今日の臨床サポート

無呼吸発作(小児科)

著者: 垣内五月 東京大学病院小児科

監修: 渡辺博 帝京大学老人保健センター

著者校正/監修レビュー済:2021/01/07
患者向け説明資料

概要・推奨   

  1. 腹臥位における呼吸においては胸郭と腹部が同期して動くことにより、呼吸パターンやSpO2に影響することなく胸壁が安定化する。腹臥位によって無呼吸発作の頻度は減少する(推奨度1)
  1. 4~6cmH2OのCPAPは、無呼吸発作に対する有効かつ安全な治療法である(推奨度2)
  1. 無呼吸発作に対して経鼻的間欠的陽圧呼吸法(NIPPV)は有効であるが、その有効性はNasal DPAPに比較すると劣っている(推奨度3)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
  1. 閲覧にはご契約が必要となります。閲覧に はご契約が必要となります。閲覧にはご契約が必要となります 。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
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  1. 低濃度(0.8%)のCO2吸入は短期的にはテオフィリン投与と同等の効果が認められる(推奨度3)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
垣内五月 : 特に申告事項無し[2021年]
監修:渡辺博 : 特に申告事項無し[2021年]

改訂のポイント:
  1. ハイフローネーザルカヌラの追加、CPAPにbiphasic modeの追加、ドキサプラムの追加を行った。
 

病態・疫学・診察

疾患(疫学・病態)  
  1. 無呼吸発作は早産児によく認められる問題であり、早産に伴う特発性の無呼吸か、または何らかの合併症による無呼吸である。正期産児の無呼吸は常に異常であり直ちに診断・評価が必要である。
  1. 無呼吸は睡眠の状態に依存しており、REM睡眠の間は無呼吸の頻度が増加する。逆説的な胸郭運動(吸気時に腹部が膨隆し、胸壁が下がる)はREM睡眠の間に起こりやすく、換気血流比の低下(吸気で肺血流は増加するが換気は低下するため)によるPaO2の低下を引き起こす。
問診・診察のポイント  
問診:
  1. 妊娠歴(無呼吸発作は早産児によく認められる問題であり、早産に伴う特発性の無呼吸か、または何らかの合併症による無呼吸である。正期産児の無呼吸は常に異常であり直ちに診断・評価が必要である。)

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Tracy R Sher
雑誌名: Pediatr Phys Ther. 2002 Summer;14(2):112-3. doi: 10.1097/00001577-200214020-00008.
Abstract/Text
PMID 17053691  Pediatr Phys Ther. 2002 Summer;14(2):112-3. doi: 10.109・・・
著者: C Reher, K D Kuny, T Pantalitschka, M S Urschitz, C F Poets
雑誌名: Arch Dis Child Fetal Neonatal Ed. 2008 Jul;93(4):F289-91. doi: 10.1136/adc.2007.132746. Epub 2008 Feb 19.
Abstract/Text BACKGROUND: Apnoea of prematurity has been shown to respond to changes in posture.
OBJECTIVE: To investigate the effect of three postural interventions on the rate of bradycardia and desaturation events.
METHODS: 18 infants (< or =32 weeks' gestational age; 11 boys) with apnoea of prematurity underwent recordings of breathing movements, electrocardiogram and instantaneous heart rate, pulse oximeter saturation (SpO2), photoplethysmographic waveforms and digital video frame while in one of three different prone positions. The following interventions were applied in random order: horizontal position (HP), 15 degrees head-up tilt position (TP) and three-level position (3P) according to Kinaesthetics Infant Handling. The primary study variable was the combined event rate of desaturations (SpO2 <85%) and bradycardias (heart rate <80 bpm). One secondary study variable was the duration of body movements.
RESULTS: The median (range) combined event rate was 26.7/h (0.3-72.7) in HP, 25.2/h (0.3-70.5) in TP and 21.2/h (0-66.3) in 3P (p>0.05). The median (range) duration of body movements was 10.8 s/h (0-48.2) in HP, 7.1 s/h (0-72.4) in TP and 7.0 s/h (0-47.7) in 3P (p>0.05).
CONCLUSIONS: No significant advantage of a head-up tilt or a three-level position over a standard horizontal position could be confirmed.

PMID 18285373  Arch Dis Child Fetal Neonatal Ed. 2008 Jul;93(4):F289-9・・・
著者: Susan M Ludington-Hoe, Gene Cranston Anderson, Joan Y Swinth, Carol Thompson, Anthony J Hadeed
雑誌名: Neonatal Netw. 2004 May-Jun;23(3):39-48. doi: 10.1891/0730-0832.23.3.39.
Abstract/Text PURPOSE: To determine the safety and effects on healthy preterm infants of three continuous hours of kangaroo care (KC) compared to standard NICU care by measuring cardiorespiratory and thermal responses.
DESIGN: Randomized controlled trial-pretest-test-posttest control group design.
SAMPLE: Twenty-four healthy preterm infants (33-35 weeks gestation at birth) nearing discharge. Eleven of the infants received KC; 13 received standard NICU care.
MAIN OUTCOME VARIABLES: Heart rate, respiratory rate, oxygen saturation, and abdominal skin temperature were manually recorded every minute. Apnea, bradycardia, periodic breathing, and regular breathing were captured continuously on a pneumocardiogram printout. Three consecutive interfeeding intervals (three hours each) on one day constituted the pretest, test, and posttest periods.
RESULTS: Mean cardiorespiratory and temperature outcomes remained within clinically acceptable ranges during KC. Apnea, bradycardia, and periodic breathing were absent during KC. Regular breathing increased for infants receiving KC compared to infants receiving standard NICU care.

PMID 15182119  Neonatal Netw. 2004 May-Jun;23(3):39-48. doi: 10.1891/0・・・
著者: Bettina Bohnhorst, Diana Gill, Michael Dördelmann, Corinna S Peter, Christian F Poets
雑誌名: J Pediatr. 2004 Oct;145(4):499-502. doi: 10.1016/j.jpeds.2004.06.019.
Abstract/Text OBJECTIVE: We recently found increased temperature and increased bradycardia and desaturation during skin-to-skin care (SSC). We wanted to determine if these effects were related.
STUDY DESIGN: Twenty-two infants (median gestational age at birth 28.5 weeks [range 24-31], median age at study 25.5 days [range 10-60 days], median birth weight 1025 g [range 550-1525 g], median weight at study 1320 g [range 900-2460 g]) underwent three 2-hour recordings of breathing movements, nasal airflow, heart rate, and pulse oximeter saturation (SpO 2 ): at thermoneutrality (TN) during incubator care, at TN during SSC, and at elevated temperature (ET) during incubator care. Core temperature was measured via a rectal probe. Recordings were analyzed for the summed rate of bradycardia and desaturation (heart rate <2/3 of baseline; SpO 2 RESULTS: Rectal temperature remained unchanged during SSC and increased by 0.6 degrees C during ET ( P < .001). The summed rate of bradycardia and desaturation was increased during SSC but not during ET (TN: median 2.2/hour (range, 0-19), ET: median 1.7/hour (range, 0-13), SSC: 3.0/hour (0-25), P < .02 SSC vs ET).
CONCLUSION: Bradycardia and desaturation were increased during SSC, even at constant rectal temperature, whereas ET had no effect on these events. Moderate hyperthermia did not increase respiratory instability in preterm infants.

PMID 15480374  J Pediatr. 2004 Oct;145(4):499-502. doi: 10.1016/j.jped・・・
著者: K Heimann, P Vaessen, T Peschgens, S Stanzel, T G Wenzl, T Orlikowsky
雑誌名: Neonatology. 2010 Jun;97(4):311-7. doi: 10.1159/000255163. Epub 2009 Nov 4.
Abstract/Text BACKGROUND: Skin to skin care (SSC), prone (PP) and supine (SP) positions are standard positions in daily care for premature infants. Their influence on cardiorespiratory parameters and thermoregulation is discussed controversially.
OBJECTIVES: We compared SSC with PP, the recommended position for preterm infants, and SP, the safest position for term infants, and tested the hypothesis that SSC has no impact on cardiorespiratory parameters and thermoregulation.
METHODS: In 18 spontaneously breathing premature infants [median gestational 28 weeks (24-32); chronological age 36 days (7-64), and weight 1,543 g (750-2,100)], heart and respiratory rate, breathing pattern, episodes of desaturation (<85 but >or=80 and <80%), oxygen saturation and rectal temperature were analyzed with polygraphy (Alice 3(R) and 3.5(R)) in a 6-hour measuring cycle of three subsequent series (120 min each in SP, SSC and PP) and compared (Wilcoxon test).
RESULTS: During SSC, we found no increase in apneic attacks and bradycardic episodes and no difference in respiratory rate, breathing pattern, oxygen saturation, episodes and duration of desaturation compared to SP and PP. Episodes of desaturation <85 but >or=80 and <80% were more frequent in SP compared to PP (p = 0.0421 and p = 0.0319). Heart rate increased in SSC and PP compared to SP (154.86 bpm, SD 11.55, and 153.33 bpm, SD 15.95 vs. 150.25 bpm, SD 14.64; p = 0.0013 and p = 0.0346). Temperature level was not significantly higher during SSC and PP compared to SP except a rise between the start and the end of the 6-hour measuring cycle (37.05 degrees C, SD 0.2 vs. 37.30 degrees C, SD 0.3; p = 0.0436).
CONCLUSION: We found no significant SSC-mediated changes in quality and quantity of desaturations and in body temperature compared to PP in preterm infants.

Copyright 2009 S. Karger AG, Basel.
PMID 19887862  Neonatology. 2010 Jun;97(4):311-7. doi: 10.1159/0002551・・・
著者: D Millar, H Kirpalani
雑誌名: Indian Pediatr. 2004 Oct;41(10):1008-17.
Abstract/Text Mechanical ventilation of the newborn infant has increased neonatal survival. However, this increased survival has come at the expense of increased morbidity, in the form of bronchopulmonary dysplasia, and at the cost of an expensive technology. Continuous positive airway pressure (CPAP) is accepted as conferring clinical benefit in supporting the recently extubated preterm infant and in the management of apnea of prematurity. Attention is now being drawn to physiologic and clinical evidence to support CPAP use, with or without early surfactant, as a primary treatment of hyaline membrane disease. The purpose of this review is to explore these proposed benefits of non invasive ventilation and place them in the context of current clinical evidence.

PMID 15523126  Indian Pediatr. 2004 Oct;41(10):1008-17.
著者: Bettina Bohnhorst, Kathrin Cech, Corinna Peter, Michael Doerdelmann
雑誌名: Neonatology. 2010;98(2):143-9. doi: 10.1159/000279617. Epub 2010 Mar 16.
Abstract/Text BACKGROUND: Raised upper airway resistance may be involved in apnea of prematurity (AOP).
OBJECTIVES: To determine the effects of an oral versus a nasal gastric tube on episodes of hypoxemia and bradycardia in infants with AOP.
METHODS: In a randomized controlled cross-over trial, 32 infants (median gestational age 29 (range 24-31) weeks, postmenstrual age at study 32 (range 30-35) weeks) with the need for tube feeding and symptoms of AOP underwent a 24-hour recording of breathing movements, nasal airflow, heart rate, pulse oximeter saturation and pulse waveforms. A 5-Fr feeding tube was placed orally or nasally for 12 h each, the position selected first was randomly assigned. When the feeding tube was placed nasally, always the smaller nostril was selected. Each infant acted as his/her own control. Recordings were analyzed for the summed rate of bradycardia and desaturation (heart rate <2/3 of baseline, saturation RESULTS: The route of placing the feeding tube had no significant effect on the summed rate of bradycardia and desaturation (nasal route: median 1.6, CI 0.8-1.9; oral route: median 1.0, CI 0.9-1.6, p = 0.25).
CONCLUSION: We could not confirm an advantage of placing a feeding tube orally in these infants with AOP, as the oral route did not improve their symptoms of AOP. Possible explanations include: (i) the increase in nasal airway resistance by the 5-Fr nasogastric tube, inserted into the smaller nostril, is too small to have any effect on AOP; (ii) any benefit of the oral route is neutralized by the negative effects of an enhanced vagal stimulation, or (iii) study duration was too short to detect a difference in AOP.

Copyright 2010 S. Karger AG, Basel.
PMID 20234138  Neonatology. 2010;98(2):143-9. doi: 10.1159/000279617. ・・・
著者: B Lemyre, P G Davis, A G de Paoli
雑誌名: Cochrane Database Syst Rev. 2002;(1):CD002272. doi: 10.1002/14651858.CD002272.
Abstract/Text BACKGROUND: Apnea of prematurity is almost universal in infants who are born before 34 weeks gestation. Previous randomised trials and systematic reviews have found methylxanthines to be effective in preventing apnea of prematurity. However, recent concerns about potential long term side effects of methylxanthines on the neurodevelopment of low birth weight infants have led to an increased interest in alternate methods of treating apnea of prematurity. Nasal continuous positive airway pressure (NCPAP) is a useful method of respiratory support which reduces the incidence of obstructive or mixed apnea. However, apneic infants managed with NCPAP, with or without methylxanthines, sometimes require endotracheal intubation with its attendant morbidity and cost. Nasal intermittent positive pressure ventilation (NIPPV) is a simple, effective mode of respiratory support for older children and adults. It has been used to treat apnea in preterm infants but case reports of gastrointestinal perforations have limited its widespread use.
OBJECTIVES: In preterm infants with recurrent apnea, does treatment with NIPPV lead to a greater reduction in apnea and need for intubation and mechanical ventilation, as compared with treatment with NCPAP? Does NIPPV increase the incidence of gastrointestinal complications, i.e. gastric distension leading to cessation of feeds, or perforation?
SEARCH STRATEGY: MEDLINE was searched (1966-Oct week 2, 2001). Other sources included the Cochrane Controlled Trials Register (Cochrane Library, Disk Issue 3, 2001) and CINAHL (1982-Sept week 4, 2001). Also used were expert informants, previous reviews including cross-references, and conference and symposia proceedings.
SELECTION CRITERIA: All randomised and quasi-randomised trials were included. Participants included unventilated preterm infants experiencing apnea of prematurity. Interventions compared were intermittent positive pressure ventilation administered via the nasal route, either by short nasal prongs or nasopharyngeal tube, and nasal CPAP delivered by the same methods. Types of outcome measures: - failure of therapy as defined by apnea that is frequent or severe requiring additional ventilatory support - rates of endotracheal intubation - rates of apnea and bradycardia expressed as events per hour - gastrointestinal complications i.e. abdominal distension requiring cessation of feeds, or GI perforation
DATA COLLECTION AND ANALYSIS: Data were extracted independently by the three reviewers. The trials were analysed using relative risk (RR), risk difference (RD) and number needed to treat (NNT) for dichotomous data; means and weighted mean difference (WMD) were used for continuous data.
MAIN RESULTS: Two trials, enrolling 54 infants in total, fulfilled the inclusion criteria. Both reported only the short term results (4 to 6 hours) of the interventions. Only one infant (randomised to NCPAP) required intubation during this period. Ryan (1989), in a cross over study of 20 infants, showed no significant difference in rates of apnea (events/hr) between the 2 interventions [WMD -0.10 (-0.53,0.33)]. Lin (1998) randomised 34 infants and demonstrated a greater reduction in frequency of apneas (events/hr) with NIPPV compared to NCPAP [WMD -1.19 (-2.31,-0.07)]. Meta-analysis of both trials showed no difference in pCO2 (mmHg) at the end of the 4-6 hour study period [WMD 0.95 (-3.05,4.94)]. No data were reported on gastrointestinal complications.
REVIEWER'S CONCLUSIONS: Implications for practice: NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea that is frequent or severe. Its use appears to reduce the frequency of apneas more effectively than NCPAP. Additional safety and efficacy data are required before recommending NIPPV as standard therapy for apnea. Implications for research: Future trials with sufficient power should assess the efficacy (reduction in failure of therapy) and safety (GI complications) of NIPPV. Outcomes should be assessed throughout the entire period during which the infant requires assisted ventilation. The recent ability to synchronise NIPPV with an infant's spontaneous respirations is a promising development requiring further assessment.

PMID 11869635  Cochrane Database Syst Rev. 2002;(1):CD002272. doi: 10.・・・
著者: T Pantalitschka, J Sievers, M S Urschitz, T Herberts, C Reher, C F Poets
雑誌名: Arch Dis Child Fetal Neonatal Ed. 2009 Jul;94(4):F245-8. doi: 10.1136/adc.2008.148981. Epub 2009 Jan 8.
Abstract/Text BACKGROUND: Apnoea of prematurity (AOP) is a common problem in preterm infants which can be treated with various modes of nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV). It is not known which mode of NCPAP or NIPPV is most effective for AOP.
OBJECTIVE: To assess the effect of four NCPAP/NIPPV systems on the rate of bradycardias and desaturation events in very low birthweight infants.
METHODS: Sixteen infants (mean gestational age at time of study 31 weeks, 10 males) with AOP were enrolled in a randomised controlled trial with a crossover design. The infants were allocated to receive nasal pressure support using four different modes for 6 h each: NIPPV via a conventional ventilator, NIPPV and NCPAP via a variable flow device, and NCPAP delivered via a constant flow underwater bubble system. The primary outcome was the cumulative event rate of bradycardias (< or =80 beats per minute) and desaturation events (< or =80% arterial oxygen saturation), which was obtained from cardio-respiratory recordings.
RESULTS: The median event rate was 6.7 per hour with the conventional ventilator in NIPPV mode, and 2.8 and 4.4 per hour with the variable flow device in NCPAP and NIPPV mode, respectively (p value<0.03 for both compared to NIPPV/conventional ventilator). There was no significant difference between the NIPPV/conventional ventilator and the underwater bubble system.
CONCLUSION: A variable flow NCPAP device may be more effective in treating AOP in preterm infants than a conventional ventilator in NIPPV mode. It remains unclear whether synchronised NIPPV would be even more effective.

PMID 19131432  Arch Dis Child Fetal Neonatal Ed. 2009 Jul;94(4):F245-8・・・
著者: Barbara Schmidt, Robin S Roberts, Peter Davis, Lex W Doyle, Keith J Barrington, Arne Ohlsson, Alfonso Solimano, Win Tin, Caffeine for Apnea of Prematurity Trial Group
雑誌名: N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
Abstract/Text BACKGROUND: Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight.
METHODS: We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. We evaluated the short-term outcomes before the first discharge home.
RESULTS: Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups.
CONCLUSIONS: Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.).

Copyright 2006 Massachusetts Medical Society.
PMID 16707748  N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056・・・
著者: Barbara Schmidt, Robin S Roberts, Peter Davis, Lex W Doyle, Keith J Barrington, Arne Ohlsson, Alfonso Solimano, Win Tin, Caffeine for Apnea of Prematurity Trial Group
雑誌名: N Engl J Med. 2007 Nov 8;357(19):1893-902. doi: 10.1056/NEJMoa073679.
Abstract/Text BACKGROUND: Methylxanthine therapy is commonly used for apnea of prematurity but in the absence of adequate data on its efficacy and safety. It is uncertain whether methylxanthines have long-term effects on neurodevelopment and growth.
METHODS: We randomly assigned 2006 infants with birth weights of 500 to 1250 g to receive either caffeine or placebo until therapy for apnea of prematurity was no longer needed. The primary outcome was a composite of death, cerebral palsy, cognitive delay (defined as a Mental Development Index score of <85 on the Bayley Scales of Infant Development), deafness, or blindness at a corrected age of 18 to 21 months.
RESULTS: Of the 937 infants assigned to caffeine for whom adequate data on the primary outcome were available, 377 (40.2%) died or survived with a neurodevelopmental disability, as compared with 431 of the 932 infants (46.2%) assigned to placebo for whom adequate data on the primary outcome were available (odds ratio adjusted for center, 0.77; 95% confidence interval [CI], 0.64 to 0.93; P=0.008). Treatment with caffeine as compared with placebo reduced the incidence of cerebral palsy (4.4% vs. 7.3%; adjusted odds ratio, 0.58; 95% CI, 0.39 to 0.87; P=0.009) and of cognitive delay (33.8% vs. 38.3%; adjusted odds ratio, 0.81; 95% CI, 0.66 to 0.99; P=0.04). The rates of death, deafness, and blindness and the mean percentiles for height, weight, and head circumference at follow-up did not differ significantly between the two groups.
CONCLUSIONS: Caffeine therapy for apnea of prematurity improves the rate of survival without neurodevelopmental disability at 18 to 21 months in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312 [ClinicalTrials.gov].).

Copyright 2007 Massachusetts Medical Society.
PMID 17989382  N Engl J Med. 2007 Nov 8;357(19):1893-902. doi: 10.1056・・・
著者: M B Tracy, J Klimek, M Hinder, G Ponnampalam, S K Tracy
雑誌名: Acta Paediatr. 2010 Sep;99(9):1319-23. doi: 10.1111/j.1651-2227.2010.01828.x.
Abstract/Text AIM: The aim of the study is to assess the effects of an intravenous 10 mg/kg loading dose of caffeine base in cerebral oxygenation, cerebral Doppler blood flow velocity and cardiac output in preterm infants.
METHODS: Preterm neonates <34 weeks gestation were investigated at 1 and 4 h following the loading dose of caffeine using Doppler cerebral sonography, cardiac echocardiography and cerebral spatially resolved near-infrared spectroscopy.
RESULTS: Forty infants were studied with a mean gestational age (mean ± standard deviation) of 27.7 (±2.5) weeks, birth weight of 1155 (±431) g and a postnatal age of 2.8 (±2.2) days. Mean Anterior Cerebral Artery peak and time average mean blood flow velocity fell significantly by 14% and 17.7%, respectively at 1 h post-caffeine loading dose, which recovered partially by 4 h. Cerebral Tissue Oxygenation Index fell from pre-dose levels by 9.5% at 1 h with partial recovery to 4.9% reduced at 4 h post-dose. There were no significant changes in left or right ventricular output, transcutaneous oxygen saturation, transcutaneous PCO(2) or total vascular resistance.
CONCLUSIONS: A loading dose of 10 mg/kg caffeine base resulted in significant reduction at 1 h post-dose in cerebral oxygenation and cerebral blood flow velocity with partial recovery at 4 h.

© 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.
PMID 20412101  Acta Paediatr. 2010 Sep;99(9):1319-23. doi: 10.1111/j.1・・・
著者: Saif Al-Saif, Ruben Alvaro, Juri Manfreda, Kim Kwiatkowski, Don Cates, Mansour Qurashi, Henrique Rigatto
雑誌名: J Pediatr. 2008 Oct;153(4):513-8. doi: 10.1016/j.jpeds.2008.04.025. Epub 2008 Jun 4.
Abstract/Text OBJECTIVE: To determine whether inhalation of 0.8% CO(2) in preterm infants decreases the duration and rate of apnea as effectively as or better than theophylline with fewer adverse side effects.
STUDY DESIGN: A prospective, randomized, control study of 42 preterm infants of gestational age 27 to 32 weeks assigned to receive inhaled CO(2) (n = 21) or theophylline (n = 21). The study group had a mean (+/- standard error of the mean) birth weight of 1437 +/- 57 g, gestational age of 29.4 +/- 0.3 weeks, and postnatal age of 43 +/- 4 days. After a control period, 0.8% CO(2) or theophylline was given for 2 hours, followed by a recovery period.
RESULTS: In the CO(2) group, apneic time and rate decreased significantly, from 9.4 +/- 1.6 seconds/minute and 94 +/- 15 apneic episodes/hour to 3.0 +/- 0.5 seconds/minute and 34 +/- 5 apneic episodes/hour. In the theophylline group, apneic time and rate decreased significantly, from 8 +/- 1 seconds/minute and 80 +/- 8 apneic episodes/hour to 2.5 +/- 0.4 seconds/minute and 28 +/- 3 apneic episodes/hour. Cerebral blood flow velocity (CBFV) decreased only during theophylline administration.
CONCLUSIONS: Our findings suggest that inhaled low (0.8%) CO(2) concentrations in preterm infants is at least as effective as theophylline in decreasing the duration and number of apneic episodes, has fewer side effects, and causes no changes in CBFV. We speculate that CO(2) may be a better treatment for apnea of prematurity than methylxanthines.

PMID 18534618  J Pediatr. 2008 Oct;153(4):513-8. doi: 10.1016/j.jpeds.・・・
著者: Edward F Bell, Ronald G Strauss, John A Widness, Larry T Mahoney, Donald M Mock, Victoria J Seward, Gretchen A Cress, Karen J Johnson, Irma J Kromer, M Bridget Zimmerman
雑誌名: Pediatrics. 2005 Jun;115(6):1685-91. doi: 10.1542/peds.2004-1884.
Abstract/Text OBJECTIVE: Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences.
DESIGN, SETTING, AND PATIENTS: We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion.
INTERVENTION: The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status.
MAIN OUTCOME MEASURES: We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes.
RESULTS: Infants in the liberal-transfusion group received more RBC transfusions (5.2 +/- 4.5 [mean +/- SD] vs 3.3 +/- 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 +/- 2.5 vs 2.2 +/- 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes.
CONCLUSIONS: Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.

PMID 15930233  Pediatrics. 2005 Jun;115(6):1685-91. doi: 10.1542/peds.・・・
著者: Olga A Valieva, Thomas P Strandjord, Dennis E Mayock, Sandra E Juul
雑誌名: J Pediatr. 2009 Sep;155(3):331-37.e1. doi: 10.1016/j.jpeds.2009.02.026.
Abstract/Text OBJECTIVES: To determine the risks and benefits associated with the transfusion of packed red blood cells (PRBCs) in extremely low birth weight (ELBW) infants. We hypothesized that when ELBW infants underwent transfusion with the University of Washington Neonatal Intensive Care Unit (NICU) 2006 guidelines, no clinical benefit would be discernible.
STUDY DESIGN: We conducted a retrospective chart review of all ELBW infants admitted to the NICU in 2006. Information on weight gain, apnea, heart rate, and respiratory support was collected for 2 days preceding, the day of, and 3 days after PRBC transfusion. The incidence, timing, and severity of complications of prematurity were documented.
RESULTS: Of the 60 ELBW infants admitted to the NICU in 2006, 78% received PRBC transfusions. Transfusions were not associated with improved weight gain, apnea, or ventilatory/oxygen needs. However, they were associated with increased risk of bronchopulmonary dysplasia, necrotizing enterocolitis, and diuretic use (P < .05). Transfusions correlated with phlebotomy losses, gestational age, and birth weight. No association was found between transfusions and sepsis, retinopathy of prematurity, or erythropoietin use.
CONCLUSIONS: When our 2006 PRBC transfusion guidelines were used, no identifiable clinical benefits were identified, but increased complications of prematurity were noted. New, more restrictive guidelines were developed as a result of this study.

PMID 19732577  J Pediatr. 2009 Sep;155(3):331-37.e1. doi: 10.1016/j.jp・・・
著者: Richard J Martin, Jalal M Abu-Shaweesh, Terry M Baird
雑誌名: Paediatr Respir Rev. 2004;5 Suppl A:S377-82. doi: 10.1016/s1526-0542(04)90067-x.
Abstract/Text
PMID 14980300  Paediatr Respir Rev. 2004;5 Suppl A:S377-82. doi: 10.10・・・
著者: V P Carnielli, G Verlato, F Benini, K Rossi, M Cavedagni, M Filippone, E Baraldi, F Zacchello
雑誌名: Arch Dis Child Fetal Neonatal Ed. 2000 Jul;83(1):F39-43. doi: 10.1136/fn.83.1.f39.
Abstract/Text BACKGROUND: Methylxanthines are often administered to preterm infants for the treatment of apnoea.
AIMS: To study the effects of theophylline on energy metabolism, physical activity, and lung mechanics in preterm infants.
METHODS: Indirect calorimetry was performed for six hours before and after administration of a bolus of theophylline (5 mg/kg) in 18 preterm infants while physical activity was recorded with a video camera. Lung mechanics measurements were performed at baseline and 12 and 24 hours after theophylline treatment.
RESULTS: Theophylline increased mean (SEM) energy expenditure by 15 (5) kJ/kg/day and augmented carbohydrate utilisation from 6.8 to 8.0 g/kg/day, but fat oxidation was unchanged. After theophylline treatment, preterm infants had faster respiration, lower transcutaneous CO2, and improved static respiratory compliance without increased physical activity.
CONCLUSIONS: A bolus of 5 mg/kg theophylline increased energy expenditure independently of physical activity, increased carbohydrate utilisation, and improved respiratory compliance. The increased energy expenditure could be detrimental to the growth of the preterm infant.

PMID 10873170  Arch Dis Child Fetal Neonatal Ed. 2000 Jul;83(1):F39-43・・・
著者: Carlo Dani, Giovanna Bertini, Marco Pezzati, Simone Pratesi, Luca Filippi, Michele Tronchin, Firmino F Rubaltelli
雑誌名: Biol Neonate. 2006;89(2):69-74. doi: 10.1159/000088287. Epub 2005 Sep 12.
Abstract/Text BACKGROUND: Doxapram is a respiratory stimulant widely used for the treatment of idiopathic apnea of prematurity, although it has been demonstrated that it can induce a transient decrease of cerebral blood flow and that isolated mental delay in infants weighing <1,250 g is associated with the total dosage and duration of doxapram therapy.
OBJECTIVES: To evaluate the effects of doxapram on cerebral hemodynamics in preterm infants using cerebral Doppler ultrasonography and near-infrared spectroscopy.
METHODS: Preterm infants who required treatment with doxapram for apnea of prematurity unresponsive to caffeine were treated with doxapram at an hourly dose of 0.5 mg x kg(-1).h(-1), followed by 1.5 and 2.5 mg x kg(-1).h(-1).
RESULTS: 20 preterm infants were studied. Doxapram induced a significant decrease of oxygenated hemoglobin (O(2)Hb) and cerebral intravascular oxygenation (HbD = O(2)Hb - HHb) and an increase of HHb and CtOx concentrations, while cerebral blood volume and cerebral blood flow velocity did not change.
CONCLUSIONS: Doxapram infusion induces the increase of cerebral oxygen consumption and requirement and the contemporary decrease of oxygen delivery probably mediated by a decrease of cerebral blood flow. Caution must be recommended in prescribing this drug for apnea of prematurity.

PMID 16158005  Biol Neonate. 2006;89(2):69-74. doi: 10.1159/000088287.・・・

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