超出生体重児に対する早期デキサメサゾン投与の有用性 : National Institute of Child Health and Human Development Neonatal research Network報告 (海外誌掲載論文の和文概要とそれに対するコメント)

Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention.

Mechanisms of Cisplatin nephrotoxicity.

Objective: T o de v elop a North American Society for Pediatric Ga str oen te rol og y , He pat olo gy , and Nut ri tio n (N ASP GH AN) and Eu rop ea n Soc ie ty fo r Pe di atr ic Gas tr oen te ro log y , Hep at ol og y , and Nut rit io n (ES PGH AN ) int er nat io nal con se ns us on th e di agn os is an d ma nag em ent of gas tr oes op hag eal refl ux and gas tr oes op hag eal re flu x di sea se in th e ped ia tr ic po pu la tio n. Methods: An international panel of 9 pediatric gastroenterologists and 2 epidemiologists were selected by both societies, which de v eloped these guidelines based on the Delphi principle. Statements were based on systematic literature searches using the best-av ailable e vidence from PubMed, Cumulati ve Index to Nursing and Allied Health Literature, and bibliographies. The committee con v ened in face-to-face meetings 3 times. Consensus was achie v ed for all recommendations through nominal group technique, a structured, quantitati v e method. Articles were e v aluated using the Oxford Centre for Evidence-based Medicine Le vels of Evidence. Using the Oxford Grades of Recommendation, the quality of e vidence of each of the recommendations made by the committee was determined and is summarized in appendices. Results: More than 600 articles were re vie wed for this work. The document provides e vidence-based guidelines for the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. Conclusions: Th is do cum ent is int end ed to be us ed in dai ly pra cti ce fo r th e de v el op me nt of fut ure cli ni cal pra ct ic e gu ide lin es and as a bas is for cli ni cal tr ia ls . JP GN 49 :49 8 – 54 7, 20 09 . Ke y Wo rd s: Cli nic al pra ct ic e gu id el ine s — Di agn os tic te sts — Ga str oes op hag ea l refl ux (GE R) — Ga str oes op hag ea l refl ux di sea se (GE RD ) — The rap eut ic mod al iti es. # 20 09 by Eu rop ea n Soc ie ty fo r Pe di atr ic Gas tr oen te ro log y , Hep at ol og y , and Nut rit io n and No rt h Am er ica n So ci ety for Pe dia tri c Ga str oen te rol og y , Hep at ol og y , an d Nu tr iti on

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Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)

Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.

/pdf/obesity-and-inflammation-the-linking-mechanism-and-the-19mr83znhx.pdf

Obesity and inflammation: the linking mechanism and the complications.

Context Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome primarily caused by maternal opiate use. No national estimates are available for the incidence of maternal opiate use at the time of delivery or NAS. Objectives To determine the national incidence of NAS and antepartum maternal opiate use and to characterize trends in national health care expenditures associated with NAS between 2000 and 2009. Design, Setting, and Patients A retrospective, serial, cross-sectional analysis of a nationally representative sample of newborns with NAS. The Kids' Inpatient Database (KID) was used to identify newborns with NAS by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code. The Nationwide Inpatient Sample (NIS) was used to identify mothers using diagnosis related groups for vaginal and cesarean deliveries. Clinical conditions were identified using ICD-9-CM diagnosis codes. NAS and maternal opiate use were described as an annual frequency per 1000 hospital births. Missing hospital charges ( Main Outcome Measures Incidence of NAS and maternal opiate use, and related hospital charges. Results The separate years (2000, 2003, 2006, and 2009) of national discharge data included 2920 to 9674 unweighted discharges with NAS and 987 to 4563 unweighted discharges for mothers diagnosed with antepartum opiate use, within data sets including 784 191 to 1.1 million discharges for children (KID) and 816 554 to 879 910 discharges for all ages of delivering mothers (NIS). Between 2000 and 2009, the incidence of NAS among newborns increased from 1.20 (95% CI, 1.04-1.37) to 3.39 (95% CI, 3.12-3.67) per 1000 hospital births per year (P for trend  Conclusion Between 2000 and 2009, a substantial increase in the incidence of NAS and maternal opiate use in the United States was observed, as well as hospital charges related to NAS.

/pdf/neonatal-abstinence-syndrome-and-associated-health-care-2crm396mzd.pdf

Neonatal Abstinence Syndrome and Associated Health Care Expenditures

Aims Infants of mothers who smoked during pregnancy have an increased risk of sudden infant death; a possible explanation is that such infants have neurodevelopmental abnormalities of ventilatory control. Our aim was to test the hypothesis that infants of mothers who had smoked antenatally compared to infants of non-smoking mothers would have a poorer ventilatory response to hypoxia. Methods Infants were recruited before maternity unit discharge and assigned to one of two groups based on maternal smoking history. A pneumotachograph and face mask were placed over the infant9s mouth and nose. During quiet sleep, the infants were switched from breathing room air to 15% oxygen (hypoxic challenge), which was maintained for five minutes unless the oxygen saturation level fell below 85%. Changes in oxygen saturation, heart rate, respiratory rate, tidal and minute volume and end tidal CO2 (ETCO2) were assessed. Results Ten infants of smoking mothers (median gestational age of 39 (36-41) weeks) and 10 infants of non smoking mothers (39 (37-42) weeks) were studied. The median birth weight of the infants of the smoking mothers was lower than that of infants of the non-smoking mothers (2450 (1924-3790) grams versus 3299 (2560-4320) grams, p=0.04). The infants were studied at similar postnatal ages (median 30 (10-120) versus 32 (10-100) hours), p=0.7. The two groups had comparable baseline tidal breathing, oxygen saturation, heart rate and ETCO2 levels. In response to the hypoxic challenge, the two groups had similar falls in their oxygen saturation and increases in heart rate. There was a biphasic response in minute ventilation to the hypoxic challenge. There was no significant differences in the initial percentage increase in minute ventilation between the two groups (median 29% (range 17-40) versus 23% (2-35), p=0.23, but the subsequent percentage decrease in minute volume in the infants of the smoking mothers was greater than that of the infants of the non-smoking mothers (median 32 % (range 0-99) versus 0%(−20-32)), p=0.03. Conclusion These results suggest intrauterine exposure to tobacco smoking may result in impairment of the infant peripheral chemoreceptor response.

https://adc.bmj.com/content/archdischild/97/Suppl_1/A1.2.full.pdf

Influence of antenatal smoking exposure on the newborn response to a hypoxic challenge

Aim Assist control ventilation (ACV) compared to pressure limited, time cycled ventilation is associated with shorter duration of weaning. During both ACV and pressure support ventilation (PSV), all the infant9s breaths are supported by positive pressure inflations but, during PSV, both the timing of the start and end of inflation are determined by the infant9s respiratory efforts and hence asynchrony may be less likely. Inflation times, however, can be short during PSV and this may increase the work of breathing and adversely affect respiratory muscle strength. The aims of this study, therefore, were to determine whether the duration of weaning differed between infants weaned by PSV or ACV and if any differences related to the differences in the work of breathing, asynchrony or respiratory muscle strength. Methods 36 infants, median gestational age 30 (range 21–39) weeks, were randomised to weaning by either ACV or PSV. The duration of weaning was recorded. At baseline (study entry), 24 h after entering the study and immediately prior to extubation using the transdiaphragmatic pressure time product (PTPdi), an assessment of the work of breathing, was measured. A dual tipped pressure transducer was used to measure oesophageal and gastric pressures and the transdiaphragmatic pressure calculated by digital subtraction of the oesophageal from the gastric pressure. PTPdi was calculated by integration of the transdiaphragmatic pressure signal with time for each breath and expressed per minute. The mean PTPdi was calculated from 20 consecutive breaths. In addition, asynchrony (TAA) was assessed using respiratory inductance plethysmography and respiratory muscle strength measured by recording the maximal inspiratory pressure produced during a maintained airway occlusion during crying (Pimax). Results The median duration of weaning was 33.7 (range 7–100) h in the ACV group and 26.7 (range 9.75–168.8) h in the PSV group (p=0.88). There were no significant differences in the median PTPdi, TAA or Pimax results between the two groups. Conclusion Weaning modes which support all of the infant9s breaths are equally efficacious.

https://adc.bmj.com/content/archdischild/96/Suppl_1/A34.3.full.pdf

Randomised trial comparing assist control and pressure support ventilation during weaning

Aim: Prematurely born infants frequently breathe while being mechanically ventilated and the pattern of the respiratory interaction influences outcome. The different interactions seen are the result of stimulation of respiratory reflexes (Head9s and the Hering-Breuer reflexes). Respiratory reflexes may be weaker in term born compared to prematurely born infants and thus may not influence the outcome of the former. The aim, therefore, of this study was to characterise any spontaneous respiratory efforts of mechanically ventilated infants born at term. Methods: To date, ten infants (median gestational age 38 weeks) have been studied at a median postnatal age of five days: five infants on intermittent positive pressure ventilation (IPPV) and five on synchronised intermittent mandatory ventilation (SIMV). Oesophageal, gastric and airway pressures, flow and volume were simultaneously recorded for at least 20 minutes, 100 consecutive breaths were analysed for each baby. Results: All the infants breathed during mechanical ventilation. Four patterns of interaction were noted: synchrony, augmented inspiration, active expiration, prolongation of expiration: Active expiration was significantly more common in the SIMV group (p Conclusions: Respiratory reflexes are provoked in term born infants by mechanical inflations. SIMV does not prevent active expiration, this may relate to trigger delay.

Spontaneous respiratory activity during mechanical ventilation of term born infants

Placental tissue: An unusual cause of tracheal obstruction

Aims: To determine the most appropriate level of volume targeting (VT) for ventilated infants born at or near term. Methods: Study one: expiratory tidal volumes (VTe) were measured during time cycled, pressure limited ventilation either using a pneumotachograph or the ventilator9s software; at least 80 breaths were analysed per infant. Study two: infants were studied at VT levels of 4, 5 and 6 mls/kg delivered in random order, with return to baseline between each VT level. The transdiaphragmatic pressure-time product (PTPdi), a measure of the work of breathing, was assessed at each VT level and during the baseline periods. To measure PTPdi, oesophageal and gastric pressures are measured and PTPdi calculated by integration of the transdiaphragmatic pressure signal with time for each breath and expressed per minute. In both studies, infants are only assessed when their blood gases are within the normal range. Results: To date: Study one: 20 infants, median gestational age of 39 (range 35-41) weeks, had a median VTe of 5 (range 1.4-9.7) mls/kg; 50% of infants had a VTe outside the “normal” tidal volume range (4 to 6mls/kg). Study two: the median PTPdi of 11 infants, median gestational age 39 (35-41) weeks, at a VT level of 4 mls/kg (310, IQR 244-332 cmH2O.s/min) was almost double that at 6 mls/kg (median 163, IQR 122-220 cmH2O.s/min), (p Conclusion: During time cycled, pressure limited ventilation, infants born at or near term are frequently ventilated using volumes outside the “normal” tidal range. Yet, even within that range, low compared to high levels of volume targeting significantly increase the work of breathing.

Simon Hannam

Papers

Influence of antenatal smoking exposure on the newborn response to a hypoxic challenge

Randomised trial comparing assist control and pressure support ventilation during weaning

Spontaneous respiratory activity during mechanical ventilation of term born infants

Placental tissue: An unusual cause of tracheal obstruction

Appropriate level of volume targeting for ventilated infants born at or near term