兒童急性肺損傷、急性呼吸窘迫症候群處置回顧


  June 26, 2009 — 6月15日急症醫學期刊線上版回顧了兒童急性肺損傷(acute lung injury,ALI)與急性呼吸窘迫症候群(acute respiratory distress syndrome,ARDS)的處置。
  
  波士頓哈佛醫學院、兒童醫院、術中與疼痛醫學部門的Adrienne G. Randolph醫師寫道,ALI 以及比較嚴重的ARDS,都是相當有破壞性的肺部發炎異常,會造成低血氧與呼吸衰竭。成人ALI/ARDS的診斷、流行病學、病因與治療都有詳細的概論。需要聚焦在小孩的回顧,以點出孩童與成人在流行病學、診斷、預後之間的差異,並瞭解小兒ALI/ARDS處置的實證基礎。
  
  【ALI和ARDS診斷的準則】
  不論是成人或是孩童,ALI和ARDS通常是根據美國-歐洲共同會議(AECC)提出的準則進行診斷,使用四個臨床參數。這些參數包括:(1)急性發生,(2)嚴重動脈低血氧、對單純吸入氧氣無反應(ARDS之PaO2/FIO2比≦200 torr;壓力單位) [≦— kPa],ALI之PaO2/FIO2比≦300torr[≦ — kPa]),(3) 胸部X光顯示雙側浸潤、瀰漫性肺炎,以及(4)沒有左心房高壓。
  
  雖然ARDS的肺部組織學準則包括瀰漫性肺泡傷害之證據,但是很少建議ALI和ARDS的孩童進行肺切片。根據AECC準則診斷,且呼吸衰竭期間延長的孩童,需要機械式輔助呼吸10到16天,平均而言,整體死亡率為10%至40%。
  
  本次回顧的目標是藉由於PubMed搜尋臨床試驗、對搜尋得來的文獻與其他有關ALI/ARDS診斷與流行病學的研究進行評讀,提供醫師有關小兒ALI/ARDS處置的綜合資訊。
  
  成人和小孩之ALI/ARDS有共同的風險因素和病理生理學,以及感染,特別是下呼吸道,是最常見的。在孩童,ALI和ARDS與高發病率、高死亡率、高健康照護花費有關。報告估計美國每年有2,500至9,000名孩童發生ALI,其中有500至2,000人死亡。
  
  孩童ALI/ARDS的臨床試驗不容易進行,因為此一年齡層的發病率較低,且ALI/ARDS發生率相對較低。回顧作者因此在某一程度上需仰賴專意見。
  
  【建議的介入方式】
  專家建議以下的介入方式:
  1. 應避免潮氣容積超過每公斤體重10-mL/kg。
  2. 建議的呼吸參數為,高原壓小於30 cm H2O、動脈pH值7.35- 7.45、PaO2值60至80torr(—至— kPa; SpO2 > 90%)。
  3. 輔助藥物治療應包括鎮靜、止痛藥物,預防壓力性潰瘍。
  4. 因為休克或完全低血氧而不穩定的病患,建議以血色素值10-g/dL為判斷是否需要輸血的臨界點。一旦休克或完全低血氧獲得緩解,文獻證據支持將判斷是否需要輸血的臨界點降低為7 g/dL。
  
  Randolph醫師寫道,未治療的感染、組織壞死、胰臟炎、與其他可能誘發發炎的反應,都會造成難以避免的ARDS。辨識ARDS的發生源且對其加以控制,對於獲得適當的臨床結果是重要的。因為敗血症是引發ALI的主因,建議在這些疑似感染的病患及早進行抗生素治療。
  
  【其他可能的治療】
  對於ALI/ARDS孩童,並無有關開始氣管插管和使用呼吸器的清楚指引,除非失去意識和無法保護呼吸道。當孩童需要插管時,必須由那些有為小孩插管之經驗者進行,使用適當大小的器械與氣管插管。當肺功能不佳時,使用有氣囊的氣管插管達成給予適當的呼氣末正壓。
  
  根據小兒試驗的證據,小兒ALI/ARDS的有效治療包括使用氣管內表面張力活性素;高頻振動空氣流通器;非侵犯式呼吸器;以及於復甦治療時,使用葉克膜治療。
  
  成人研究的證據認為,使用皮質類固醇治療肺發炎和纖維化,使用4-6 mL/kg 的潮氣容積、限制液體之管理也有幫助。不過,小孩只有從敗血性休克適當恢復之後才需要限制液體。
  
  造血幹細胞移植之後發生呼吸衰竭和ALI/ARDS的成人與小孩病患,死亡率在75%以上。可以利大於弊的介入方式包括連續靜脈血液過濾、支氣管肺泡灌洗術、etanercept這項藥物,和/或於某些特定案例進行肺部切片,以確認未診斷、但可治療的狀況。
  
  需後續研究方能建議用於ALI或ARDS的治療方式,包括俯臥、支氣管擴張劑治療、吸入式一氧化氮、嚴格的血糖控制、高流速鼻導管供應氧氣。
  
  兒童ALI/ARDS的治療目標,包括降低死亡率與發病率,加速恢復、適當的長期認知與呼吸功能。
  
  Randolph醫師結論表示,重點在使會造成細胞死亡與傷害到發育中腦部的完全低血氧程度最小化,使肺部與其他器官等次級損傷也最小化,以延長恢復。相較於成人,低血氧的嚴重度可以相當強地預測兒童ALI/ARDS的死亡率。多重器官衰竭也是兒童ALI/ARDS的死亡預測因子。
  
  Randolph醫師擔任Discovery Laboratories的顧問,且擔任lucinactant藥物臨床試驗的科學建議委員。
  
  Crit Care Med. 線上發表於2009年6月15日。
  
  

Acute Lung Injury, Acute Respiratory Distress Syndrome Management in Children Reviewed

By Laurie Barclay, MD
Medscape Medical News

June 26, 2009 — Management of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in children is reviewed in the June 15 Online First issue of Critical Care Medicine.

"...ALI and its more severe form,...ARDS, are devastating disorders of overwhelming pulmonary inflammation leading to hypoxemia and respiratory failure," write Adrienne G. Randolph, MD, MSc, from Perioperative and Pain Medicine, Children's Hospital and Harvard Medical School in Boston, Massachusetts. "There are detailed overviews of the diagnosis, epidemiology, pathogenesis, and treatment of adults with ALI/ARDS. This concise review is designed to focus on children, highlighting differences between children and adults in the epidemiology, diagnosis, prognosis, and evidence-base for management of pediatric ALI/ARDS."

Criteria for ALI and ARDS Diagnosis

Both in adults and in children, ALI and ARDS are most often diagnosed from criteria proposed by the American European Consensus Conference (AECC), with use of 4 clinical parameters. These parameters are (1) acute onset, (2) severe arterial hypoxemia not responding to use of inhaled oxygen alone (PaO2/FIO2 ratio ? 200 torr [? — kPa] for ARDS and PaO2/FIO2 ratio ? 300 torr [? — kPa] for ALI), (3) chest radiography showing bilateral infiltrates suggestive of diffuse pulmonary inflammation, and (4) absence of left atrial hypertension.

Although lung histology criteria for ARDS include evidence of diffuse alveolar damage, lung biopsy is seldom performed in children with ALI and ARDS. Children diagnosed by AECC criteria have prolonged duration of respiratory failure, requiring mechanical ventilation for 10 to 16 days, on average, and overall mortality rates are 10% to 40%.

The goal of this review was to offer clinicians a summary of the pertinent literature concerning pediatric management of ALI/ARDS by searching PubMed for clinical trials and performing a selected literature review of other relevant studies describing the epidemiology and diagnosis of ALI/ARDS.

Adults and children share common risk factors and pathophysiology of ALI/ARDS, with infection, particularly in the lower respiratory tract, being the most common trigger. In children, ALI and ARDS are associated with high morbidity rates, high death rates, and high healthcare costs. Reported population estimates suggest that the annual incidence of ALI in US children is 2500 to 9000, resulting in or contributing to 500 to 2000 deaths.

Clinical trials of ALI/ARDS are difficult to perform in children because of lower mortality rates as well as a relatively lower incidence of ALI/ARDS in this age group. The review author therefore relied, to some extent, on expert opinion.

Recommended Interventions

Expert opinion suggests that the following interventions be recommended:

1. Tidal volumes of more than 10-mL/kg body weight should be avoided.

2. Recommended ventilation parameters are plateau pressure of less than 30 centimeters H2O, arterial pH of 7.35 to 7.45, and PaO2 of 60 to 80 torr (— to — kPa; SpO2 > 90%).

3. Supplementary pharmacotherapy should include sedation, analgesia, and stress ulcer prophylaxis.

4. In patients who are unstable because of shock or profound hypoxia, a 10-g/dL hemoglobin threshold is recommended for packed red blood cell transfusion. Once profound hypoxia and shock have resolved, evidence supports lowering the hemoglobin transfusion threshold to 7 g/dL.

"Untreated infection, necrosis of tissue, pancreatitis, and other persistent triggers of the inflammatory cascade will lead to unrelenting escalation of ARDS," Dr. Randolph writes. "Identification of the ARDS trigger source and achievement of source control are essential to optimize clinical outcomes. Because sepsis is commonly the trigger for ALI, early antibiotic therapy is recommended in those suspected of being infected."

Other Possible Treatments

For children with ALI/ARDS, there are no clear guidelines for beginning endotracheal intubation and ventilator support, except for loss of consciousness and inability to protect the airway. When intubation is needed in children, this should be performed by those with sufficient experience in intubating children, using appropriately sized equipment and endotracheal tubes. Delivery of adequate positive end-expiratory pressure when pulmonary compliance is low may best be achieved with use of cuffed endotracheal tubes.

Based on evidence from pediatric trials, promising treatments of pediatric ALI/ARDS include use of endotracheal surfactant; high-frequency oscillatory ventilation; noninvasive ventilation; and, as a rescue treatment, use of extracorporeal membrane oxygenation therapy.

Evidence from adult studies suggests that use of corticosteroids to treat lung inflammation and fibrosis, use of 4- to 6-mL/kg tidal volumes, and restrictive fluid management may be helpful. However, fluids should only be restricted once children have recovered sufficiently from septic shock.

In adults and children with respiratory failure and ALI/ARDS after hematopoietic stem cell transplant, mortality rate is 75% or more. Interventions for which potential benefits may outweigh the risks include continuous venovenous hemofiltration, bronchoalveolar lavage, etanercept, and/or lung biopsy in selected cases to identify undiagnosed, treatable conditions.

Treatments that should be studied further before recommending their use in children with ALI or ARDS include prone positioning, bronchodilator therapy, inhaled nitric oxide, tight glycemic control, and oxygen delivered by high-flow nasal cannula.

Treatment goals for management of ALI/ARDS in children include reducing mortality and morbidity rates, hastening recovery, and optimizing long-term cognitive and respiratory function.

"It is important to minimize profound hypoxia that leads to cell death and is damaging to the developing brain, and to minimize secondary damage to the injured lung and other organ systems that could prolong recovery," Dr. Randolph concludes. "In contrast to adults, severity of hypoxia at presentation is a fairly strong predictor of mortality in children with ALI/ARDS....Multiple organ failure is also a consistent mortality predictor in children with ALI/ARDS."

Dr. Randolph has consulted for Discovery Laboratories and has also served as a scientific advisory board member for a clinical trial of lucinactant.

Crit Care Med. Published online June 15, 2009.

    
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