Exhaled Volatile Organic Compounds Precedes Pulmonary Injury in a Swine Pulmonary Oxygen Toxicity Model.

PURPOSE: Inspiring high partial pressure of oxygen (FiO2 > 0.6) for a prolonged duration can lead to lung damage termed pulmonary oxygen toxicity (PO2T). While current practice is to limit oxygen exposure, there are clinical and military scenarios where higher FiO2 levels and partial pressures of oxygen are required. The purpose of this study is to develop a non-invasive breath-based biomarker to detect PO2T prior to the onset of clinical symptoms. METHODS: Male Yorkshire swine (20-30 kg) were placed into custom airtight runs and randomized to air (0.209 FiO2, n = 12) or oxygen (>0.95 FiO2, n = 10) for 72 h. Breath samples, arterial blood gases, and vital signs were assessed every 12 h. After 72 h of exposure, animals were euthanized and the lungs processed for histology and wet-dry ratios. RESULTS: Swine exposed to hyperoxia developed pulmonary injury consistent with PO2T. Histology of oxygen-exposed swine showed pulmonary lymphatic congestion, epithelial sloughing, and neutrophil transmigration. Pulmonary injury was also evidenced by increased interstitial edema and a decreased PaO2/FiO2 ratio in the oxygen group when compared to the air control group. Breath volatile organic compound (VOC) sample analysis identified six VOCs that were combined into an algorithm which generated a breath score predicting PO2T with a ROC/AUC curve of 0.72 defined as a of PaO2/FiO2 ratio less than 350 mmHg. CONCLUSION: Exposing swine to 72 h of hyperoxia induced a pulmonary injury consistent with human clinical endpoints of PO2T. VOC analysis identified six VOCs in exhaled breath that preceded PO2T. Results show promise that a simple, non-invasive breath test could potentially predict the risk of pulmonary injury in humans exposed to high partial pressures of oxygen.

Early Acid Suppression Therapy Exposure and Fracture in Young Children.

BACKGROUND: Acid suppression therapy (AST), including proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs), is frequently prescribed to treat symptomatic gastroesophageal reflux in otherwise healthy infants. PPI use has been associated with increased fracture risk in older adults; 2 preliminary studies in children have conflicting results. METHODS: A retrospective cohort of children born 2001 to 2013 who were followed for ≥2 years was formed. Those with osteogenesis imperfecta, cholestasis, or child maltreatment were excluded. Prescription data were used to identify AST prescription before age 1 year. International Classification of Diseases, Ninth Revision, Clinical Modification codes identified fractures after age 1 year. A Cox proportional hazard analysis assessed fracture hazard and was adjusted for sex, prematurity, low birth weight, previous fracture, anti-epileptics, and overweight or obesity. RESULTS: Of 851 631 included children, 97 286 (11%) were prescribed AST in the first year of life; 7998 (0.9%) children were prescribed PPI, 71 578 (8%) were prescribed H2RA, and 17 710 (2%) were prescribed both a PPI and H2RA. Infants prescribed AST had an earlier median first fracture age (3.9 vs 4.5 years). After adjustment, increased fracture hazard was associated with PPI use (21%) and PPI and H2RA use (30%), but not H2RA use alone. Longer duration of AST treatment and earlier age of first AST use was associated with increased fracture hazard. CONCLUSIONS: Infant PPI use alone and together with H2RAs is associated with an increased childhood fracture hazard, which appears amplified by days of use and earlier initiation of ASTs. Use of AST in infants should be weighed carefully against possible fracture.

Prematurity Does Not Increase Early Childhood Fracture Risk.

OBJECTIVE: To evaluate the impact of prematurity on fracture by age 5, controlling for medications and comorbidities of prematurity. STUDY DESIGN: We performed a retrospective cohort study of infants born in Military Treatment Facilities in 2009-2010 with ≥5 years of follow-up care. Gestational age, low birth weight, comorbidities of prematurity (osteopenia, necrotizing enterocolitis, chronic lung disease, and cholestasis) and fractures were identified by International Classification of Disease, 9th Edition, codes. Pharmaceutical records identified treatment with caffeine, diuretics, postnatal corticosteroids, and antacids. Poisson regression analysis determined fracture rate by 5 years of life. RESULTS: There were 65 938 infants born in 2009-2010 who received care in the military health system for ≥5 years, including 3589 born preterm; 165 born at ≤286/7 weeks of gestation, 380 born at 29-316/7 weeks of gestation, and 3044 born at 32-366/7 weeks of gestation. Preterm birth at any gestational age was not associated with fracture rate in adjusted models. The fracture rate was increased with cholestasis, proton pump inhibitor exposure, and male sex. CONCLUSIONS: Prematurity was not associated with fracture rate. Neonatal cholestasis and proton pump inhibitor treatment were associated with increased fractures by age 5.

The development of pediatric anesthesia and intensive care in Scandinavia.

The initiation and development of pediatric anesthesia and intensive care have much in common in the Scandinavian countries. The five countries had to initiate close relations and cooperation in all medical disciplines. The pediatric anesthesia subspecialty took its first steps after the Second World War. Relations for training and exchange of experiences between Scandinavian countries with centers in Europe and the USA were a prerequisite for development. Specialized pediatric practice was not a full-time position until during the 1950s, when the first pediatric anesthesia positions were created. Scandinavian anesthesia developed slowly. In contrast, Scandinavia pioneered both adult and certainly pediatric intensive care. The pioneers were heavily involved in the teaching and training of anesthetists and nurses. This was necessary to manage the rapidly increasing work. The polio epidemics during the 1950s initiated a combination of clinical development and technical innovations. Blood gas analyses technology and interpretation in combination with improved positive pressure ventilators were developed in Scandinavia contributing to general and pediatric anesthesia and intensive care practice. Scandinavian specialist training and accreditation includes both anesthesia and intensive care. Although pediatric anesthesia/intensive care is not a separate specialty, an 'informal accreditation' for a specialist position is obtained after training. The pleasure of working in a relatively small group of devoted colleagues and staff has persisted from the pioneering years. It is still one of the most inspiring and pleasant gifts for those working in this demanding specialty.

Psychiatric outcome after severe cardio-respiratory failure treated with extracorporeal membrane oxygenation: a case-series.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used to save patients with severe cardiopulmonary failure at high risk of dying, but the long-term psychiatric outcome of the treatment has not been studied. METHODS: Twenty-eight adults who survived ECMO were subjected to psychiatric assessment 5 years after ECMO by means of interviews (MINI-Neuropsychiatric Interview and Montgomery-Åsberg Depression Rating Scale) and psychometrics [Neuroticism and social conformity (EPQ-N+L); General Health Questionnaire (GHQ), Hospital Anxiety Depression Scale; Aggression Questionnaire, Toronto Alexithymia Scale, and Giessener somatic symptom checklist (GBB)]. RESULTS: Fifteen patients (54%) suffered lifetime psychiatric disorders prior to ECMO. After ECMO, 11 subjects (39%) developed new psychiatric disorders, mostly organic mental (18%), obsessive-compulsive disorders (OCD) 15%, and/or post-traumatic stress disorders (PTSD) 11%. These 11 patients reported higher scores on Montgomery-Åsberg Depression Rating Scale (MADRS), GHQ, EPQ-N, and GBB. Disregarding the presence of psychiatric disorders at follow-up, ECMO patients reported high levels of distress, physical aggression, anger, and alexithymic traits. CONCLUSIONS: Severe life-threatening cardiovascular or pulmonary failure with subsequent ECMO is associated with an increased prevalence of long-term psychiatric disorders and distress. Studies addressing the etiology and prevalence of psychiatric consequences after ECMO are needed.

Skin conductance versus the modified COMFORT sedation score as a measure of discomfort in artificially ventilated children.

OBJECTIVE: We wanted to use skin conductance as a measure of increased stress in artificially ventilated children. The aim was to examine how changes in skin conductance, arterial blood pressure, and heart rate are associated with changes in the modified COMFORT sedation score during suction from the trachea. Nociceptive stimulation induces an outgoing sympathetic nervous burst to the skin and the palmar and plantar sweat glands are filled, which creates a skin conductance fluctuation. METHODS: Twenty children who were 1 day to 11 years of age were studied. All patients were artificially ventilated and circulatory stable. The data were obtained before, during, and 10 minutes after endotracheal suction. The number of skin conductance fluctuations, the amplitude of skin conductance fluctuations, the mean skin conductance level, arterial blood pressure, heart rate, and the modified COMFORT sedation score were recorded and tested from before to during and from during to after suction in the trachea. RESULTS. The number of skin conductance fluctuations, mean skin conductance level, arterial blood pressure, and the modified COMFORT sedation score increased during suction in the trachea, in contrast to heart rate and amplitude of skin conductance fluctuations. The number of skin conductance fluctuations from before to during and from during to after endotracheal suctioning correlated with changes in the modified COMFORT sedation score. This was in contrast to the other variables that did not. CONCLUSIONS: The number of skin conductance fluctuations during endotracheal suctioning showed better correlation with the increase in the modified COMFORT sedation score than heart rate and arterial blood pressure. Thus, the number of skin conductance fluctuations seems to be an objective supplement to the modified COMFORT sedation score for monitoring increased stress in artificially ventilated and circulatory stable children.

Clinical and psychosocial follow-up study of children treated with extracorporeal membrane oxygenation.

BACKGROUND: Serious heart and pulmonary failure may be treated with extracorporeal membrane oxygenation (ECMO). The aim of this follow-up study was a multimodal assessment of outcome in children surviving ECMO at our hospital from 1991 to 2004. METHODS: Twenty-two children were, on average, 1.18 years old (SD = 1.92; range, 0.1 to 7.8) when ECMO was initiated. Average age at follow-up was 7.2 years (range, 1.8 to 13.9). Thirteen children were treated for cardiac and nine for pulmonary failure. Venoarterial ECMO was performed in 21 patients and venovenous ECMO in one patient. The protocol included a review of patients records, clinical, neurologic and neuropsychologic, and radiological examinations, electroencephalogram, and interviews with the parents. RESULTS: Moderate or severe impairment in at least two clinical assessments were found in 16 (72.7%) children. Five (22.7%) children had cerebral palsy and 15 (68.2%) had moderate or severe cognitive impairment. Eight (36%) children had pathological radiologic findings. Pathological electroencephalograms were found in 11 (50%) patients including four (18.2%) with epileptic activity. Children with radiologic findings had a slightly worse cognitive outcome. There was no association between the neurophysiologic findings and the neuropsychologic performance or the radiologic findings. Based on parental assessment, only four children had pathological scores. CONCLUSIONS: All children, except for two, came walking to the follow-up visit. All parents were positive to the ECMO treatment, and reported a good or slightly reduced quality of life for their child. Cerebral sequelae were frequently found in children treated with ECMO. The need for treatment and support should be assessed in order to optimize their physical and psychosocial functioning.

Is it possible to predict outcome in cardiac ECMO? Analysis of preoperative risk factors.

BACKGROUND: Serious heart failure may be treated with extracorporeal membrane oxygenation (ECMO) when other treatment fails. The aim of the present study was to analyse preoperative risk factors of early mortality in patients treated with veno-arterial (VA)-ECMO. METHODS: We studied a total of 18 possible risk factors in 80 patients with severe cardiac insufficiency treated with VA-ECMO. All consecutive cases treated at our institution between Sept.1990 and May 2006 were included. Univariate analysis and multiple logistic regression analysis were performed on 16 risk factors. The endpoint was early mortality (any death within 30 days of ECMO treatment). RESULTS: Thirty patients (37.5%) died within 30 days. Age, gender, cause of cardiac failure, pre-ECMO treatment (ventilator, NO, IABP) did not significantly influence early mortality. A higher SvO2 was associated with survival and remained significant in the multivariate analysis. CONCLUSION: Treatment with VA-ECMO in patients with severe cardiac failure may save lives. It is, however, difficult to predict outcome. In this study, only SvO2 values prior to ECMO were positively associated with survival.

Cerebral outcome in adult patients treated with extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) carries a high risk of brain injury. The aim of this study was to determine the cerebral status in 28 adult survivors on average 5.0 (range, 0.5 to 12) years after ECMO treatment for severe cardiorespiratory failure. METHODS: All 28 patients were investigated at our institution. A comprehensive assessment protocol included a medical history, physical examination, neuropsychological assessment, electroencephalography, and neuroradiologic assessment. RESULTS: All patients were ambulant unaided, and 43% were without any clinical findings. Impaired neuropsychological performance was found in 41%, neuroradiologic findings in 52%, and a pathologic electroencephalogram in 41% of the patients. There was a significant correlation between the cognitive outcome and neuroradiologic findings. The incidence of neuroradiologic findings (cerebral infarction, microemboli or hemorrhage) was significantly higher in the venoarterial group compared with the venovenous group (75% versus 17%). There was no correlation between the type of ECMO and neuropsychological impairment. Electroencephalography findings did not correlate with neuropsychological performance, nor with the neuroradiologic findings. CONCLUSIONS: Late cerebral sequelae were frequently seen in patients treated on venoarterial ECMO. A significant correlation was found between cognitive impairment and neuroradiologic findings.

Congenital diaphragmatic hernia: a survey of practice in Scandinavia.

There is no consensus on the treatment of congenital diaphragmatic hernia (CDH), and practice seems to vary between centres. The main purpose of the present study was to survey current practice in Scandinavia. Thirteen paediatric surgical centres serving a population of about 22 million were invited, and all participated. One questionnaire was completed at each centre. The questionnaire evaluated management following prenatal diagnosis, intensive care strategies, operative treatment, and long-term follow-up. Survival data (1995-1998) were available from 12 of 13 centres. Following prenatal diagnosis of CDH, vaginal delivery and maternal steroids were used at eight and six centres, respectively. All centres used high-frequency oscillation ventilation (HFOV), nitric oxide (NO), and surfactant comparatively often. Five centres had extracorporeal membrane oxygenation (ECMO) facilities, and four centres transferred ECMO candidates. The majority of centres (7/9) always tried HFOV before ECMO was instituted. Surgery was performed when the neonate was clinically stable (11/13) and when no signs of pulmonary hypertension were detected by echo-Doppler (6/13). The repair was performed by laparotomy at all centres and most commonly with nonabsorbable sutures (8/13). Thoracic drain was used routinely at seven centres. Long-term follow-up at a paediatric surgical centre was uncommon (3/13). Only three centres treated more than five CDH patients per year. Comparing survival in centres treating more than five with those treating five or fewer CDH patients per year, there was a tendency towards better survival in the higher-volume centres (72.4%) than in the centres with lower volume (58.7%), p =0.065.