亚低温治疗缺氧缺血性脑病

准入条件
1 胎龄大于36周，生后6小时内进入亚 低温程序。 2 围生期窒息缺氧史。 3 5分钟Apgar小于6。 4 脐血或生后1小时内PH小于7。 5 生后需要通气支持超过10分钟。
排除标准
1 六小时内不能进行亚低温治疗。 2.严重先天畸形。 3 严重宫内发育迟缓出生体重小于1800
千克。 4 严重染色体缺陷病 5 ＜35周早产儿
• Moderate or severe HIE ~ 0.5 – 1 per 1000 live births
• Mortality ~ 10 - 60% • Morbidity ~ 25% of survivors There are no specific treatments proven
to decrease brain damage from HIE
consistent with diagnosis of moderate to severe HIE
CoolCap
• Intervention:
– Cooling Cap fitted to head for 72h
• Small thermostatic cooling unit with a pump to circulate water through the cap
缺氧缺血性脑病HIE
围生期窒息引起的部分或完全缺氧、脑血 流减少或暂停导致的胎儿、新生儿脑损伤
我国HIE发病率3-6‰，其中15-20%在新生 儿期死亡。 存活者中20-30%有不同程度神经系统后遗 症
HIE in Neonates
• Diagnostic criteria are vague
– Low Apgar scores at 5 mins – Change in consciousness – Signs of significant hypoperfusion (ie acidosis) – Requirement for ventilation – Seizures – Other
– Thoresen, 2000; 9 patients, both methods – non-hazardous cardiovascular changes noted, particularly with over-cooling or
– Shankaran, 2002; 19 patients, whole body cooling – no adverse effects
亚低温治疗缺氧缺血性脑病
目的 了解亚低温疗法的由来 明确亚低温治疗对缺血缺氧性脑病的 疗效 掌握我院亚低温疗法的方案
History of Therapeutic Hypothermia
• First scientific report was published in 1945 by Dr. Temple Fay
Pathophysiology of Brain Injury due
to Hypoxic-Ischemic Insult
• 2 phases of neuronal death
– Immediate
• “Primary neuronal death”
– cellular hypoxia with exhaustion of the cell’s high energy stores (primary energy failure)
• 呼吸机调节无特殊，三支ຫໍສະໝຸດ Baidu（血气、血糖 、血压），三对症同未用亚低温时
• 查血气时注意标注当时体温。
复温
– Latent (>6 hours)
• “Delayed neuronal death”
– Multiple mechanisms » Hyperemia 充血 » Cytotoxic edema 细胞毒性水肿 » Mitochondrial failure 线粒体·损伤 » Accumulation of excitotoxins 兴奋性氨基酸 » Active cell death » Nitric oxide synthesis NO失衡 » Free radical damage and cytotoxic actions of activated microglia
Copyright ©Radiological Society of North America, 2006
Pathophysiology of Brain Injury due to Hypoxic-Ischemic Insult
• Latent phase provides window of therapeutic intervention
• Recently this therapy has emerged as therapy for infants suffering HIE related to birth
Therapeutic Hypothermia in Babies
• Small human studies with encouraging results
– No other sources of warming provided during the cooling period
Whole-Body Hypothermia
• After 72 hours
– Set point of the cooling system was increased by 0.5°C per hour for six hours
– Esophageal probe was inserted
• Esophageal temperature was lowered to 33.5°C by the blanket's servomechanism
• Needed a second blanket as a thermal sink
• Initial water temperature 8° to 12°C • Radiant warmer, servo-controlled to abdominal
skin temperature, adjusted to maintain the rectal temperature at 34–35°C • Initially, warmer off for 20-30 mins to speed cooling
– Esophageal probe then removed – Thereafter, skin temperature was controlled
by the radiant warmer's servomechanism
• Warmer temp was set 0.5°C higher than the skin temperature and increased 0.5°C every hour until the set point of the warmer reached 36.5°C
– Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ
– Lancet. 2005 Feb 19-25;365(9460):663-70
– Seetha Shankaran, et al – N Engl J Med. 2005 Oct 13;353(15):1574-84
Whole-Body Hypothermia
Whole-Body Hypothermia
• Intervention
– Placed on an infant-size blanket precooled to 5°C
– Rewarmed < 0.5°C/h until temperature was normal
亚低温 33-34℃
CoolCap
CoolCap
CoolCap – Subgroup Analysis
Whole-Body Hypothermia
• Whole-Body Hypothermia for Neonates with Hypoxic–Ischemic Encephalopathy
注意事项
• 1 亚低温治疗时除尿片外全身裸露
• 2 亚低温治疗时患儿会表现为皮肤发绀和苍 白 氧饱和度报警值设在85%
• 3 必须保持血气，电解质平衡
• 亚低温治疗期间皮肤颜色为灰色或发暗， 如果血气氧饱和度正常可不予处理。
• 亚低温期间患儿心率会低于90bpm，心电 监护心率报警值设定为80bpm。
CoolCap
• Inclusion criteria:
– >35 weeks EGA – Apgar score ≤ 5 at 10 mins; or pH <7 or base
deficit >16 mmol/L within 60 mins of birth – Sarnat score and amplitude-integrated EEG
– Significant proportion of total injury
Figure 2. Patterns of brain injury in mild to moderate hypoperfusion
Chao, C. P. et al. Radiographics 2006;26:S159-S172
– “Observations on generalized refrigeration in cases of severe cerebral trauma”
– Also investigated use in cancer
HIE in Neonates
• Perinatal asphyxia ~ 3 – 5 per 1000 live births
Wagner, 2002 – Rats
Gunn, 1997 - Lambs
Tooley, 2003 – Piglets
Summary
• Multiple lines of evidence suggest therapeutic hypothermia may be neuroprotective
• 2 recent, randomized controlled trials of ~ 500 infants
– CoolCap – NICHD whole-body hypothermia
CoolCap
• Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial
Whole-Body Hypothermia
Whole-Body Hypothermia
Cochrane Review
Cochrane Review
Shah, Arch Pediatr Adolesc Med. 2007;161(10):951-958
Tooley, 2003 – Piglets
医嘱
1 特级护理 告病危
2多功能心电监护:心率维持在80-140 次/分，
3 监测SpO285-99%。
4 亚低温毯温度设置33-34摄氏度
监测
• 监测患儿体温Q15分钟×2-4小时，以后Q2 小时至低温疗法结束。
• 监测血糖Q8h×1day，Q12h×2day， Qd×4day，
• 血气分析Q1day， • 肝肾功能电解质Qd×3day， • 凝血相Qd×3day 。
– Gunn, 1998; 22 patients, head cooling – no adverse effects compared with control
– Azzopardi, 2000; 16 patients, whole body cooling – no adverse effects