- 學位論文
葉克膜於小兒病患及心肺復甦之應用
Extracorporeal membrane oxygenation (ECMO): Application for pediatric patients and for cardiopulmonary resuscitation
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摘要
ECMO原本用於新生兒肺部疾病引起的急性呼吸衰竭，因為ECMO的進步，任何病人需要暫時性心肺功能支持時，ECMO是一個可考慮的選擇。 在本院ECMO之臨床應用於成人機械循環輔助較早成功，病例數一直往上增加，並有相當文獻發表。但在小兒領域的成功率比不上成人。在本研究以前本院並無小兒葉克膜的文獻報導 因此我們嘗試擴展ECMO至小兒機械循環輔助的領域，以開創本院ECMO之小兒領域。研究目標主要分為下列幾項: 1. 心臟手術後以ECMO 支持心臟功能 心臟手術後初期，許多病患的心臟功能降低， 因此在其他傳統方式均無法使衰竭的心臟，維持適當的心輸出量時，使用ECMO，或許就能拯救生命，對本院心臟手術病人多一分保障。 1999 年 1 月至 2004 年 12 月間，在國立臺灣大學醫學院附設醫院接受心臟手共 2107 位病童於本院接受心臟手術，其中 68 位病童 (3.2%)術後 7 天內，使用 ECMO。本研究世代的整體存活率為 32.4%，而年齡與性別不影響存活率。有雙心室循環生理病童的存活率(41.3%)，高於接受體肺循環分流術或腔靜脈肺動脈吻合術的病童存活率(13.6%，p < 0.05)。使用 ECMO 期間發生急性腎衰竭與否，與死亡率顯著相關（發生急性腎衰竭：83%，未發生：33.5%，p < 0.001）。開始使用 ECMO的第 2 天至第 4 天，存活病童的最低乳酸濃度 (2.4mmol/L)，低於未存活病童 (3.3 mmol/L，p < 0.05)。最近的 2 年期間 (47.6%)，存活率高於前 4 年 (25.5%)，但此結果並未達統計顯著 (p = 0.07)。本試驗結論為，術後需使用 ECMO 輔助維持心臟功能的兒科病童中，非雙心室循環生理、發生急性腎衰竭、使用 ECMO 後乳酸血中濃度偏高等，死亡的風險均會增加。 在這第一部分的研究中，我們發現有些病患可以脫離ECMO但仍無法存活。因此我們進行下一部分的研究 2. 使用機械循環輔助系統的兒科病童，其血中 B 型排鈉利尿胜肽的臨床意義 研究背景：B 型排鈉利尿胜肽 (B-natriuretic peptide;BNP) 是診斷心臟衰竭的指標。心臟衰竭的成人患者，植入心室輔助器後，若 BNP 濃度下降，可能表示心臟復原，但對於使用機械維生系統的兒科病童，其 BNP 濃度的意義，仍相當不明瞭。 本研究旨在瞭解，在需使用葉克膜維生的兒科病童中，BNP 血中濃度所具的臨床訊息價值，及是否能預測預後。本研究收集 15 位發生心因性休克，而輔以體外循環維生系統（ECMO，葉克膜）的病童，於使用葉克膜前、中，及拔除葉克膜後，測量其 BNP 濃度。 研究結果：使用葉克膜前，所有受試病童的 BNP 濃度均升高（中位數：1,430 pg/mL，範圍：361 - 5,000 pg/mL）。本研究的 15 位受試病童中，有 1 位移植心臟，2 位停用葉克膜死亡，其餘 12 位拔除葉克膜，4 位受試病童一開始成功拔除，之後卻死亡。葉克膜拔除後一天，未存活病童的 BNP 濃度（中位數：3,685 pg/mL，範圍：2,494 - 5,000 pg/mL）高於存活病童（中位數：1,127 pg/mL，範圍：108 - 3,030 pg/mL，p = 0.016）。葉克膜拔除後第 4 天，存活病童的 BNP 濃度（中位數：498 pg/mL，範圍：108 - 890 pg/mL）低於未存活病童（中位數：3,900 pg/mL，範圍：3,230 - 5,000 pg/mL，p = 0.017）。但其他臨床變項如血壓、中央靜脈壓、排尿量等則未達統計顯著。 結論：使用葉克膜的受試病童中，存活病童的 BNP 濃度低於未存活病童。我們認為，BNP 的連續血中濃度，可針對使用機械循環輔助系統的病童做為監測指標。 3. 對院內心跳停止病童施予ECMO體外心肺復甦術 簡介 由於長時間施予 CPR 的存活率頗低，因此更積極的復甦方式，以改善存活率是研究重點。體外循環維生系統（葉克膜，ECMO）可將含氧血灌流至全身，因此能暫時輔助心肺功能。施予 CPR 時，同時使用ECMO的方式便稱為ECPR。然而，施予 ECPR 時，需要專業的外科及灌流技術，以及經驗豐富的團隊，也需要龐大的醫療資源。 因此我們針對這個題目研究是否能提供院內心跳停止病童施予體外心肺復甦術 (ECPR) 急救回這些病患。 研究方法： 接受體外循環維生系統（葉克膜，ECMO）心肺復甦術 (ECPR) 治療的兒科患者，均納入本試驗。試驗結果比較 3 個世代的受試病童 (1999-2001、2002-2005、2006-2009)，並分析存活率及神經預後。神經預後良好，定為小兒腦部功能分類 (PCPC) 為第 1、2、3 類。 研究結果： 我們1999 至 2009 年間共有54 件 ECPR，其出院的存活率為 46% (25/54)，21 位 (84%) 存活病童的神經預後良好。 存活病童中，施予心肺復甦術 (CPR) 的時間為 39+/-17 分鐘，未存活病童則為 52+/- 45 分鐘（p 值未達統計顯著 [p=NS]）。單純心臟病因造成心跳停止的受試病童 (47% [18/38]，存活率與非心臟病因的受試病童相近 (44% [7/16]，p=NS) 施予 ECPR 之前，未存活病童的乳酸血中濃度較高（未存活：13.4+/-6.4 mmol/L，存活：8.8+/-5.1 mmol/L，p < 0.01），施予 ECPR 之後，則未存活組發生腎衰竭的比例較高（未存活：66% [19/29]，存活：20% [5/25]，p < 0.01）。 相較於 1999 - 2002 年復甦的受試病童，2006 - 2009 年間復甦的受試病童，施予 CPR 的時間較短 (2006 - 2009 年：34+/-13 分，1999 - 2002 年：78+/- 76 分，p=0.032)，且存活率較高 (2006 - 2009 年：55% (16/29)，1999 - 2002 年：0% (0/8)，p=0.017)。結論：本院對院內心跳停止病童施予 ECPR 的十一年經驗中，近幾年 ECPR 的時間已見縮短，恢復情形也有所改善。施予 ECPR 前的乳酸濃度越高，而施予 ECPR 後發生腎衰竭，則死亡率越高。至於由非心臟病因造成的心跳停止，仍然可有成功 ECPR 的機會。
並列摘要
Extracorporeal membrane oxygenation (ECMO) had been quite successfully utilized in neonatal respiratory failure, but cardiac ECMO was used more and more in recent years. In National Taiwan University Hospital, we had successful experience in adult ECMO for mechanical circulatory support, however, there were no published paper in our pediatric group. The purpose of this study was to apply ECMO for pediatric mechanical circulatory support, and try to identify the prognostic factors. The first part of this study is ECMO for post-operative circulatory failure in pediatric patients. Between January 1999 and December 2004, 2107 children had cardiac surgery in our institute. There were sixty-eight pediatric patients (3.2%), who received ECMO within 7 days after cardiac surgery in our hospital. The overall survival rate of this cohort was 32.4%. The age and gender did not affect the survival. Patients with separate biventricular physiology had a higher probability of survival than those with systemic-pulmonary shunt or cavo-pulmonary anastomosis (41.3% vs 13.6%, p<0.05). Acute renal failure during ECMO were significantly associated with mortality (83% vs 33.5%, p<0.001). After ECMO initiation, the lowest lactate levels on the 2nd-4th day were lower in the survivors than in the non-survivors (2.4 vs 3.3 mmole/L, p<0.05). There was a trend toward a better survival in recent two years in comparison to the previous 4 years (47.6% vs 25.5%, p=0.07), although it did not reach statistical significance. In this study, non bi-ventricular physiology, acute renal failure, and high blood lactate levels after ECMO increased the risk of mortality for pediatric patients requiring ECMO for post-operative cardiac support. In this part of study, we found some patients could be separate from ECMO but died in the ICU, we try to study if B-type natriuretic peptide (BNP) could be served as a marker during pediatric ECMO support. In adult patients with heart failure, decreased BNP levels after implantation of ventricular assist devices might be indicative of recovery. However, BNP levels among pediatric patients receiving mechanical support are unknown. We included fifteen pediatric patients with cardiogenic shock who were supported by extracorporeal membrane oxygenation (ECMO). The BNP levels were determined before ECMO initiation, during ECMO support, and after ECMO removal. All patients had elevated BNP levels before initiation of ECMO (median, 1430 pg/mL; range, 361–5000 pg/mL). Among the 15 patients, one received heart transplantation. ECMO was withdrawn in two patients, and the other 12 patients were weaned from ECMO. Four patients died after initial successful weaning from ECMO. The BNP levels of the non-survivors (median, 3685 pg/mL; range, 2494–5000 pg/mL) were higher than that of the survivors (median, 1127pg/mL; range, 108–3030 pg/mL) on the next few days after ECMO removal (p = 0.018). The BNP levels on the 4th day after removal of ECMO among the survivors (median, 498 pg/mL; range, 108–890 pg/mL) were lower than that among the non-survivors (median, 3900 pg/mL; range, 3230–5000 pg/mL; P < 0.01). While the differences in BNP levels at these time points reached statistical significance, the other clinical parameters, such as blood pressure, central venous pressure, lactate level, and urine amount did not. In this art, we concluded that among pediatric patients supported with ECMO, the survivors had lower BNP levels than those who did not survive. We suggest that serial blood BNP levels could be potential markers for monitoring pediatric patients on mechanical circulatory support, and the concept merits further study. The third part of this study was to apply ECMO in pediatric cardiopulmonary resuscitation (CPR), this technique now was called as ECPR. Between 1999 and 2009, we performed 54 ECPR in pediatric in-hospital cardiac arrest. The survival rate to hospital discharge was 46% (25/54), and 21 (84%) of the survivors had favorable neurological outcomes. The duration of cardiopulmonary resuscitation (CPR) was 39+/-17 minutes in the survivors and 52+/- 45 minutes in the non-survivors (p=N.S). The patients with pure cardiac causes of cardiac arrest had a similar survival rate to those with non-cardiac causes(47%[18/38] vs 44%[7/16], p=NS) The non-survivors had higher serum lactate levels prior to ECPR (13.4+/-6.4 vs 8.8+/-5.1 mmol/L , p < 0.01) and more renal failure after ECPR (66% [19/29] vs 20% [5/25], p < 0.01). The patients resuscitated between 2006-2009 had shorter a shorter duration of CPR (34+/- 13min vs 78+/- 76 min, p=0.032), and higher rates of survival (55% (16/29) vs 0% (0/8), p=0.017) than those resuscitated between 1999-2002. In summary, during the 11-year experience with ECPR for pediatric in-hospital cardiac arrest, the duration of CPR has shortened and outcomes have improved in recent years. Higher pre-ECPR lactate levels and the presence of post-ECPR renal failure were associated with increased mortality. The presence of non-cardiac causes of cardiac arrest did not preclude successful ECPR outcomes.
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