When a Child Dies in the PICU Despite Ongoing Life Support.

OBJECTIVES: To examine the circumstance of death in the PICU in the setting of ongoing curative or life-prolonging goals. DATA SOURCES: Multidisciplinary author group, international expert opinion, and use of current literature. DATA SYNTHESIS: We describe three common clinical scenarios when curative or life-prolonging goals of care are pursued despite a high likelihood of death. We explore the challenges to providing high-quality end-of-life care in this setting. We describe possible perspectives of families and ICU clinicians facing these circumstances to aid in our understanding of these complex deaths. Finally, we offer suggestions of how PICU clinicians might improve the care of children at the end of life in this setting. CONCLUSIONS: Merging curative interventions and optimal end-of-life care is possible, important, and can be enabled when clinicians use creativity, explore possibilities, remain open minded, and maintain flexibility in the provision of critical care medicine. When faced with real and perceived barriers in providing optimal end-of-life care, particularly when curative goals of care are prioritized despite a very poor prognosis, tensions and conflict may arise. Through an intentional exploration of self and others' perspectives, values, and goals, and working toward finding commonality in order to align with each other, conflict in end-of-life care may lessen, allowing the central focus to remain on providing optimal support for the dying child and their family.

A Case-Control Analysis of Postoperative Fluid Balance and Mortality After Pediatric Cardiac Surgery.

OBJECTIVES: A positive fluid balance after cardiac surgery may be associated with poor outcomes; however, previous studies looking at this association have been limited by the number of deaths in the study population. Our primary aim was to determine the relationship between postoperative cumulative fluid balance and mortality in cardiac surgical patients. Secondary aims were to study the association between fluid balance and duration of mechanical ventilation, intensive care and hospital length of stay. DESIGN: Case-control study. SETTING: A 30-bed multidisciplinary PICU. PATIENTS: All patients admitted to the PICU following cardiac surgery from 2010 to 2014. INTERVENTIONS: Deaths during PICU admission following cardiac surgery (cases) were matched 1:3 with children who survived to PICU discharge (controls) using the following criteria: age at surgery (within a 20% age range), Risk Adjusted Congenital Heart Surgery (RACHS-1) category, and year of admission. MEASUREMENTS AND MAIN RESULTS: Of 1,996 eligible children, 46 died (2.3%) of whom 45 (98%) were successfully matched. Cumulative fluid balance on days 2 and 7 was not associated with PICU mortality. On multivariable analysis, factors associated with mortality were cardiopulmonary bypass time (per 10-min increase, odds ratio [95% CI], 1.06 [1.00-1.12]; p = 0.03), extracorporeal membrane oxygenation requirement within 3 days (46.6 [9.47-230.11]; p < 0.001), peak serum chloride (mmol/L) in the first 48 hours (1.12 [1.01-1.23]), and time to start peritoneal dialysis after surgery (in comparison to no peritoneal dialysis, odds ratio [95% CI] in those started on early peritoneal dialysis was 1.07 [0.33-3.41]; p = 0.90 and in late peritoneal dialysis 3.65 [1.21-10.99]; p = 0.02). Children with cumulative fluid balance greater than or equal to 5% by day 2 spent longer on mechanical ventilation (median [interquartile range], 211 hr [97-539] vs 93 hr [34-225]; p <0.001), in PICU (11 d [8-26] vs 6 [3-13]; p < 0.001) and in hospital (22 d [13-39] vs 14 d [8-30]; p = 0.001). CONCLUSIONS: Early fluid overload is not associated with mortality. However, it is associated with increased duration of mechanical ventilation and PICU length of stay. Early peritoneal dialysis commencement (compared with late peritoneal dialysis) after surgery was associated with decreased mortality.

Extending the limits of extracorporeal membrane oxygenation: lung rest for a child with non-specific interstitial pneumonia.

OBJECTIVE: Veno-venous extracorporeal membrane oxygenation (ECMO) is an established therapy for the treatment of respiratory failure. Traditionally ECMO has been used to support patients with an acute, reversible disease process, with a predictable outcome. We report the successful use of veno-venous ECMO for an unusual indication. PATIENT: A 10-year old girl was admitted to intensive care with severe, hypoxic respiratory failure on the background of a 2-month history of worsening respiratory symptoms. She required high levels of conventional positive pressure ventilation, and high frequency oscillation. Lung biopsy confirmed a non-specific interstitial pneumonia, and the patient was commenced on immune suppressive therapy. Her clinical course was further complicated by pulmonary haemorrhage and severe air leak. INTERVENTIONS: On day 20 after admission the patient was placed on veno-venous ECMO for lung rest while awaiting a response to continued medical treatment. She required ECMO for 20 days, during which time sedation was reduced, and she was able to interact with those around her. The patient's ventilatory requirements after decannulation were minimal, and she subsequently made a steady clinical recovery. CONCLUSIONS: ECMO was safely and successfully used to provide a period of lung rest and time for medical therapy to take effect in a child with an unusual indication for support: a rare disease with an uncertain outcome on the background of prolonged mechanical ventilation.

Comparison of indirect methods of measuring intra-abdominal pressure in children.

OBJECTIVE: To determine the most accurate indirect method of measuring intra-abdominal pressure (IAP) in children. DESIGN AND SETTING: Single-centre, prospective, clinical study in a 23-bed specialist paediatric intensive care unit in Australia. PATIENTS AND PARTICIPANTS: 20 children admitted to paediatric intensive care with a peritoneal dialysis catheter in situ following congenital cardiac surgery. INTERVENTIONS: IAP was measured directly via the peritoneal dialysis catheter and by intragastric manometry via an indwelling nasogastric tube, and by intravesical manometry via an indwelling transurethral urinary catheter, using volumes of 0, 1, 3 and 5 ml/kg body weight of sterile saline instilled into the bladder. MEASUREMENTS AND RESULTS: Across the range of IAPs of 1-8 mmHg the Bland-Altman method for assessing agreement between two methods of clinical measurement showed bladder pressure measured via the urinary catheter with 1 ml/kg body weight of saline instilled to be the most accurate indirect measurement technique, tending to give pressures between 0.07 and 1.23 mmHg higher than the direct measurement (95% CI for bias). Measuring bladder pressure with either no saline instilled or more saline per kilogram body weight instilled was less accurate over the same range of pressures, as was measuring the gastric pressure. CONCLUSIONS: The most accurate indirect method of measuring IAP in children over the normal range of IAPs involves measuring bladder pressure via a transurethral urinary catheter with 1 ml/kg body weight of sterile saline instilled into the bladder.

Effect of peritoneal dialysis on intra-abdominal pressure and cardio-respiratory function in infants following cardiac surgery.

OBJECTIVE: To investigate the relationship between dialysate volume, intra-abdominal pressure, and cardio-respiratory function in infants following cardiac surgery. DESIGN: Prospective pilot study. SETTING: Paediatric intensive care unit. PATIENTS: Six infants undergoing peritoneal dialysis within 24 h of cardiopulmonary bypass. INTERVENTIONS: Manipulation of the volume of dialysate at levels of 0, 10, 20, and 30 ml/kg in variable order. MEASUREMENTS AND MAIN RESULTS: Intra-abdominal pressure was measured at each volume of dialysate via a pressure transducer connected to the dialysis catheter. Haemodynamic data was collected, including cardiac output, which was measured by thermodilution via a 3.5-French gauge catheter placed in the pulmonary arterial pathway. Respiratory data included PaO2, PaCO2, and dynamic compliance. Intra-abdominal pressure increased with increasing volume of dialysate (p < 0.001), though there was considerable variation between patients in the magnitude of increase. Intra-abdominal pressure remained low even with 30 ml/kg in the abdomen. In three infants, intra-abdominal pressure was re-measured in the absence of muscle relaxants, and was found to be higher in each case. No negative effects on cardiac output, markers of delivery of oxygen, or respiratory function were seen even at volumes of 30 ml/kg. Cardiac index was significantly higher with 10 ml/kg than when the abdomen was empty or contained a larger volume (p < 0.05). CONCLUSIONS: In this small group of infants, intra-abdominal pressure increased with increasing volumes of dialysate but remained low, even with 30 ml/kg in the abdomen, and was not associated with any deleterious effects on cardio-respiratory performance.

Sweat chloride: quantitative patch for collection and measurement.

OBJECTIVE: To compare two quantitative pilocarpine iontophoresis tests for sweat chloride. DESIGN: Simultaneous right and left arm sweat tests were done with the Gibson/Cooke and the CF quantum technologies. SETTING: Sweat tests were performed in a quality controlled cystic fibrosis (CF) sweat test laboratory by an experienced technologist at the University of Minnesota CF Center. PATIENTS: Patients referred for sweat tests as well as volunteer CF and control subjects (50 CF and 114 'normals') were tested. INTERVENTIONS: Standard procedures were used for the Gibson/Cooke test (GCST). The manufacturer of the CF quantum test (CFQT) provided factory standardized materials. MAIN OUTCOME MEASURES: Sweat chloride concentration, test time, failed tests, sensitivity, specificity, and cost. RESULTS: Duplicate test comparing the CFQT and the GCST revealed good comparability (R2 = 0.9434). Sensitivity and specificity of the two methods are comparable at about 94% and 99% respectively. Rate of failed tests was 1% for the CFQT and 15% for the GCST. The CFQT and the GCST are comparable (R2 = 0.9434). Sensitivity (94%) and specificity (99%) are the same for both tests. CONCLUSIONS: The CFQT method is equal in accuracy and reliability to the more labor-intensive and costly GCST. Advantages of the CFQT are: the small sample size required (three to ten mg), decreased operator dependence, simpler to perform, and requires less equipment. It could be used in a clinic setting to diagnose CF in patients with suggestive symptoms.

Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline.

In patients with cystic fibrosis, CF-related diabetes mellitus (CFRD) has been associated with increased morbidity and mortality. Whether glucose intolerance is also associated with poor outcomes is unclear. To better define these relationships we prospectively followed a group of 152 patients with CF without diabetes for 4 yr. Patients were classified as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CFRD without fasting hyperglycemia (CFRD-No FH). FEV(1), FVC, and body mass index (BMI) were measured at baseline and quarterly. At baseline 45% of the patients had NGT, 38.8% had IGT, and 15.8% had CFRD-No FH. FEV(1), FVC, and BMI at baseline were comparable among these groups (all p > 0.1). After 4 yr an overall decline in FEV(1) and FVC occurred, with no change in BMI. The rates of decline for FEV(1) and FVC correlated with the glucose tolerance groups, with the highest rates of decline occurring among the CFRD-No FH group. In addition, patients in the lowest quartile for insulin production at baseline experienced the highest rates of pulmonary function decline over time, suggesting a relationship between insulin deficiency and clinical deterioration. We conclude that the degree of glucose intolerance is a strong determinant of future lung function decline in patients with CF.

Eating disorders in patients with cystic fibrosis.

This study was designed to examine rates of eating disorders and psychopathology in patients with cystic fibrosis (CF). Fifty-eight CF patients and 43 healthy control participants were evaluated using structured psychiatric interviews and rating scales. Two control participants and no CF patients were diagnosed with an eating disorder. Additionally, 11 CF patients were diagnosed with one or more psychiatric disorders. Group means on the rating scales did not show clinically meaningful elevations in either group. These data indicate no evidence for elevated rates of eating disorders in CF patients. Similarly, rates of other psychiatric disorders in the CF group were not greater than the prevalence reported in the general population.

Risk of death in cystic fibrosis patients with severely compromised lung function.

BACKGROUND: Lung disease accounts for most of the mortality in patients with cystic fibrosis (CF). Lung transplantation is an option for patients severely impaired, being recommended when life expectancy is estimated to be <2 years. Our objectives were to evaluate in our patient population the validity of currently accepted criteria for low life expectancy and to identify other potentially useful criteria. METHODS: Data were retrieved from CF patients followed up at our center who reached and kept an FEV1 <30% predicted. A life table was created and stratified according to characteristics believed to be of importance. In addition, the rate of decline in percent predicted FEV1 was analyzed. These characteristics were evaluated as predictors of risk of death. RESULTS: The median survival was 3.9 years (95% confidence interval, 2.88 to 4.12 years), with no significant differences according to gender, nutritional status, presence of diabetes, or decade in which the patient was cared for. Only by age was there a significant difference in the median survival (p<0.05). By proportional hazards regression, only the rate of decline in percent predicted FEV1 was a significant predictor of the risk of death, with a borderline effect from younger age (p=0.06). CONCLUSION: In our patient population, a cutoff value of FEV1 of < 30% predicted is not a reliable predictor of high risk of death within 2 years. The yearly rate of decline of percent predicted FEV1 is a better parameter to identify those patients at high risk for death.

Cystic fibrosis-associated colitis and fibrosing colonopathy.

OBJECTIVE: To describe our experience with cystic fibrosis (CF)-associated colitis and fibrosing colonopathy, and to assess treatment strategies. STUDY DESIGN: We reviewed hospital charts and autopsy reports of all University of Minnesota patients with CF between 1975 and August 1994. We identified six patients with colonopathy and compared them with a cohort of 79 patients with CF in the same age range and seen during the same period. RESULTS: All patients with colonopathy had bloody diarrhea; five of the six had abdominal pain. Stool frequency and related symptoms distinguished the patients with colonopathy from the cohort population. All took a higher median dose of pancreatic enzymes than the cohort population during the 3 months preceding the onset of symptoms (p < 0.002). For all six patients, barium studies revealed loss of haustration, and shortening and diffuse narrowing of the colonic lumen with relative rectal sparing. The distal ileal mucosa was irregular in four patients. A histopathologic study reveal fibrosis of the submucosa or lamina propria, and focal acute cryptitis in all six patients. Other features included ascites (2/6) and nodular regenerative hyperplasia of the liver (1/6). One patient continues to have symptoms, three had subtotal colectomy, and the condition of two improved after a regimen including a low-fat diet, withholding of pancreatic enzymes, and supplemental parenteral nutrition was initiated. CONCLUSIONS: Fibrosing colonopathy represents a newly recognized gastrointestinal complication of cystic fibrosis. Affected persons have taken larger doses of pancreatic enzymes than similar patients with cystic fibrosis, and have bloody diarrhea. We developed a medical protocol that may avoid surgical resection of the colon in some of these patients.

Serum fatty acid profiles in cystic fibrosis patients and their parents.

Fatty acid compositions of the major serum lipid classes from 43 cystic fibrosis (CF) homozygotes (CF patients), 36 obligate heterozygotes (parents of CF patients) and 34 controls were determined by capillary gas chromatography. Fatty acid compositions of the homozygote CF patients were skewed in the direction of relative essential fatty acid deficiency in comparison with the controls. Less pronounced, but similar deviations from normal, were observed in the heterozygotes. Homozygotes with normal fatty acid compositions and heterozygotes with considerably disturbed fatty acid profiles were found.

Mucus transport mechanisms in relation to the effect of high frequency chest compression (HFCC) on mucus clearance.

High frequency chest compression (HFCC) appears promising as a form of chest physiotherapy. Studies published by several clinical centers support its efficacy, and further clinical data are expected to become available.

Family correlates of a 10-year pulmonary health trend in cystic fibrosis.

In this study, 33% of the variance in the 10-year trend of forced expiratory volume in 1 second (FEV1), used as an index of pulmonary health, was explained by differences in family characteristics at the start of the study. Balanced family coping, a family emphasis on personal growth, and compliance with treatment for 91 children with cystic fibrosis were assessed at the start of the study and the FEV1 was observed at every clinic visit over the next 10 years. When both parents' coping emphasized family integration, support for self, and medical consultation, the FEV1 trend was better. Compliance with daily chest physical therapy and with quarterly clinic visits was associated with a better FEV1 trend. Poorer FEV1 trend was associated with active social involvement of family members. Older patients and patients whose parents worked more hours outside the home had lower compliance. These findings support the importance of encouraging families to balance their resources between the child's health needs and family needs.

The impact of home monitoring and daily diary recording on patient status in cystic fibrosis.

An experimental home monitoring system for assessing the progress and planning changes in the care of patients with cystic fibrosis (CF) has been implemented at the University of Minnesota Cystic Fibrosis Center. One group of patients and families did daily recording of physical measurements and symptoms, and sent the diary to the data coordinating center weekly for analysis. The remaining patients were not part of the home monitoring program. Twenty-five patients were randomly selected from the home monitoring group. They were compared to an age- and sex-matched control group not doing home monitoring to ascertain if home self-measurement and daily diary recording, in the absence of any therapeutic intervention, produced any change in physical or psychological status, pulmonary function, or growth over a 4-year study period. Subjects ranged in age from 6 to 43 years. Clinical status was measured by the National Institutes of Health cystic fibrosis scoring system. Pulmonary function was assessed as percent of predicted forced vital capacity and percent of predicted forced expiratory volume in 1 sec (FEV1). Growth was analyzed as percent of predicted weight based on age-, sex-, and height-dependent equations. Psychological status was determined by self-assessment and referral for conseling. Only percent predicted FEV1 in the control group declined significantly. There were no statistically significant changes in any other measures either within or between diary and nondiary groups over the 4-year period.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term effect of high-frequency chest compression therapy on pulmonary complications of cystic fibrosis.

A high-frequency chest compression (HFCC) device for clearance of mucous secretions from airways was tested in 16 cystic fibrosis (CF) patients with significant improvement in pulmonary function for the HFCC period, which averaged 22 months per patient. The device consists of a variable air pulse delivery system and a non-stretch inflatable vest worn by the patient to cover the entire torso. The patients perform 30 minute therapy sessions divided into 5 minute periods at each of six frequencies. Individual patient therapy time per day ranged from 30 to 240 minutes. Frequencies used by each patient were determined by measuring air flow at the mouth and calculated volume expired per chest compression during tidal breathing while receiving HFCC at frequencies between 5 and 22 Hz at 1 Hz increments. The frequencies that produced the three highest flows and the three largest volumes were selected for each patient's therapy. Ninety-four percent of patients' regression line slopes for percent predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) became more positive during self-administered HFCC therapy as compared to slopes before HFCC therapy, when manual chest physical therapy was used. Two-sided t-test showed that the mean slopes were more positive for FVC and FEV1 during HFCC therapy than for the manual chest physical therapy period before HFCC therapy. The significance level for both FVC and FEV1 was at P less than 0.001.

Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study.

The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation.