Roland Gerull

Toxic epidermal necrolysis and Stevens-Johnson syndrome: A review*

Objectives: The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome. Data Sources: PubMed was searched using the terms toxic epidermal necrolysis, Stevens-Johnson syndrome, drug toxicity, drug interaction, and skin diseases. Data Synthesis: Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute inflammatory skin reactions. The onset is usually triggered by infections of the upper respiratory tract or by preceding medication, among which nonsteroidal anti-inflammatory agents, antibiotics, and anticonvulsants are the most common triggers. Initially the diseases present with unspecific symptoms, followed by more or less extensive blistering and shedding of the skin. Complete death of the epidermis leads to sloughing similar to that seen in large burns. Toxic epidermal necrolysis is the most severe form of drug-induced skin reaction and includes denudation of >30% of total body surface area. Stevens-Johnson syndrome affects <10%, whereas involvement of 10%–30% of body surface area is called Stevens-Johnson syndrome/toxic epidermal necrolysis overlap. Besides the skin, mucous membranes such as oral, genital, anal, nasal, and conjunctival mucosa are frequently involved in toxic epidermal necrolysis and Stevens-Johnson syndrome. Toxic epidermal necrolysis is associated with a significant mortality of 30%–50% and long-term sequelae. Treatment includes early admission to a burn unit, where treatment with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. The mechanism of disease is not completely understood, but immunologic mechanisms, cytotoxic reactions, and delayed hypersensitivity seem to be involved. Conclusion: Profound knowledge of exfoliative skin diseases is needed to improve therapy and outcome of these life-threatening illnesses.

Oral Sucrose and “Facilitated Tucking” for Repeated Pain Relief in Preterms: A Randomized Controlled Trial

OBJECTIVES: To test the comparative effectiveness of 2 nonpharmacologic pain-relieving interventions administered alone or in combination across time for repeated heel sticks in preterm infants. METHODS: A multicenter randomized controlled trial in 3 NICUs in Switzerland compared the effectiveness of oral sucrose, facilitated tucking (FT), and a combination of both interventions in preterm infants between 24 and 32 weeks of gestation. Data were collected during the first 14 days of their NICU stay. Three phases (baseline, heel stick, recovery) of 5 heel stick procedures were videotaped for each infant. Four independent experienced nurses blinded to the heel stick phase rated 1055 video sequences presented in random order by using the Bernese Pain Scale for Neonates, a validated pain tool. RESULTS: Seventy-one infants were included in the study. Interrater reliability was high for the total Bernese Pain Scale for Neonates score (Cronbach’s α: 0.90–0.95). FT alone was significantly less effective in relieving repeated procedural pain (P < .002) than sucrose (0.2 mL/kg). FT in combination with sucrose seemed to have added value in the recovery phase with lower pain scores (P = .003) compared with both the single-treatment groups. There were no significant differences in pain responses across gestational ages. CONCLUSIONS: Sucrose with and without FT had pain-relieving effects even in preterm infants of <32 weeks of gestation having repeated pain exposures. These interventions remained effective during repeated heel sticks across time. FT was not as effective and cannot be recommended as a nonpharmacologic pain relief intervention for repeated pain exposure.

Physiological parameters after nonpharmacological analgesia in preterm infants: a randomized trial

To compare the influence of three different nonpharmacological interventions on cortical activation, heart rate and peripheral oxygen saturation (SaO2) after heelstick in preterm infants.

Incidence of retinopathy of prematurity (ROP) and ROP treatment in Switzerland 2006-2015: a population-based analysis

Background Retinopathy of prematurity (ROP) is a severe complication of preterm birth and can lead to severe visual impairment or even blindness if untreated. The incidence of ROP requiring treatment is increasing in some developed countries in conjunction with higher survival rates at the lower end of gestational age (GA). Material and methods The incidence of ROP and severe ROP (sROP) requiring treatment in Switzerland was analysed using the SwissNeoNet registry. We conducted a retrospective cohort analysis of very preterm infants with a GA below 32 weeks who were born between 2006 and 2015 in Switzerland. Patient characteristics were stratified according to GA. Results 9.3% and 1.8% of very preterm infants in Switzerland developed ROP of any stage and sROP, respectively. The incidence of ROP treatment was 1.2%. Patients with 24 and 25 weeks GA had the highest proportion of ROP treatment at 14.5% and 7.3%, respectively, whereas the proportion of treated infants at or above a GA of 29 weeks was 0.06%. Similarly, the risk of sROP declined strongly with increasing GA. During the observation period of 10 years, the incidence of ROP treatment ranged between 0.8% and 2.0%. Incidences of sROP or ROP treatment did not increase over time. Conclusion The incidence of ROP treatment in Switzerland is low and was stable over the analysed period. The low incidence of sROP in patients with a GA of 29 weeks or more leaves room for a redefinition of ROP screening criteria.

Increase of Caffeine and Decrease of Corticosteroids for Extremely Low Birthweight Infants with Respiratory Failure from 1997 to 2011

To compare treatment strategies for respiratory failure in extremely low‐birthweight (ELBW) infants in Germany in 1997 to Germany, Austria and Switzerland in 2011.

Do late preterm twins face an increased neonatal morbidity compared with singletons

OBJECTIVE Late preterm infants (born between 34 0/7 and 36 6/7 weeks of gestation) have been shown to have a higher morbidity and mortality than term infants. Furthermore, twins, both term and preterm, have a higher neonatal morbidity than singletons. The aim of our study was to examine if late preterm twins consequently have twice the neonatal morbidity when both risk factors prematurity and multiple pregnancy are present. STUDY DESIGN A retrospective single-centre study was conducted to compare neonatal outcome of late preterm singletons and late preterm twins born between 34 0/7 and 36 6/7 weeks of gestation as well as term twins with a gestational age from 37 0/7 to 41 6/7 weeks. Primary outcome was length of hospitalisation. Secondary outcome was neonatal morbidity. RESULTS A total of 845 infants were included. Late preterm twins (n = 243) were hospitalised significantly longer than term twins (n = 107) (13.5 ± 8.0 vs 6.29 ± 2.0 days, p <0.001) and late preterm singletons (n = 495) (13.5 ± 8.0 vs 12.6 ± 8.6 days, p = 0.011). Hyperbilirubinaemia occurred significantly more often in late preterm singletons than in late preterm twins (49.7 vs 29.2%; p<0.001). Otherwise, no significant differences were detected regarding neonatal morbidities or mortality of late preterm singletons and late preterm twins. Late preterm twins had a significantly higher incidence of most morbidities than term twins. CONCLUSION Late preterm twins are hospitalised significantly longer than similar-aged singletons, but have otherwise similar neonatal morbidities. Hyperbilirubinaemia is less frequent in late preterm twins than late preterm singletons.

Prediction of ROP Treatment and Evaluation of Screening Criteria in VLBW Infants-a Population Based Analysis

BackgroundThe incidence of retinopathy of prematurity (ROP) and ROP screening criteria differ between countries. We assessed whether ROP screening could be reduced based on the local ROP incidence.MethodsObservational cohort study of infants born in Switzerland between 2006 and 2015 <32 0/7 weeks. Chronological and postmenstrual ages at ROP treatment were analyzed. A model to identify ROP treatment on patients born between 2006 and 2012 (training set) was developed and tested on patients born between 2013 and 2015 (validation set).ResultsOf 7817 live-born infants, 1098 died within the first 5 weeks of life. The remaining 6719 infants were included into analysis. All patients requiring ROP treatment would have been identified if screening had been performed before reaching 60 days of life or 37 3/7 weeks postmenstrual age, whichever came first. The training and validation sets included 4522 and 2197 preterm infants encompassing 56 and 20 patients receiving ROP treatment, respectively. All patients would have required screening to reach 100% sensitivity. To reach a sensitivity of 95.0% and a specificity of 87.6%, we predicted a reduction in 13.2% of patients requiring screening (c-statistic = 0.916).ConclusionsA substantial reduction of infants requiring screening seems possible, but necessitates prospective testing of new screening criteria.

Less Oxygen, Later Intubation and Reduced Respiratory Pressures for ELBW Infants from 1997 to 2011

INTRODUCTION Evidence concerning delivery room management in extremely low birth weight infants (ELBW) has grown substantially within the last 20 years, leading to several guidelines and recommendations. However, it is unknown in which extent local treatment strategies have changed and if they reflect current recommendations. METHODS A detailed questionnaire about treatment strategies for ELBW infants was sent to all German neonatal intensive care units (NICUs) treating ELBW infants in 1997. A follow-up survey was conducted in 2011 and sent to all NICUs in Germany, Austria and Switzerland. RESULTS on delivery room management were compared to the first survey. RESULTS In 1997 and 2011, 63.6 and 66.2% of the approached hospitals responded. In 2011 similar results were observed between university and non-university hospitals as well as NICUs of different size. Differences between Germany, Austria and Switzerland were minimal. Changes over time were a lower initially applied fraction of inspired oxygen (FiO2) and peak inspiratory pressure (PiP) in 2011 compared to 1997. A longer time of apnea was tolerated before tracheal intubation is performed; the time of apnea was less frequently a sole criterion for intubation and surfactant was applied at lower FiO2 in 2011. The time of no thorax excursions and transport of the infant were considered an indication for intubation in 30.2 and 22.5%, and did not change in the observation period. CONCLUSION Treatment strategies for delivery room management in ELBW infants changed significantly between 1997 and 2011 and largely reflect current recommendations.

1631 Change of Habits after Years of Evidence: A Questionnaire on Neonatal Care

Background and Aims Evidence based knowledge in neonatal care has substantially increased during the last years. We tried to evaluate how well guidelines and evidence from studies have been implemented into clinical practice during the last 15 years. Methods Detailed questionnaires were sent 15 years apart to all neonatal units potentially treating VLBW infants in Germany (1995) and all German speaking countries (2010). Results The response rate was 66% both times. Whereas in 1995 2/3 of the units used 100% oxygen and ¼ 50% to start respiratory support in the delivery room, in 2010 only 3% and 5% of the units used 100% and 50% oxygen, respectively. Caffeine and Theophylline were used to treat apnoea of prematurity by 50% and 87% of the units in 1995 compared to 96% and 10% in 2010, respectively. Pasteurization of breast milk was done in 24% of the units in 1995 compared to 53% in 2010. In 1995, 37% of the units routinely used erythropoietin in ELBW infants compared to 27% in 2010. Conclusions Treatment of VLBW infants changed significantly within the last 15 years and some of the existing guidelines and evidence seem to be transferred into clinical practice in most units.