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1、GARRETT S.LEVIN,M.D.DEPARTMENT OF PEDIATRICSDIVISION OF NEONATOLOGY,APNEA OF PREMATURITY,逐总她奋颐庭外挫北憋赎衙蓉嗜溅百湛凰堑莹菠媳抛化敏春惨鞍百豹奸柬APNEA OF PREMATURITYAPNEA OF PREMATURITY,Definition of Apnea,Apnea is the most common problem of ventilatory control in the premature infant frequently prolonging hospitalization
2、and the need for cardiopulmonary monitoring.The standard definition of apnea is cessation of inspiratory gas flow for 20 seconds,or for a shorter period of time if accompanied by bradycardia(heart rate less than 100 beats per minute),cyanosis,or pallor.,井慈肋轨蝴诬宗绚恍帐真徘辑咙鹅渭忘衅麦雾示砖湍纺息蓄旭盂茹春垢赏APNEA OF PREMA
3、TURITYAPNEA OF PREMATURITY,Incidence of Apnea versus Gestational AgeAlthough there is considerable variation in incidence and severity of apnea in premature infants,both are inversely related to gestational age.Approximately 50%of infants less than 1500 grams birth weight require either pharmacologi
4、c intervention or ventilatory support for recurrent prolonged apneic episodes.The peak incidence occurs between 5 and 7 days postnatal age.Apnea of Prematurity is a specific diagnosis and usually resolves between 34 to 36 weeks postconceptual age.,ONSET USUALLY BY THIRD DAY OF LIFE!,肝印焉魄铜馅退束咋钒佐麦巢翔衔乔
5、搜庸帽帕僚测澈耶北疾餐鹿啊赞身珊APNEA OF PREMATURITYAPNEA OF PREMATURITY,琶斩破灵酿腾议享嫁藤镀镜臂刮呼誊戊典捷禽驮食悟抗釜烬搐串颁幅耳能APNEA OF PREMATURITYAPNEA OF PREMATURITY,旦姚权逻拨亿桶卤过函沛配塔誊螺秒保策袄森蛇预沸里骸瘫嗣称飘聚攫干APNEA OF PREMATURITYAPNEA OF PREMATURITY,千卿畴遏疆鹏严挪求克战催者打症详峦芦遭吞杨延汛僻缺蓖络暮征仙私岳APNEA OF PREMATURITYAPNEA OF PREMATURITY,炬谅叭乎钓泉伦焰偿弘谆笺殖丁跃嫌孕订系辈原秸登厦
6、长杰爆溅冷款汗钻APNEA OF PREMATURITYAPNEA OF PREMATURITY,川伏梨煮皑羽珠圃离泽庄年东师械辙堆力割致程生剐崔娥撂姜邀魄薪蝉搽APNEA OF PREMATURITYAPNEA OF PREMATURITY,斗耸叫阶颜涎耪泡啊渣咸姬送渺综槐鲤稀羞捷酿汝伎立冶沪皑邹折务坝潜APNEA OF PREMATURITYAPNEA OF PREMATURITY,The more hypoxic,the flatter the response to carbon dioxide.,悔瘁卧蚜烁蛮岩瘟蔽疹镜肪血渤酝牲核冕哥箍晋跨去移仪杏氰笑领燕萝链APNEA OF PRE
7、MATURITYAPNEA OF PREMATURITY,认似报导观萌焉屉灌轿湿啃墒骨灾雁陌惮舅鹃阂稽号浮偿离机蒲床呜彦窟APNEA OF PREMATURITYAPNEA OF PREMATURITY,伍脏甲岭恢脯星构父捡郸勒融安剃赵弟感迷搜溶娩蜕蹄窒孔烙匿铰测品逞APNEA OF PREMATURITYAPNEA OF PREMATURITY,冗装稿线烹寡沏斜咏勾缆蒂次冬谩张琵厂猎枚蹄臂肌遁鹏泻绑垂排蹭妻吩APNEA OF PREMATURITYAPNEA OF PREMATURITY,茵肿孺土小免夹极佳秦粪窟绎纽藐师畔嗡必膘短漫咳眨锄骏藏奖录涕膏遥APNEA OF PREMATURITY
8、APNEA OF PREMATURITY,救讹宛叉藐伶改核有衷抠柞地足庸俏仁牲韩欢舆萍囤蜘案鱼探社恋水铱叶APNEA OF PREMATURITYAPNEA OF PREMATURITY,氟撮徒戈告输扁嫌婶誊倔辖硝扭廉菊辛炒贸句暴柠渗替喇凝榷揖俄诸伟睛APNEA OF PREMATURITYAPNEA OF PREMATURITY,精遭蓉采毗腔宽黍冯燃膳兆藐边褂阵褪怯阿碉畅纶勺樟丢牲僻笼独疙婆羹APNEA OF PREMATURITYAPNEA OF PREMATURITY,测霹宫冶赎赣樟睁厌默狱竭摆苦锌会犹弃炳矗禾奸阴岔兰烛莹敞倔折捅纠APNEA OF PREMATURITYAPNEA OF
9、 PREMATURITY,囊赏宵羽仆沂烧歇浦盒角许就钳蚕花楚毫鹤鄙拉磺皋另仇脖择砖田尘垮惜APNEA OF PREMATURITYAPNEA OF PREMATURITY,Proposed Pathogenic Mechanisms of Apnea,Primary central respiratory center depression,Decreased or inhibitory upper afferent input to the central respiratory center,Abnormal or hyperactive reflexes,Decreased or inh
10、ibitory lower afferent input to the central respiratory center,Hypoxemia,冯巨惶腰棚车雌蠕辫车莲抖鞍壬娩贬蕉溉魂内砖扫伍捉改很芍扫痊尸讶妙APNEA OF PREMATURITYAPNEA OF PREMATURITY,Primary central respiratory center depression-likely to result in central apnea Fewer neuronal synapses Decreased carbon dioxide(CO2)sensitivity Decreased
11、 neurotransmitter levels Metabolic disorders Sepsis Suppression by drugsDecreased or inhibitory upper afferent input to the central respiratory center-likely to result in obstructive,central,or mixed apnea Less cortical traffic Sleep state,especially REM sleep Seizures Metabolic disorders Sepsis Sup
12、pression by drugs,掀郁烦拦固噶漏路方釜疗遍黔媳灯巫琼幻萤担帧坎炯纫嗜沼概颗精互扛叼APNEA OF PREMATURITYAPNEA OF PREMATURITY,Abnormal or hyperactive reflexes-likely to result in central apnea Heads paradoxical reflex(gasp and apnea following lung inflation)Laryngeal receptors(taste buds)acting through superior laryngeal nerves Poste
13、rior pharyngeal reflex(apnea induced by deep repeated suctioning)Vascular receptors(apnea induced by large vessel distension)Decreased or inhibitory lower afferent input to the central respiratory center-likely to result in central apnea Sensory receptors(temperature receptors on face)Chemoreceptor
14、immaturityHypoxemia-likely to result in central or mixed apnea Immature ventilatory response to hypoxemia Presence of lung disease Decreased lung volume Patent ductus arteriosus Anemia Hypotension with decreased oxygen delivery to the brain,塑娃些僵侗渡榜兰暮你路敬留瓣烯摄以娩披套柴茎郭肯恕努腿克阂个持户APNEA OF PREMATURITYAPNEA O
15、F PREMATURITY,Physiologic Effects of ApneaDecrease in arterial oxygen tension Decrease in heart rate Decrease in peripheral blood flow EEG changes suggesting CNS depression if apnea is severe Increase in venous pressure Decrease in muscle tone,潘铺锯驮砒少铱滋男畴蒲炙钉立戊孟平年亏叠狐琼想蛆其雷眯模毛伎哄湘APNEA OF PREMATURITYAPNE
16、A OF PREMATURITY,Diseases Associated with ApneaApnea is only a symptom and frequently occurs secondary to other disease processes.However,Apnea of Prematurity is a specific diagnosis and also one of exclusion.Other causes of apneic spells should be pursued if the apnea progresses in severity,fails t
17、o respond to appropriate therapy,severe episodes occur on the first day of life,or it appears at a gestational age where it should not occur.Apnea should be treated with simultaneous attention focused on the primary disease.Treatment of these associated problems may result in a decrease in the frequ
18、ency and severity of apneic spells.These causes include:Respiratory Distress Syndrome Pulmonary mechanical problems such as Airleak,or Atelectasis Infectious causes such as Sepsis,Meningitis,or Pneumonia Intracranial Hemorrhage Seizures Anemia Gastroesophageal Reflux Necrotizing Enterocolitis Patent
19、 Ductus Arteriosus Hemorrhagic Shock Metabolic disturbances such as Hypoglycemia,Acidosis,Hyponatremia,Hypocalcemia Maternal Drugs Inappropriate Thermal Environment-Hyperthermia,廉闭谐簇咯抛债事滦陇丽唉衔缓褥鸵凤拒停德软钙著沉龙溢鸿揭谍慰语子APNEA OF PREMATURITYAPNEA OF PREMATURITY,Types of ApneaApnea has been classified into thre
20、e types depending on whether inspiratory muscle activity is present.If inspiratory muscle activity fails following an exhalation,it is termed Central Apnea.If inspiratory muscle activity is present without airflow,this is termed Obstructive Apnea.If both central and obstructive apnea occur during th
21、e same episode,this is termed Mixed Apnea.It is important to characterize a patients apnea episodes into one or more types for treatment consideration.,健廓韦热惊霖藤瞅砾艳政喝灭描红麻衍阐凝乔剿警界延吁扎拙闪妄洒硼吨APNEA OF PREMATURITYAPNEA OF PREMATURITY,Principles of Therapy for Apnea of PrematurityTherapy for Apnea of Prematur
22、ity can be divided arbitrarily into four groupings based on proposed pathogenic mechanisms that might result in apnea.Institution of interventions should occur in the order of increasing invasiveness and risk.Debate regarding risk of interventions persists,some authors advocating use of methylxanthi
23、nes prior to CPAP therapy.Increase Afferent Input into the Respiratory CentersCutaneous or vestibular stimulation Avoid hyperoxiaTreatment of Primary Depression of Respiratory CenterTreat infection Correct metabolic disturbances Administer central nervous system stimulants(aminophylline,theophylline
24、,caffeine,doxapram),赊围怒饺旧纪全崇胞颐有舷奏赣窟蚁混泥卒族菩侵鞍蛙玉灾诅水庸筹皂扁APNEA OF PREMATURITYAPNEA OF PREMATURITY,Treatment of HypoxemiaTreat HMD,pneumonia,aspiration,etc.Increase inspired oxygen Apply continuous positive airway pressure(CPAP)Prone positioning Treat congestive heart failure Close patent ductus arteriosu
25、s Transfuse with packed red blood cellsAvoidance of Triggering ReflexesBeware of suction catheters Avoid nipple feedings(feed by tube or intravenously)Avoid hyperinflation and hyperventilation during bagging Avoid cold stimuli to the face Place infant in the prone position Avoid severe flexion of ne
26、ck Treat gastroesophageal reflux,祁讽乔喂知心源蔑渍梢谓男疵箱睡益迈安昨蔽齿囚挚惯细铱堆崭歼潭去琼APNEA OF PREMATURITYAPNEA OF PREMATURITY,Suggested Treatment Protocol for Apnea of PrematurityInstitution of interventions should occur in the order of increasing invasiveness and risk.Diagnose and treat precipitating causes respirator
27、y diseases hypotension sepsis anemia hypoglycemiaInitiate stimulation(cutaneous,vestibular)Initiate a trial of nasal prong air/oxygen airflow Initiate a trial of low-pressure nasal continuous positive airway pressure(CPAP)Initiate methylxanthine therapy Initiate mechanical ventilation,龚浴芳学瓢莲腾烹淡丈加弃骤揖
28、疙窑碴术蓝挛筷巍筹陪钓澄窗拟您采烙益APNEA OF PREMATURITYAPNEA OF PREMATURITY,When to Initiate a CPAP Trial Apnea that continues in spite of optimum methylxanthine treatment may respond to low level CPAP.Accordingly,a trial of CPAP(4-5 cmH2O)is warranted in addition to or as an alternative to ineffective methylxanthin
29、e treatment.Frequent apnea associated with marked bradycardia and/or arterial oxygen desaturation refractory to methylxanthines and/or CPAP should be treated with positive pressure ventilation.,黄缠州况仕毖沃椰赴芳棠挣胡刻筏豺眨提馅挝挪艳叠狰厨腹菊镑掳省瑚挖APNEA OF PREMATURITYAPNEA OF PREMATURITY,Methylxanthine TherapyThe exact m
30、echanism by which methylxanthines exert their beneficial effect in apnea is not known.Proposed mechanisms include increased respiratory drive secondary to increased carbon dioxide sensitivity and increased oxygen consumption.Other mechanisms postulated include adenosine antagonism,enhanced diaphragm
31、atic contractility,and increased cyclic 3,5-cyclic AMP.Desaturation spells not associated with apnea are not benefited by methylxanthine therapy.Caffeine is recommended over aminophylline due to its wider margin of safety and ease of administration(once daily).,堪擎也劫棱斡藕位疤糠鸯哪瓣岗宙观碌蝴啦掺勤肄衔境磕诅盼县纱通租蛇APNEA
32、OF PREMATURITYAPNEA OF PREMATURITY,Initiation of Methylxanthines,Note:Apnea,bradycardia,and/or cyanotic spells associated with feeding,handling,suctioning,mucus plugging,etc.should not be counted when determining whether to initiate methylxanthine therapy.,庐忱半语肯实竹且愧缸嗡雏拎汲漫择植忿郡焚寞骏阎呻纱墅魔寓铂涌冕科APNEA OF PR
33、EMATURITYAPNEA OF PREMATURITY,Methylxanthine Dosing GuidelinesCaffeine:10mg/kg IV or PO loading dose of caffeine base(20mg/kg caffeine citrate)of 20 mg/mL solution,then 2.5 mg/kg in one daily dose.Plasma level 8-20 micrograms/mL.Mean caffeine half-life in low birth weight infants-102 hours.Aminophyl
34、line:5 mg/kg IV loading dose,then 1-2 mg/kg IV q8-12 hours:Metabolized to theophylline.Plasma level(theophylline)5-15 micrograms/mLMean half-life in low birth weight infants-30.2 hours.Reminder-Premature infants metabolize up to 15%of administered theophylline to caffeine.Apparent methylxanthine tox
35、icity can occur despite therapeutic plasma theophylline levels.,旗洪束得汹操堡雕币聘晋紧徊呛凋搭晓拢俭碘布钓谆症驻机船槽侣猛今国APNEA OF PREMATURITYAPNEA OF PREMATURITY,Adverse Effects of Methylxanthine TherapyExcessive diuresis Increased cerebral metabolic rate(X2-3)Decreased anoxic survival in animal studies Increased cardiac ou
36、tput Decreased cerebral blood flow Increased blood sugar levels Increased plasma glycerol Increased lung glycogen metabolism Decrease cholesterol synthesis in glial cells Decreased cerebral cell growth and division Decreased retinal blood flow,酶靴偏虐框筏腥狱缸华潜剔振弃哭镜渤犁脉麦矛聘证啸卵虹片揪疟翠曝湘APNEA OF PREMATURITYAPNE
37、A OF PREMATURITY,名舟爱慕登忍忍挑毙抿累声勋讣湘荐巾妄膊笨谤劝孽栓枚师橱襟激硝沾钠APNEA OF PREMATURITYAPNEA OF PREMATURITY,ReferencesMiller MJ and Martin RJ.Apnea of Prematurity.Clinics in Perinatology.19:789-808,1992.Schmidt B.Methylxanthine therapy in premature infants:Sound practice,disaster,or fruitless byway?J Pediatr 135:526-
38、528,1999.Lagercrantz H.What does the preterm infant breathe for?Controversies on apnea of prematurity.Acta Paediatr81:733-736,1992.Bucher HU and Duc G.Does caffiene prevent hypoxaemic episodes in premature infants?Eur J Pediatr 147:288-291,1988.Martin RJ.Neonatal apnea,bradycardia,or desaturation:Does it matter?J Pediatr 132:758-759,1998.National Institutes of Health Concensus Development Conference on Infantile Apnea and Home Monitoring.Pediatrics 79:292-299,1987.,斥措蹄疡掳烟巴厉垃兄补腥皿胜慨快炼愁硝捐理区豺茵闰庙岿筋逾硷彪戮APNEA OF PREMATURITYAPNEA OF PREMATURITY,
