, OR-1876, has a half life of 70-80 hours accounting for a prolonged effect. Albeit few, pediatric studies involving levosimendan suggest similar pharmacokinetics to adults with heart failure, an efficacy at least equal to that of milrinone, favorable myocardial oxygen effects, and an ability to decrease concomitant catecholamine dosing. Levosimendan may be a promising new agent in pediatrics, but further experience and study are warranted. Finally, istaroxime, a calcium cycling agent that is in the beginning of adult study, may be another inotrope with lusitropic properties that might be applicable to pediatric patients.

Volume-outcome relationships in pediatric intensive care units.

Pediatric intensive care units (PICUs) have expanded nationally, yet few studies have examined the potential impact of regionalization and no study has demonstrated whether a relationship between patient volume and outcome exists in these units. Documentation of an inverse relationship between volume and outcome has important implications for regionalization of care. This study examines relationships between the volume of patients and other unit characteristics on patient outcomes in PICUs. Specifically, we investigate whether an increase in patient volume improves mortality risk and reduces length of stay. A prospective multicenter cohort design was used with 16 PICUs. All of the units participated in the Pediatric Critical Care Study Group. Participants. Data were collected on 11 106 consecutive admissions to the 16 units over a 12-month period beginning in January 1993. Risk-adjusted mortality and length of stay were examined in multivariate analyses. The multivariate models used the Pediatric Risk of Mortality score and other clinical measures as independent variables to risk-adjust for illness severity and case-mix differences. The average patient volume across the 16 PICUs was 863 with a standard deviation of 341. We found significant effects of patient volume on both risk-adjusted mortality and patient length of stay. A 100-patient increase in PICU volume decreased risk-adjusted mortality (adjusted odds ratio:.95; 95% confidence interval:.91-.99), and reduced length of stay (incident rate ratio:.98; 95% confidence interval:.975-.985). Other PICU characteristics, such as fellowship training program, university hospital affiliation, number of PICU beds, and children's hospital affiliation, had no effect on risk-adjusted mortality or patient length of stay. The volume of patients in PICUs is inversely related to risk-adjusted mortality and patient length of stay. A further understanding of this relationship is needed to develop effective regionalization and referral policies for critically ill children.

Relationship of illness severity and length of stay to functional outcomes in the pediatric intensive care unit: a multi-institutional study.

The purpose of this study was to establish relationships between illness severity, length of stay, and functional outcomes in the pediatric intensive care unit (PICU) by using multi-institutional data. We hypothesized that a positive relationship exists between functional outcome scores, severity of illness, and length of stay. The study used a prospective multicentered inception cohort design. The study was conducted in 16 PICUs across the United States that were member institutions of the Pediatric Critical Care Study Group of the Society of Critical Care Medicine. In total, 11,106 patients were assessed, representing all admissions to these intensive care units for 12 consecutive months. Functional outcomes were measured by the Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scales. Both scales were assessed at baseline and discharge from the PICU. Delta scores were formed by subtracting baseline scores from discharge scores. Other measurements included admission Pediatric Risk of Mortality scores, age, operative status, length of stay in the PICU, and diagnoses. Interrater reliability was assessed by using a set of ten standardized cases on two occasions 6 months apart. Baseline, discharge, and delta POPC and PCPC outcome scores were associated with length of stay in the PICU and with predicted risk of mortality (p < .01). Incorporation of baseline functional status in multivariate length of stay analyses improved measured fit. Mild baseline cerebral deficits in children were associated with 18% longer PICU stays after controlling for other patient and institutional characteristics. Moderate and severe baseline deficits for both the POPC and PCPC score predict increased length of stay of between 30% and 40%. On the standardized cases, interrater consensus was achieved on 82% of scores with agreement to within one neighboring class for 99.7% of scores. These data establish current relationships for the POPC and PCPC outcome scales based on multi-institutional data. The reported relationships can be used as reference values for evaluating clinical programs or for clinical outcomes research.

Differences in pediatric ICU mortality risk over time.

To compare pediatric intensive care unit (ICU) mortality risk using models from two distinct time periods; and to discuss the implications of changing mortality risk for severity systems and quality-of-care assessment. Consecutive admissions (n = 10,833) from 16 pediatric ICUs across the United States that participate in the Pediatric Critical Care Study Group were recorded prospectively. Data collection occurred during a 12-mo period beginning in January 1993. Data collection for the development and validation of the original Pediatric Risk of Mortality (PRISM) score occurred from 1980 to 1985. The original PRISM coefficients were used to calculate mortality probabilities in the current data set. Updated estimates of mortality probabilities were calculated, using coefficients from a logistic regression analysis using the original PRISM variable set. Quality-of-care tests were performed using standardized mortality ratios. Risk of mortality from pediatric ICU admission improved considerably between the two periods. Overall, the reduction in mortality risk averaged 15% (p < .001). Analysis of mortality risk by age indicated a large improvement for younger infants. The mortality risk for infants <1 mo improved by 39% (p < .001). Mortality risk improved by 28% (p < .001) for infants between 1 and 12 mos. Analysis of mortality risk by principal diagnosis indicated substantial improvement in respiratory diseases, including respiratory diseases developing in the perinatal period. The mortality risk for respiratory diseases improved by 45% (p < .001). The improvement in mortality risk substantially deteriorated the calibration of the original PRISM severity system (p < .001). As a result of changing mortality risk, the standardized mortality ratios across the 16 pediatric ICUs demonstrated substantial disparities, depending on the choice of models. This study documents differences in pediatric ICU risk of mortality over time that are consistent with a general improvement in the quality of pediatric intensive care. Despite continued widespread use of the original PRISM, recent improvements in pediatric ICU quality of care have negated its usefulness for many intended applications, including quality-of-care assessment.

Improved Outcome for Acute Hypoxemic Respiratory Failure in Children: Interim Results of a Prospective, Multi-institutional Study from the PARF Study Group † 185

The Pediatric Acute Respiratory Failure (PARF) Study Group was organized to study the effects of new therapies on the outcome of lung injury in children. Each center agreed to use similar pressure-limited ventilator strategies including high frequency ventilation (HFV) in all patients. Methods: All intubated children in participating centers with lung injury requiring at least 50% FiO2 and an end expiratory pressure greater than 5cm H2O were enrolled and data were prospectively collected. Patients with significant co-morbidities (chronic lung disease, immunocompromising conditions, cardiac disease, profound, acute central nervous system injury) were excluded from this analysis. Outcome was compared with a validated mortality prediction tool(Crit Care Med 24:323-9, 1996) using data from the Pediatric Critical Care Study Group multi-insitutional study in 1991 (Chest 108: 789-97, 1995) in which patients were selected using the same criteria. Results: In an interim analysis of 131 patients from 7 centers with complete data, 77 patients did not have co-morbidities. Mortality (18.2%) was significantly lower (P=.003) than predicted (32.8%). Improvement appeared in each mortality risk quartile. Severity of disease, as measured by oxygenation index (22 +/- 16) and PRISM score(14 +/- 8), was similar to values from the 1991 predictive data set. The highest peak airway pressure (33 +/- 6 cm H2O) and pCO2 (66 +/- 16 Torr) confirmed the use of pressure limited strategies. The use of high frequency ventilation (34%) was higher than in 1991, but improvement in mortality over predicted was noted in both patients treated with (P=.05) and without (P=.03) HFV. Conclusions: Survival following acute lung injury in patients without co-morbid conditions has improved since 1991 co-incident with the widespread use of pressure limited ventilator strategies.(Supported in part by Ronald MacDonald Charities).

Effectiveness of ribavirin in otherwise well infants with respiratory syncytial virus-associated respiratory failure

OBJECTIVE: To examine ribavirin's effectiveness in otherwise well infants with respiratory syncytial virus (RSV)–associated respiratory failure. DESIGN: Prospective multicenter cohort study. SETTING: Pediatric critical care units affiliated with the Pediatric Critical Care Study Group; 38 centers from the United States and Canada participated. PATIENTS: Infants with RSV-associated respiratory failure undergoing mechanical ventilation. INTERVENTIONS: NONE. MEASUREMENTS AND MAIN RESULTS: Data collected included demographic information; dates of hospitalization, intensive care, and mechanical ventilation; all patient diagnoses; reason for tracheal intubation; dates of ribavirin use before and during mechanical ventilation; time in hours after intubation until ribavirin administration; Pediatric Risk of Mortality (PRISM) score; and outcome. A total of 439 patients received mechanical ventilation for RSV-associated respiratory failure; 223 were classified as previously well and met entry criteria. Ninety-one infants (41%) received ribavirin during mechanical ventilation. The PRISM scores during the initial 24 hours of intensive care and blood gas measurements before intubation were similar for patients who received ribavirin versus those who did not. Use of ribavirin during mechanical ventilation was associated with prolonged duration of mechanical ventilation ( p <0.01) in a multivariate model that controlled for patient age, gender, prematurity status, and use of ribavirin before intubation. Subgroup analysis of mechanical ventilation days for previously well patients was 5.0 ± 4.2 in the no-ribavirin group versus 6.4 ± 5.0 in the ribavirin group ( p <0.05) and for well premature infants was 6.3 ± 4.9 in the no-ribavirin group versus 9.0 ± 6.3 in the ribavirin group ( p <0.01). The mortality rates for the term and the premature groups were similar for treated and untreated patients. CONCLUSIONS: Ribavirin administration during mechanical ventilation to previously well infants with RSV infection was not associated with reductions in either mortality rates or duration of mechanical ventilation. Additional clinical effectiveness studies are required to define specific groups in which the use of aerosolized ribavirin is indicated. (J P EDIATR 1996;128:422-8)

The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure

Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency in the treatment of acute respiratory failure in pediatric patients. Our objective in this study was to test the hypothesis that ECMO improves outcome in pediatric patients with acute respiratory failure. Multicenter, retrospective cohort analysis. Forty one pediatric intensive care units participated in the study under the auspices of the Pediatric Critical Care Study Group. All pediatric patients admitted to the participating institutions with acute respiratory failure during 1991 were included. Patients with congenital heart disease, contraindications to ECMO, or incomplete data were excluded, yielding a data set of 331 patients from 32 hospitals. Conventional mechanical ventilation, high-frequency ventilation, and extracorporeal membrane oxygenation. Multivariate logistic regression analysis was used to identify factors associated with survival. In a second analysis, pairs of ECMO and non-ECMO patients, matched by severity of disease and respiratory diagnosis, were compared. The use of ECMO (p = .0082), but not the use of high-frequency ventilation, was associated with a reduction in mortality. Other factors independently associated with mortality included oxygenation index (p < .0001), Pediatric Risk of Mortality score (PRISM) (p < .0001) and the Paco2 (p = .045). In 53 diagnosis- and risk-matched pairs, there was a significantly lower mortality rate (26.4% vs. 47.2%; p < .01) in the ECMO-treated patients. When all patients were stratified into mortality risk quartiles on the basis of oxygenation index and PRISM score, the proportion of deaths among ECMO-treated patients in the 50% to 75% mortality risk quartile was less than half the proportion in the non-ECMO treated patients (28.6% vs. 71.4% p < .05)> No effect was seen in the other quartiles. The use of ECMO was associated with an improved survival in pediatric patients with respiratory failure. The lack of association of outcome with treatment in the ECMO-capable hospital or with another tertiary technology (i.e. high-frequency ventilation) suggests that ECMO itself was responsible for the improved outcome. Further studies of this procedure are warranted but require broad-based multi-institutional participation to provide sufficient statistical power and sensitivity to demonstrate efficacy.

PREDICTION OF FUNCTIONAL OUTCOME IN PICU: A MULTI-INSTITUTIONAL STUDY.

Sandra Harshbarger, & the Pediatric Critical Care Study Group. University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Department of Pediatrics, 800 Marshall, Little Rock, AR 72202-3591.