Thomas M. Berger

Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention Trial

Background: Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success. Objective: To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis. Methods: This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children’s Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age ≧34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48–72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values. Results: 121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics ≧72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12–0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events. Conclusion:Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.

Fatal varicella-zoster virus antigen-positive giant cell arteritis of the central nervous system

47:1441–6. 21. Zamora RL, Del Priore LV Storch GA, Gelb LD, Sharp J. Multiple recurrent branch retinal artery occlusions associated with varicella zoster virus. Retina 1996;16:399–404. 22. Gray F, Belec L, Lescsc MC, et al. Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome. Brain 1994;117:987–99. 23. Kleinschmidt-deMasters BK, Amlie-Lefond C, Gilden DH. The patterns of varicella-zoster virus encephalitis. Hum Pathol 1996;27:927–38. 24. Frank Y, Lim W, Kahn E, et al. Multiple ischemic infarcts in a child with acquired immunodeficiency syndrome, varicella zoster infection, and cerebral vasculitis. Pediatr Neurol 1989; 5:64–7. 25. Frank Y, Lu D, Pavlakis S, Black K, LaRussa P, Hyman RA. Childhood AIDS, varicella zoster, and cerebral vasculopathy. J Child Neurol 1997;12:464–6. 26. Sebire G, Meyer L, Chabrier S. Varicella as a risk factor for cerebral infarction in childhood: a case-control study. Ann Neurol 1999;45:679–80.

Survival rates of extremely preterm infants (gestational age < 26 weeks) in Switzerland: impact of the Swiss guidelines for the care of infants born at the limit of viability

Background: Because ethical decision making in the care of extremely preterm infants varies widely across Europe, the Swiss Society of Neonatology decided to publish its own guidelines on the care of infants born at the limit of viability in 2002. Objective: To examine the potential impact of the guidelines on survival rates, short-term complication rates and centre-to-centre outcome differences of extremely preterm infants (22–25 completed weeks). Design: Population-based, retrospective cohort study. Setting: All nine level III neonatal intensive care units (NICU) and affiliated paediatric hospitals in Switzerland. Patients: 516 extremely preterm infants born alive between 1 January 2000 and 31 December 2004. Main outcome measures: Delivery room and NICU mortality rates, survival to hospital discharge and incidence of short-term complications in survivors were assessed. To study the impact of the guidelines, two cohorts from two different time periods were compared (years 2000/2001, n = 220; years 2003/2004, n = 204) whereas patients born in the year of the publication (2002, n = 92) were excluded. For centre-to-centre comparisons, the entire population (n = 516) was analysed. Results: There was a significant increase in survival rates of extremely preterm infants from 31% to 40% (RR 1.24, 95% CI 1.02, 1.50) after the publication of the Swiss guidelines. This improvement was largely explained by significantly improved survival from 42% to 60% (p = 0.01) among infants born at 25 completed weeks because of decreased NICU mortality. Improved survival was not associated with statistically significant changes in the incidence of short-term complications. Despite national guidelines, considerable centre-to-centre outcome differences have persisted. Conclusions: The publication of the Swiss guidelines was followed by significantly improved survival of extremely preterm infants but had no impact on centre-to-centre differences.

Impact of Improved Survival of Very Low-Birth-Weight Infants on Incidence and Severity of Bronchopulmonary Dysplasia

BACKGROUND It has been suggested that improved survival of very low birth weight (VLBW) infants may have resulted in increased numbers of patients with bronchopulmonary dysplasia (BPD). GOAL To determine the impact of changes in mortality on the incidence and/or severity of BPD in three different time periods with distinct respiratory support strategies. METHODS Retrospective single center cohort study of VLBW infants: Cohort A (1986-1990): pre-surfactant era, use of conventional intermittent mandatory ventilation (IMV); cohort B (1993-1994): use of synthetic surfactant, nasopharyngeal continuous positive airway pressure (CPAP) and conventional IMV; cohort C (2000-2001): use of natural surfactant, early nasal prong CPAP, synchronized IMV with tidal volume monitoring and high frequency oscillatory ventilation (HFOV). BPD was classified as mild, moderate or severe according to Jobe and Bancalari. RESULTS The median gestational ages and birth weights were 28 3/7 weeks and 1,120 g for cohort A (n = 97), 30 0/7 weeks and 1,340 g for cohort B (n = 100), and 29 1/7 weeks and 1,200 g for cohort C (n = 135). The use of partial or complete courses of antenatal corticosteroids (ANC) increased over time (58%, 72%, and 82%, p = 0.003). There was a 50% reduction of mortality between each time period with mortality rates of 30%, 14% and 7% in cohorts A, B and C, respectively (p < 0.001). The overall incidence of BPD was 26% in the pre-surfactant era, 11% during the mid-1990s and 19% in the most recent time period (r = -0.05, p = 0.36). Moderate and severe forms of BPD decreased over time and were seen in 11% in cohort A, 3% in cohort B and 2% in cohort C (p = 0.008). CONCLUSION Changes in neonatal care of VLBW infants, including increased use of ANC and modified respiratory support strategies, have resulted in dramatically improved survival rates over the past 15 years without increasing moderate to severe pulmonary morbidity.

Caudal blocks: Caudal blocks

Caudal anesthesia is the single most important pediatric regional anesthetic technique. The technique is relatively easy to learn (1), has a remarkable safety record (2), and can be used for a large variety of procedures. The technique has been reviewed in the English (3) and French (4) literature, as well as in German guidelines (5) and in pediatric anesthesia textbooks (6).

Causes and Circumstances of Neonatal Deaths in 108 Consecutive Cases over a 10-Year Period at the Children’s Hospital of Lucerne, Switzerland

Background: Neonatal deaths still represent the largest percentage of overall childhood mortality. Many deaths of neonates are preceded by end-of-life decisions; however, decision-making practices have been reported to vary widely from country to country. Objectives: To analyze principal causes and circumstances of all consecutive neonatal deaths at our institution over a 10-year period. Methods: All neonates who had died either in the delivery room (DR) or the neonatal intensive care unit (NICU) between January 1, 1997 and December 31, 2006 were identified. Demographic information, principal causes and circumstances of death were abstracted from the individual medical records. Results: There were approximately 72,000 live births in the catchment area of our center with 15,150 deliveries occurring at the Women’s Hospital of Lucerne. Of the 108 deaths identified, 29 occurred in the DR (DR mortality rate 0.2%) and 79 in the NICU (NICU mortality rate 2.3%). The majority of DR deaths occurred in the setting of primary nonintervention and were related to extreme prematurity (n = 20), lethal congenital malformations (n = 6) and trisomy 13 (n = 2). One patient with severe perinatal asphyxia died despite full resuscitative efforts. In the NICU, overall mortality rate was inversely related to gestational age (GA). Cardiovascular and respiratory system failures were the predominant causes of death in premature infants with a GA <32 weeks, whereas CNS catastrophes accounted for the majority of deaths in the more mature NICU population. End-of-life decisions were common with less than 10% of deaths occurring despite maximal intensive care. Conclusions: In our perinatal center, primary nonintervention and redirection of care are the most common circumstances of death in neonates. This reflects our belief that, apart from futility, quality-of-life considerations are an important part of decision making in neonatology.

Hepatic capillariasis in a 1-year-old child

We describe the 2nd European case of hepatic capillariasis. The diagnosis of this parasitosis caused byCapillaria hepatica was made by needle biopsy of the liver in a 1-year-old girl who presented with a triad of persistent fever, hepatomegaly and hypereosinophilia. The child recovered completely after treatment with thiabendazole (Mintezol, Merck, Sharp and Dohme, Hoddeston, UK).

Fiberoptic intubation through the laryngeal mask airway (LMATM) as a standardized procedure

(spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal hernioraphy in early infancy. Cochrane Database Syst Rev 2003; 3: CD003669. 3 Sartorelli KH, Abajian JC, Kreutz JM, et al. Improved outcome utilizing spinal anesthesia in high-risk infants. J Pediatr Surg 1992; 27: 1022–1025. 4 William JM, Stoddart PA, Williams SA, et al. Post-operative recovery after inguinal herniotomy in ex-premature infants: comparison between sevoflurane and spinal anaesthesia. Br J Anaesth 2001; 86: 366–371.

Trends and centre-to-centre variability in survival rates of very preterm infants (<32 weeks) over a 10-year-period in Switzerland.

Background The publication of Swiss guidelines for the care of infants at the limit of viability (22–25 completed weeks) was followed by increased survival rates in the more mature infants (25 completed weeks). At the same time, considerable centre-to-centre (CTC) differences were noted. Objectives To examine the trend of survival rates of borderline viable infants over a 10-year-period and to further explore CTC differences. Design Population-based, retrospective cohort study. Setting All nine level III neonatal intensive care units (NICUs) and affiliated paediatric hospitals in Switzerland. Patients 6532 preterm infants with a gestational age (GA) <32 weeks born alive between 1 January 2000 and 31 December 2009. Main outcome measures Trends of GA-specific delivery room and NICU mortality rates and survival rates to hospital discharge were assessed. For CTC comparisons, centre-specific risk-adjusted ORs for survival were calculated in three GA groups: A: 23 0/7 to 25 6/7 weeks (n=976), B: 26 0/7 to 28 6/7 weeks (n=1943) and C: 29 0/7 to 31 6/7 weeks (n=3399). Results Survival rates of infants with a GA of 25 completed weeks which had improved from 42% in 2000/2001 to 60% in 2003/2004 remained unchanged at 63% over the next 5 years (2005–2009). Statistically significant CTC differences have persisted and are not restricted to borderline viable infants. Conclusions In Switzerland, survival rates of infants born at the limit of viability have remained unchanged over the second half of the current decade. Risk-adjusted CTC outcome variability cannot be explained by differences in baseline demographics or centre case loads.

Neonatal dexamethasone induces premature microvascular maturation of the alveolar capillary network.

Postnatal glucocorticoid treatment of preterm infants was mimicked by treating newborn rats with dexamethasone (0.1–0.01 μg/g, days 1–4). This regimen has been shown to cause delayed alveolarization. Knowing that microvascular maturation (transformation of double‐ to single‐layered capillary networks in alveolar septa) and septal thinning prevent further alveolarization, we measured septal maturation on electron photomicrographs in treated and control animals. In treated rats and before day 10, we observed a premature nonreversing microvascular maturation and a transient septal thinning, which both appeared focally. In vascular casts of both groups, we observed contacts between the two capillary layers of immature alveolar septa, which were predictive for capillary fusions. Studying serial electron microscopic sections of human lungs, we were able to confirm the postulated fusion process for the first time. We conclude that alveolar microvascular maturation indeed occurs by capillary fusion and that the dexamethasone‐induced impairment of alveolarization is associated with focal premature capillary fusion. Developmental Dynamics 233:1261–1271, 2005.