Appendix J — 附錄 J: Ch05 OpenEvidence 一問一答

本附錄為 Ch05 章節的 OpenEvidence 實證驗證紀錄（10 題）。每題含：

  • Q：原設計問題（針對手冊特定敘述設計）
  • A：OE 綜合回答（整合多篇原始文獻）
  • Verdict：🟢 支持 / 🟡 修正 / 🟠 部分 / 🔴 推翻
  • Article ID：OpenEvidence session 識別碼
  • Top citations：Top 5 原始文獻（含 DOI 與 chip 代碼；📄 本機 PDF 由 chip drawer 開啟）

驗證日期：2026-04-21 狀態：10 / 10 完成（3 🟢 小修正 · 4 🟡 修正 · 3 🔴 推翻）

完整 metadata 見 qa/oe_papers_library/Ch05_surgery/Ch05_citations.json。

J.1 驗證記錄

J.1.1 Q35 [High] Ch05:50 Heparin 100 IU/kg, ACT ≈ 300 s

Q: In lung transplantation with intraoperative central VA-ECMO using heparin-coated circuits, is heparin 100 IU/kg with ACT target ~300 seconds superior to lower-dose 40-60 IU/kg without continuous ACT monitoring for preventing circuit thrombosis and reducing bleeding/PGD? Include contemporary evidence from Vienna or other high-volume LTx centers.

A (OE 綜合): Low-dose heparin (40-75 IU/kg) without continuous ACT monitoring appears superior to standard-dose heparin (100 IU/kg) with ACT targeting ~300 seconds for intraoperative central VA-ECMO during lung transplantation with heparin-coated circuits. Contemporary evidence demonstrates that low-dose protocols significantly reduce bleeding and transfusion requirements without increasing circuit thrombosis or primary graft dysfunction (PGD).

Evidence from High-Volume Centers

A 2024 study from Vienna (109 patients, 2020-2022) found that lower UFH doses for intraoperative central VA-ECMO reduced intraoperative blood product consumption and blood loss with no thrombotic complications related to the patient or ECMO circuit[8][21]. Lower doses also decreased the incidence of surgical revision for hemothorax[8][21].

A 2025 multicenter study (116 patients, 2016-2023) directly compared two protocols: low-dose (75 IU/kg at cannulation, no redosing, plus tranexamic acid) versus standard (ACT >180 seconds maintained with redosing and protamine reversal)[6][13]. The low-dose protocol demonstrated: - Dramatically reduced transfusion requirements: median 0 vs 4.37 units pRBCs (P<.001), 0 vs 2 units FFP (P<.001), 0 vs 1 unit platelets (P<.001), and 0 vs 9 total blood products (P<.001)[6][13] - Shorter surgical time (7.28 vs 8.53 hours, P<.001)[6][13] - No difference in grade 3 PGD at 72 hours (P=.42)[6][13] - Similar rates of DVT, airway dehiscence, pneumonia, and acute kidney injury[6][13]

Circuit Thrombosis Risk

Multiple studies confirm that low-dose heparin with modern heparin-coated circuits does not increase thrombotic complications. A meta-analysis of 7 studies (553 patients) comparing low versus standard anticoagulation for ECMO found similar rates of pulmonary embolism, intracardiac thrombus, and successful weaning, while significantly reducing gastrointestinal (OR 0.36, 95% CI 0.20-0.64) and surgical site hemorrhage (OR 0.43, 95% CI 0.20-0.94)[10].

The Vienna center also reported experience with LMWH versus UFH in 102 lung transplant patients on perioperative ECMO (2013-2017), finding that the UFH group had significantly higher thromboembolic events (50% vs 20%, P=.01) despite similar bleeding rates[12][24].

Guideline Recommendations

The ISHLT/HFSA 2023 guideline on acute mechanical circulatory support notes that while surface coatings (heparin, albumin, phosphorylcholine) aim to reduce activation, the ideal level of anticoagulation or monitoring targets are not defined[4][11]. Standard recommendations include 50-100 IU/kg bolus at cannulation, with ACT targets of 180-220 seconds or anti-Xa 0.3-0.7 IU/mL, but lower goals may be considered with high bleeding risk[4][11].

The AATS 2022 expert consensus document on mechanical circulatory support in lung transplantation suggests low or no heparin regimens for patients with significant adhesions and impaired coagulation status (Class 2a, Level C-EO)[25].

**Mon…

Verdict: 🟢 修正（但支持方向相反） — Low-dose 40-75 IU/kg 顯示優於 100 IU/kg（Vajter 2024、Chan 2025、AATS 2023）；手冊的 100 IU/kg ACT~300s 應改為 40-75 IU/kg ± 免 ACT（coated circuit + TXA）

Article ID: fc001eab-68f0-4a40-b192-c7e823c529e7

Top citations: - Vajter J, Holubova G, Novysedlak R, et al.. 2024 Transplant International. doi:10.3389/ti.2024.12752 [OE-Vajter-2024-VienaECMO] - Chan EG, Deitz RL, Ryan JP, et al.. 2025 J Thorac Cardiovasc Surg. doi:10.1016/j.jtcvs.2024.09.055 - Lv X, Deng M, Wang L, et al.. 2021 PloS One. doi:10.1371/journal.pone.0249854 [OE-Lv-2021-LowAnticoag] - Gratz J, Pausch A, Schaden E, et al.. 2020 Artificial Organs. doi:10.1111/aor.13642 [OE-Gratz-2020-LMWH] - Bernhardt AM, Copeland H, Deswal A, Gluck J, Givertz MM.. 2023 J Cardiac Failure. doi:10.1016/j.cardfail.2022.11.003 [OE-Bernhardt-2023-ISHLTMCS] - Hartwig M, van Berkel V, et al.. 2023 J Thorac Cardiovasc Surg. doi:10.1016/j.jtcvs.2022.06.024 [OE-AATS-2023-MCS-LTx] - Vajter J, Garaj M, Holubova G, et al.. 2026 ASAIO Journal. doi:10.1097/mat.0000000000002653 [OE-Vajter-2026-Viscoelastic] - Guglin M, Zucker MJ, Bazan VM, et al.. 2019 JACC. doi:10.1016/j.jacc.2018.11.038 [OE-Guglin-2019-VAECMO]

J.1.2 Q36 [Med] Ch05:70-72 Thoracotomy vs Clamshell

Q: In bilateral lung transplantation, does bilateral anterolateral thoracotomy vs clamshell incision reduce wound infection (9.7% vs 22.8%?) and improve 3-6 month FEV1 (82% vs 70%?)? Cite Vienna and other recent cohort evidence.

A (OE 綜合): Bilateral anterolateral thoracotomy does reduce wound complications and improve early pulmonary function compared to clamshell incision in bilateral lung transplantation, though the specific rates cited (9.7% vs 22.8% for wound infection; 82% vs 70% for FEV1) do not precisely match published cohort data.

Wound Complications

Recent cohort evidence demonstrates significantly fewer wound-related complications with bilateral anterolateral thoracotomy versus clamshell incision. A 2025 Dutch single-center study of 249 patients (132 anterolateral, 117 clamshell) found significantly less wound-related complications in the anterolateral group after multivariable adjustment[1]. An early Vienna study (Venuta et al. 2003) reported 0% wound complications (0/34 patients) with bilateral anterolateral thoracotomy versus 46% chest wall complications (17/37 patients) with clamshell, including sternal osteomyelitis requiring debridement (3 patients), Kirshner wire migration (3 patients), sternal override (3 patients), and prolonged pain (8 patients)[6].

A 2017 U.S. study found 0% major surgical site complications requiring operative intervention with median sternotomy versus 16.2% (11/68) with clamshell incision (p=0.01), with 3-year freedom from major complications of 100% versus 80% respectively[3]. A 2023 Korean study comparing sternum-sparing bilateral anterolateral thoracotomy (n=100) to clamshell (n=34) did not report specific wound infection rates but noted significantly shorter mechanical ventilation (11.4 vs 17.3 days, p=0.028) and ICU stay (15.0 vs 21.5 days, p=0.033)[2].

Pulmonary Function Outcomes

Multiple studies demonstrate superior FEV1 with sternum-sparing approaches. The Vienna group (Venuta et al. 2003) reported FEV1 at 3 weeks of 71±8% predicted with bilateral anterolateral thoracotomy versus 58±7% predicted with clamshell (p<0.05)[6]. A 2016 UK study (Harefield Hospital) found FEV1 at 6 months of 86±21% predicted with minimally invasive bilateral anterior thoracotomies versus 74±21% predicted with clamshell (p<0.01)[9]. A 2026 Korean VATS study showed FEV1 at 1 month of 85.8±18.0% predicted versus 67.3±22.6% predicted with clamshell (p<0.001), with differences persisting at 12 months[5].

An earlier Vienna study (Taghavi et al. 1999) from the same institution reported vital capacity at 3 weeks of 55±16% predicted with bilateral anterolateral thoracotomy versus 41±11% predicted with clamshell (p=0.043)[40].

Additional Benefits

Sternum-sparing approaches consistently demonstrate less blood loss, reduced transfusion requirements, shorter mechanical ventilation duration, and shorter ICU stays[1][2][5][9]. The mechanism appears related to preserved chest wall stability, enabling more effective breathing mechanics and earlier mobilization[2][6]. While operative and ischemic times may be slightly longer with bilateral anterolateral thoracotomy, survival outcomes are similar …

Verdict: 🟡 支持方向但精確數字不對 — 手冊 9.7% vs 22.8% 具體數字無法對應到現有研究；但多個世代研究（Venuta 2003、Langmuur 2025、Harefield 2016）一致顯示 anterolateral thoracotomy 傷口併發症少、3-6 月 FEV1 較佳

Article ID: 93ddbf1b-1f78-4ac5-be8d-8beea36506e6

Top citations: - Langmuur SJJ, Seghers L, Hoek RAS, et al.. 2025 Clin Transplantation. doi:10.1111/ctr.70406 [OE-Langmuur-2025-Anterolateral] - Venuta F, Rendina EA, De Giacomo T, et al.. 2003 Eur J Cardiothorac Surg. doi:10.1016/s1010-7940(03)00107-6 [OE-Venuta-2003-Bilateral] - Elde S, Huddleston S, Jackson S, et al.. 2017 Surgical Infections. doi:10.1089/sur.2017.144 [OE-Elde-2017-Incision] - Park JM, Son J, Kim DH, Son BS.. 2023 Yonsei Medical Journal. doi:10.3349/ymj.2023.0104 [OE-ParkJM-2023-SternumSparing] - Marczin N, Popov AF, Zych B, et al.. 2016 Interact Cardiovasc Thorac Surg. doi:10.1093/icvts/ivw004 [OE-Marczin-2016-MiniInvasive] - Park JH, Park S, Bae SY, et al.. 2026 Surgical Endoscopy. doi:10.1007/s00464-026-12689-6 [OE-ParkJH-2026-VATS] - Taghavi S, Bîrsan T, Seitelberger R, et al.. 1999 Ann Thorac Surg. doi:10.1016/s0003-4975(99)00228-3 [OE-Taghavi-1999-Anterolateral]

J.1.3 Q37 [Med] Ch05:144 PA 去鉗後 mPAP > 35

Q: In pulmonary arterial hypertension patients undergoing lung transplantation, does post-implant mPAP >35 mmHg or RV FAC <35% reliably predict need for planned VA-ECMO prolongation into the postoperative period?

A (OE 綜合): Specific numeric thresholds of post-implant mPAP >35 mmHg or RV FAC <35% have not been validated as reliable predictors for planned VA-ECMO prolongation after lung transplantation in PAH patients. The decision to prolong ECMO postoperatively is based on clinical judgment incorporating multiple factors rather than single hemodynamic or echocardiographic cutoffs.

Current evidence and practice patterns:

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus states that “there are clear situations with right ventricular dysfunction (for example, high pulmonary artery pressures) where patients should not be weaned off ECMO at the end of the transplantation,” but does not specify numeric thresholds[6][30]. The consensus recommends prophylactic post-transplantation ECMO maintenance in patients with pulmonary hypertension to reduce primary graft dysfunction and improve early outcomes[6][17][34].

Preoperative predictors studied (not post-implant):

Research has identified preoperative factors associated with need for extracorporeal support, including: - Severe RV dysfunction and moderate-to-severe tricuspid regurgitation[15] - Higher preoperative mPAP (OR 1.33 per 5 mmHg increase)[15] - RV dilation (OR 2.77)[15] - Preoperative echocardiographic parameters: RVSP 56.5 vs 37.8 mmHg, TAPSE 17.8 vs 19.9 mm in patients requiring vs not requiring mechanical support[12]

Clinical practice approach:

Many high-volume centers use a prophylactic strategy for PAH patients, maintaining VA-ECMO postoperatively based on the diagnosis itself and anticipated post-transplant heart failure, rather than specific post-implant measurements[5][8][18]. In one recent series, 17 of 20 PAH patients had VA-ECMO maintained postoperatively for a median of 4 days based on “anticipated post-LTx heart failure due to PAH and suboptimal cardiac function,” achieving 100% survival at 90 days and 1 year[5][18].

International consensus recommends that visual qualitative estimation of global RV function and dilation remains the expert’s choice to assess changes and decide if mechanical support is required, as quantitative methods may be technically challenging during rapid hemodynamic changes[16]. RV function and size should be assessed after pulmonary artery unclamping and reperfusion, with this information combined with concurrent hemodynamics to guide ECMO decisions[16].

Verdict: 🔴 推翻（閾值未驗證） — mPAP > 35 / RV FAC < 35% 具體閾值未經驗證；實務多採「預防性」策略 + 視覺質性評估 RV（Marczin 2021 共識；Kawashima 2025 實務）

Article ID: 37a6f694-8e84-46ea-9346-abbd32ef06ff

Top citations: - Hartwig M, van Berkel V, et al.. 2023 J Thorac Cardiovasc Surg. doi:10.1016/j.jtcvs.2022.06.024 [OE-AATS-2023-MCS-LTx] - Shah PR, Boisen ML, Winger DG, et al.. 2017 J Cardiothorac Vasc Anesth. doi:10.1053/j.jvca.2016.08.021 [OE-Shah-2017-ECMO-PAH] - Kubisa B, Kubisa A, Piotrowska M, et al.. 2022 Transplantation Proceedings. doi:10.1016/j.transproceed.2022.08.022 [OE-Kubisa-2022-RV] - Kawashima M, Ijiri N, Konoeda C, et al.. 2025 Eur J Cardiothorac Surg. doi:10.1093/ejcts/ezaf256 [OE-Kawashima-2025-Extended] - Moser B, Jaksch P, Taghavi S, et al.. 2018 Eur J Cardiothorac Surg. doi:10.1093/ejcts/ezx212 [OE-Moser-2018-Vienna] - Marczin N, de Waal EEC, Hopkins PMA, et al.. 2021 J Heart Lung Transplant. doi:10.1016/j.healun.2021.07.012

J.1.4 Q38 [Med] Ch05:148 Drain > 200 mL/h × 3h

Q: What evidence-based chest tube output threshold triggers re-exploration after lung transplantation — is >200 mL/hr for 3 hours validated, or are other thresholds (e.g., >400 mL/hr, >1500 mL/24hr) more commonly used?

A (OE 綜合): No specific chest tube output threshold for re-exploration after lung transplantation has been validated in the literature. The 2021 International Consensus Recommendations for lung transplantation provide only qualitative criteria: surgical re-exploration should be considered in patients with “ongoing blood loss despite correction of coagulopathy, hemodynamic instability, and profound hypoxia with associated mechanical compression of the lungs”[1][13]. No numeric thresholds (such as >200 mL/hr for 3 hours, >400 mL/hr, or >1500 mL/24hr) are specified in lung transplant-specific guidelines.

Clinical context from cardiac surgery literature

While lung transplant-specific thresholds are absent, cardiac surgery literature provides some reference points, though these cannot be directly extrapolated to lung transplantation:

  • >200 mL/hr threshold: One cardiac surgery study defined postoperative hemorrhage as ≥200 mL/hr in any 1 hour or ≥2 mL/kg/hr for 2 consecutive hours within the first 6 hours, which was associated with increased 30-day mortality and complications[11]. However, this was a retrospective definition, not a validated re-exploration trigger.

  • >1.5 mL/kg/hr for 6 hours: A multicenter cardiac surgery study defined active bleeding as >1.5 mL/kg/hr for 6 consecutive hours within 24 hours, which occurred in 2.6% of patients[7].

  • Higher thresholds: Pediatric cardiac surgery literature validated ≥7 mL/kg/hr for ≥2 consecutive hours in the first 12 hours or ≥84 mL/kg total for 24 hours as excessive bleeding[9].

Clinical decision-making considerations

The decision for re-exploration after lung transplantation appears to be based on clinical judgment rather than rigid numeric criteria. Key factors include[1][13]:

  • Hemodynamic stability: Unstable patients warrant earlier intervention
  • Coagulopathy correction: Ongoing bleeding despite normalized coagulation parameters suggests surgical source
  • Respiratory compromise: Profound hypoxia with mechanical lung compression from hemothorax
  • Timing: Cardiac surgery data suggest early re-exploration (within 4 hours) is associated with better outcomes compared to delayed intervention[12]

Lung transplant-specific bleeding considerations

Bleeding requiring reoperation occurs in approximately 4.5-7.2% of lung transplants[4][17]. Risk factors include low postoperative fibrinogen levels, use of extracorporeal membrane oxygenation, and severe adhesions from prior thoracic surgery[4][17]. Severe postoperative bleeding is associated with significantly decreased 60-day survival[17].

The absence of validated numeric thresholds likely reflects the complexity of lung transplant patients, where factors beyond chest tube output (graft function, hemodynamic status, coagulation parameters, and respiratory mechanics) must be integrated into the decision for re-exploration.

Verdict: 🔴 推翻（閾值未驗證） — 200 mL/hr × 3h 在 LTx 文獻中未驗證；ISHLT 2021 僅提供質性準則（持續出血 + 血流動力不穩 + 嚴重低氧）；應改為臨床判斷為主

Article ID: ceb13729-22d4-474e-9632-dfa17492e5b5

Top citations: - Marczin N, de Waal EEC, Hopkins PMA, et al.. 2021 J Heart Lung Transplant. doi:10.1016/j.healun.2021.07.012 - Christensen MC, Dziewior F, Kempel A, von Heymann C.. 2012 J Cardiothorac Vasc Anesth. doi:10.1053/j.jvca.2011.09.021 [OE-Christensen-2012-Hemorrhage] - Colson PH, Gaudard P, Fellahi JL, et al.. 2016 PloS One. doi:10.1371/journal.pone.0162396 [OE-Colson-2016-ActiveBleed] - Bercovitz RS, Shewmake AC, Newman DK, et al.. 2018 J Thorac Cardiovasc Surg. doi:10.1016/j.jtcvs.2017.12.038 [OE-Bercovitz-2018-PedsBleed] - Shou BL, Aravind P, Ong CS, et al.. 2023 Ann Thorac Surg. doi:10.1016/j.athoracsur.2022.07.037 [OE-Shou-2023-EarlyReop] - González D, Paradela M, Parente I, et al.. 2009 Transplantation Proceedings. doi:10.1016/j.transproceed.2009.06.014 [OE-Gonzalez-2009-Reop] - Adelmann D, Koch S, Menger J, et al.. 2019 Transplant International. doi:10.1111/tri.13491 [OE-Adelmann-2019-Bleed]

J.1.5 Q39 [High] Ch05:310-315 MP 500 mg (off-pump) vs 1 g (CPB)

Q: In lung transplantation at reperfusion, does methylprednisolone 500 mg vs 1 g IV reduce primary graft dysfunction grade 3 at 72 hours? Is the off-pump vs on-CPB dose distinction evidence-based? Any RCTs?

A (OE 綜合): No randomized controlled trials have directly compared methylprednisolone 500 mg versus 1 g at reperfusion for preventing PGD grade 3 at 72 hours in lung transplantation. The off-pump versus on-CPB dose distinction is not evidence-based and appears to be center-specific practice variation rather than supported by comparative trials.

Standard corticosteroid protocols at reperfusion

Published lung transplant protocols show variable methylprednisolone dosing at reperfusion:

  • 500 mg per allograft (total 1 g for bilateral): Used in the ScanCLAD trial (two 500 mg doses intraoperatively before reperfusion) and in a Johns Hopkins protocol (500 mg IV prior to reperfusion of each allograft)[15][20][35]

  • 1000 mg single dose: Used in an Austrian center protocol (1000 mg before revascularization)[34][49]

  • 125 mg every 8 hours: Used in older protocols starting at reperfusion[19]

These protocols were not stratified by use of cardiopulmonary bypass versus off-pump technique. The dose variation appears to reflect institutional practice rather than evidence-based adjustment for surgical approach.

Cardiopulmonary bypass and PGD risk

While CPB use is a strong independent risk factor for PGD grade 3 (OR 3.4 in the Lung Transplant Outcomes Group study; OR 4.24 versus off-pump in the ECLS Registry), there is no published evidence that higher methylprednisolone doses mitigate this risk[13][21][22]. Studies comparing CPB versus ECMO versus off-pump show:

  • PGD3 rates at 48-72 hours: off-pump 12.1%, ECMO 28.9%, CPB 42.7%[21]
  • CPB associated with greater cytokine release (IL-6, IL-8, TNF-alpha) compared to off-pump[24]
  • No trials testing whether dose escalation in CPB cases reduces PGD

Relevant evidence from cardiac surgery

The cardiac surgery literature (not lung transplant) shows that methylprednisolone dosing for CPB-related inflammation has been studied:

  • The SIRS trial used 500 mg total methylprednisolone in cardiac surgery with CPB and found no mortality benefit but possible reduction in atrial fibrillation[37][40]
  • Doses ranging from 5-30 mg/kg have been tested in cardiac surgery, with meta-analyses suggesting low-to-moderate doses may be as effective as high doses while avoiding adverse effects like hyperglycemia[39][40][44]

Current state of evidence

Treatment of PGD remains supportive with lung-protective ventilation and ECMO when needed. No targeted pharmacologic therapies, including specific corticosteroid dosing strategies, have been validated in RCTs for PGD prevention[4][27][28]. The 2003 review by de Perrot noted that “only three randomized, double-blinded, placebo-controlled trials on ischemia-reperfusion-induced lung injury have been reported in the literature”—and none compared different steroid doses[8].

The practice of using higher methylprednisolone doses (1 g vs 500 mg) in CPB cases lacks supporting evidence and likely represents extrapolation from the known higher inflammatory burden w…

Verdict: 🟡 修正（無 RCT） — 無 RCT 比較 500 mg vs 1 g at reperfusion；off/on-pump 劑量區分無證據；ScanCLAD 採 500 mg/allograft，Austrian 1000 mg 都有先例

Article ID: 869ee94e-f997-48ab-8b3d-95c90070c82a

Top citations: - Dellgren G, Lund TK, Raivio P, et al.. 2024 Lancet Respir Med. doi:10.1016/s2213-2600(23)00293-x [OE-Dellgren-2024-ScanCLAD] - Penninga L, Møller CH, Penninga EI, et al.. 2013 Cochrane Database Syst Rev. doi:10.1002/14651858.cd008927.pub2 [OE-Penninga-2013-Cochrane] - Aharinejad S, Taghavi S, Klepetko W, Abraham D.. 2004 Lancet. doi:10.1016/s0140-6736(04)16148-5 [OE-Aharinejad-2004-Prediction] - Diamond JM, Lee JC, Kawut SM, et al.. 2013 Am J Respir Crit Care Med. doi:10.1164/rccm.201210-1865oc [OE-Diamond-2013-LTOG] - Loor G, Huddleston S, Hartwig M, et al.. 2022 J Thorac Cardiovasc Surg. doi:10.1016/j.jtcvs.2021.10.076 [OE-Loor-2022-ECLS] - Chacon-Alberty L, Ye S, Elsenousi A, et al.. 2023 Artificial Organs. doi:10.1111/aor.14474 [OE-ChaconAlberty-2023-Albumin] - Whitlock RP, Devereaux PJ, Teoh KH, et al.. 2015 Lancet. doi:10.1016/s0140-6736(15)00273-1 [OE-Whitlock-2015-SIRS] - Pastores SM, Annane D, Rochwerg B.. 2018 Intensive Care Med. doi:10.1007/s00134-017-4951-5 [OE-Pastores-2018-Guidelines] - Bourbon A, Vionnet M, Leprince P, et al.. 2004 Eur J Cardiothorac Surg. doi:10.1016/j.ejcts.2004.07.044 [OE-Bourbon-2004-MPCPB] - Christie JD, Van Raemdonck D, Fisher AJ.. 2024 N Engl J Med. doi:10.1056/nejmra2401039

J.1.6 Q40 [Med] Ch05:316 PGE1 250 mg in NS 50cc, 4 cc/hr

Q: What is the evidence for intraoperative PGE1 (alprostadil) infusion dose (e.g., 250 mcg in NS 50cc at 4 cc/hr) reducing primary graft dysfunction after lung transplantation vs placebo or vs inhaled nitric oxide?

A (OE 綜合): No randomized controlled trials have evaluated intraoperative intravenous PGE1 (alprostadil) infusion versus placebo for preventing primary graft dysfunction (PGD) in human lung transplant recipients. The evidence base consists primarily of animal studies and observational human data, with PGE1 used predominantly in donor preservation solutions rather than as a continuous intraoperative infusion in recipients.

Animal Evidence

A canine lung transplant study demonstrated that continuous PGE1 infusion starting at implantation (mean dose 31.7 ± 6.9 ng/kg/min) significantly improved early graft function compared to controls receiving no PGE1. At 6 hours post-transplant, PGE1-treated animals had higher PaO2 (255.8 ± 37.6 vs 64.7 ± 7.9 mmHg, p<0.05) and better alveolar-arterial oxygen gradients[2]. Rat models showed that PGE1 administered during reperfusion reduced ischemia-reperfusion injury through anti-inflammatory mechanisms, with higher IL-10 levels and lower TNF-alpha, IFN-gamma, and IL-12 compared to saline controls[1][10].

Human Evidence - Inhaled PGE1

Human studies have focused on inhaled/aerosolized PGE1 rather than intravenous infusion. In 18 lung transplant patients, inhaled aerosolized PGE1 reduced mean pulmonary artery pressure, pulmonary vascular resistance, and shunt fraction while improving PaO2/FiO2 ratio without affecting systemic hemodynamics[26][40]. However, these effects were transient and reversed after discontinuation.

Current Clinical Practice

PGE1 is widely used in lung transplantation, but primarily as a bolus injection into the pulmonary artery (typically 500 mcg) and added to preservation solutions (500 mcg in flush solution) during donor procurement, not as a continuous intraoperative recipient infusion[4][7][8]. The mechanism involves pulmonary vasodilation, cAMP-mediated vascular protection, and anti-inflammatory effects rather than simple vasodilation alone[9][30].

Comparison to Inhaled Nitric Oxide

A 2022 randomized trial (n=201) compared inhaled epoprostenol (a prostacyclin analogue, not PGE1) to inhaled nitric oxide and found equivalent rates of grade 3 PGD (44.7% vs 39.8%, risk difference 4.9%, within equivalence margin)[13][14]. A smaller study (n=49) suggested inhaled nitric oxide reduced PGD incidence compared to controls (17.2% vs 45%, p<0.035)[18]. These studies evaluated inhaled pulmonary vasodilators, not intravenous PGE1.

Evidence Gaps

Despite widespread use in preservation solutions and theoretical benefits, no high-quality human trials have specifically tested the intraoperative intravenous PGE1 infusion protocol you describe (250 mcg in 50cc NS at 4 cc/hr) against placebo or inhaled nitric oxide for PGD prevention. Current international consensus guidelines emphasize reducing pulmonary vascular resistance and controlled reperfusion but do not specifically recommend routine intraoperative IV PGE1 infusion[24]. Recent reviews note that de…

Verdict: 🔴 推翻（無人體 RCT） — 250 mcg/50cc/4cc/hr 的連續 IV PGE1 infusion 無人體 RCT；PGE1 主要用於保存液或 PA bolus；吸入型（iNO、epoprostenol）Ghadimi 2022 等效；IV continuous 未驗證

Article ID: 4e9296fc-0846-4737-9d21-e64cf177dc25

Top citations: - Aoe M, Trachiotis GD, Okabayashi K, et al.. 1994 Ann Thorac Surg. doi:10.1016/0003-4975(94)90723-4 - de Perrot M, Fischer S, Liu M, et al.. 2001 Transplantation. doi:10.1097/00007890-200111150-00006 - Della Rocca G, Coccia C, Pompei L, et al.. 2008 Minerva Anestesiologica. pmid:18971891 - Yeung JC, Krueger T, Yasufuku K, et al.. 2017 Lancet Respir Med. doi:10.1016/s2213-2600(16)30323-x - Munshi L, Keshavjee S, Cypel M.. 2013 Lancet Respir Med. doi:10.1016/s2213-2600(12)70064-4 - Naka Y, Roy DK, Liao H, et al.. 1996 Circulation Research. doi:10.1161/01.res.79.4.773 - Ghadimi K, Cappiello J, Cooter-Wright M, et al.. 2022 JAMA Surgery. doi:10.1001/jamasurg.2021.5856 [OE-Ghadimi-2022-Epoprostenol] - Moreno I, Vicente R, Mir A, et al.. 2009 Transplantation Proceedings. doi:10.1016/j.transproceed.2009.05.019 [OE-Moreno-2009-iNO] - Marczin N, de Waal EEC, Hopkins PMA, et al.. 2021 J Heart Lung Transplant. doi:10.1016/j.healun.2021.07.012 - Chacon-Alberty L, Fernandez R, Jindra P, et al.. 2023 Transplantation. doi:10.1097/tp.0000000000004503

J.1.7 Q41 [High] Ch05:331-333 Reperfusion driving pressure < 15, FiO₂ < 30%

Q: In lung transplantation reperfusion and early postoperative ventilation, does driving pressure <15 cmH2O and FiO2 <30% reduce PGD3 at 72h compared to higher thresholds? Is there RCT or large cohort evidence supporting these specific cutoffs?

A (OE 綜合): Driving pressure ≤15 cmH2O is associated with reduced PGD3 and mortality after lung transplantation, but FiO2 <30% as a specific threshold lacks robust evidence. The available data come primarily from observational cohort studies rather than RCTs, and the FiO2 threshold is not well-defined in the literature.

Driving Pressure Evidence

A prospective observational study of 104 lung transplant recipients found that driving pressure ≤15 cmH2O at ICU admission was associated with significantly better 90-day survival compared to >15 cmH2O[2]. The low driving pressure group had significantly fewer patients with PGD3 (specific percentages not provided in abstract), less pneumonia, shorter ventilator time, and shorter ICU stays. In multivariable analysis, driving pressure and pneumonia were the only variables independently associated with 90-day mortality[2].

This 15 cmH2O threshold aligns with ARDS literature, where driving pressure >15 cmH2O is associated with increased lung stress and mortality[6][22]. However, the lung transplant-specific evidence for this cutoff comes from a single prospective observational study rather than an RCT[2].

FiO2 Evidence

For FiO2, the evidence is less specific to a 30% threshold. A large multicenter prospective cohort study (Lung Transplant Outcomes Group, n=1,255) found that higher FiO2 during allograft reperfusion was independently associated with PGD3 (OR 1.1 per 10% increase in FiO2; 95% CI 1.0-1.2; P=0.01)[7]. This suggests a continuous relationship rather than a specific threshold. A 2025 meta-analysis confirmed higher reperfusion FiO2 as a risk factor for PGD (OR 1.13; 95% CI 1.01-1.23)[9].

An international survey of lung transplant programs found that most clinicians (69%) preferred limiting FiO2 rather than increasing PEEP when managing oxygenation[5][16]. However, no specific FiO2 threshold of 30% was identified in the literature.

Lung Protective Ventilation Strategies

International consensus guidelines recommend lung protective ventilation including low tidal volumes (<6 mL/kg predicted body weight), appropriate PEEP, consideration of driving pressures, and avoidance of high inspiratory pressures[28]. A retrospective cohort study (n=373) found that donor-based lung protective ventilation (6-8 mL/kg donor ideal body weight and plateau pressure <30 cmH2O) was associated with significantly lower PGD3 risk (OR 0.44; 95% CI 0.29-0.68; p<0.001) and 1-year mortality[1][13].

RCT Evidence

The only identified RCT of intraoperative protective ventilation in lung transplantation (n=30) compared an open-lung strategy (recruitment maneuvers, pressure-controlled ventilation) to conventional low tidal volume ventilation[17][21]. While the primary outcome (PaO2/FiO2 at 24 hours) showed no significant difference, the intervention group had better oxygenation at surgery end and shorter time to extubation. This small trial did not specifically evaluate the driving pressure or FiO2 threshold…

Verdict: 🟡 修正（部分支持） — Driving pressure ≤15 有 Xuan 2024 前瞻觀察支持；FiO₂ < 30% 無特定閾值；FiO₂ 應持續越低越好（Diamond 2013 LTOG: OR 1.1/10%）

Article ID: aeaa6e11-635b-4de3-81a5-f016c5d56641

Top citations: - Xuan C, Gu J, Chen J, Xu H.. 2024 J Int Med Res. doi:10.1177/03000605241259442 - Gorman EA, O’Kane CM, McAuley DF.. 2022 Lancet. doi:10.1016/s0140-6736(22)01439-8 [OE-Gorman-2022-ARDS] - Diamond JM, Lee JC, Kawut SM, et al.. 2013 Am J Respir Crit Care Med. doi:10.1164/rccm.201210-1865oc [OE-Diamond-2013-LTOG] - Pan J, Zhang J, Lu X.. 2025 Surgery Today. doi:10.1007/s00595-025-03129-4 - Beer A, Reed RM, Bölükbas S, et al.. 2014 Ann Am Thorac Soc. doi:10.1513/annalsats.201312-419oc [OE-Beer-2014-MechVent] - Marczin N, de Waal EEC, Hopkins PMA, et al.. 2021 J Heart Lung Transplant. doi:10.1016/j.healun.2021.07.012 - Tague LK, Bedair B, Witt C, et al.. 2021 J Heart Lung Transplant. doi:10.1016/j.healun.2021.06.016 - Verbeek GL, Myles PS, Westall GP, et al.. 2017 Anaesthesia. doi:10.1111/anae.13964 [OE-Verbeek-2017-OpenLung]

J.1.8 Q42 [High] Ch05:544-547 MTP trigger + 1:1:1 ratio

Q: In lung transplantation with massive hemorrhage, does 1:1:1 PRBC:FFP:platelets transfusion ratio vs goal-directed ROTEM/TEG-guided hemostatic management reduce mortality and total transfusion volume? MTP trigger at >150 mL/min blood loss or >4 units PRBC/hr supported?

A (OE 綜合): Based on the available evidence, goal-directed ROTEM/TEG-guided hemostatic management appears superior to fixed 1:1:1 ratio transfusion in lung transplantation, reducing total transfusion volume without increasing mortality. However, no direct head-to-head comparison exists specifically in lung transplantation with massive hemorrhage, and the evidence comes primarily from trauma and cardiac surgery populations.

Comparative Evidence in Lung Transplantation

In lung transplantation specifically, ROTEM-guided management demonstrates clear benefits over empiric transfusion:

  • A randomized trial of 67 bilateral lung transplant patients found ROTEM-guided management significantly reduced perioperative blood loss (p=0.013), RBC consumption (p=0.009), and FFP use (p<0.0001, with practically no FFP used in the ROTEM group) compared to clinical judgment-based management[7]

  • A before-after study of 93 lung transplant patients showed ROTEM/multiplate point-of-care testing reduced the proportion receiving PRBCs (87% vs 65%, p=0.015), FFP (72% vs 30%, p<0.0001), and platelets (70% vs 37%, p=0.002), with blood product costs decreasing from $3,935 to $991 (p<0.001). No mortality difference was detected (6% vs 2%, p=0.617)[4][30]

  • ROTEM-guided management combined with albumin resuscitation improved early allograft function (Horowitz index 403 vs 308, p<0.001) and reduced severe PGD at 72 hours (3.2% vs 25%, p=0.003)[29]

Important Caveat for Lung Transplantation: High FFP:RBC ratios may be detrimental in lung transplant recipients. A retrospective study of 89 patients receiving >4 units PRBCs found that high FFP:RBC ratios (>1:2) were associated with higher rates of severe PGD at 72 hours (60.5% vs 23.5%, p=0.0013) and longer hospital stays (40 vs 32 days, p=0.0273)[27]. This suggests the 1:1:1 ratio approach from trauma may not be appropriate for lung transplantation.

Evidence from Trauma and Cardiac Surgery

The 1:1:1 vs goal-directed comparison has been studied more extensively in trauma:

  • A 2025 Cochrane review found no mortality difference between VHA-guided and conventional coagulation test-guided management at 24 hours (RR 0.85, 95% CI 0.54-1.35) or 30 days (RR 0.75, 95% CI 0.48-1.17, very low certainty)[1]

  • The landmark PROPPR trial in trauma found no mortality difference between 1:1:1 and 1:1:2 ratios at 24 hours (12.7% vs 17.0%, p=0.12) or 30 days (22.4% vs 26.1%, p=0.26), though 1:1:1 achieved hemostasis faster with fewer exsanguination deaths[20][24]

  • In cardiac surgery, TEG/ROTEM-guided algorithms reduced blood loss by 103 mL (95% CI 50-157 mL) and transfusion rates for RBCs (RR 0.89), FFP (RR 0.59), and platelets (RR 0.81) in randomized trials[9]. A 2025 meta-analysis suggested possible mortality reduction (RR 0.76, 95% CI 0.63-0.92), though evidence certainty was very low[11][12]

MTP Activation Triggers

Regarding specific triggers of >150 mL/min blood loss or >4 units PRBC/hr:

  • The ASA guidelines…

Verdict: 🟢 修正（1:1:1 有害） — ROTEM/TEG-guided 優於 fixed ratio；Seay 2020 顯示 LTx 中高 FFP:RBC 比增加 PGD3 (60.5% vs 23.5%)；手冊應改 ROTEM-guided + 警告避免 1:1:1

Article ID: d25bde3c-7db1-40cf-9c9f-23ef3eec7015

Top citations: - Durila M, Vajter J, Garaj M, et al.. 2021 J Heart Lung Transplant. doi:10.1016/j.healun.2021.03.020 [OE-Durila-2021-ROTEM-RCT] - Smith I, Pearse BL, Faulke DJ, et al.. 2017 J Cardiothorac Vasc Anesth. doi:10.1053/j.jvca.2016.06.027 [OE-Smith-2017-ROTEM-LTx] - Vajter J, Vachtenheim J, Prikrylova Z, et al.. 2023 BMC Pulmonary Medicine. doi:10.1186/s12890-023-02372-0 [OE-Vajter-2023-Albumin] - Seay T, Guinn N, Maisonave Y, et al.. 2020 J Cardiothorac Vasc Anesth. doi:10.1053/j.jvca.2020.05.043 [OE-Seay-2020-HighFFP] - Brunskill SJ, Disegna A, Wong H, et al.. 2025 Cochrane Database Syst Rev. doi:10.1002/14651858.cd012635.pub2 [OE-Brunskill-2025-Cochrane] - Holcomb JB, Tilley BC, Baraniuk S, et al.. 2015 JAMA. doi:10.1001/jama.2015.12 [OE-Holcomb-2015-PROPPR] - Li C, Zhao Q, Yang K, Jiang L, Yu J.. 2019 J Thoracic Disease. doi:10.21037/jtd.2019.04.39 [OE-Li-2019-TEGmeta] - Kvisselgaard AD, Wolthers SA, Wikkelsø A, et al.. 2025 Acta Anaesthesiol Scand. doi:10.1111/aas.70127 [OE-Kvisselgaard-2025-Rapid] - Kvisselgaard AD, Wolthers SA, Wikkelsø A, et al.. 2025 Acta Anaesthesiol Scand. doi:10.1111/aas.14558 [OE-Kvisselgaard-2025-TEGsurg] - -. 2015 Anesthesiology. doi:10.1097/aln.0000000000000463 [OE-ASA-2015-Perioperative]

J.1.9 Q43 [High] Ch05:551 TXA 1 g + 1 g/8h

Q: In lung transplantation, does tranexamic acid (TXA) 1g bolus + 1g over 8 hours reduce blood loss without increasing thrombosis compared to placebo or no-TXA? Cite evidence from cardiac surgery extrapolated or lung-transplant-specific studies.

A (OE 綜合): No lung transplant-specific randomized controlled trials of tranexamic acid (TXA) have been published. However, extrapolation from cardiac surgery and general thoracic surgery provides relevant evidence for the dosing regimen in question (1g bolus + 1g over 8 hours).

Evidence from Cardiac Surgery

In cardiac surgery with cardiopulmonary bypass—a setting with similar coagulopathy, fibrinolysis, and bleeding risk to lung transplantation—TXA consistently reduces blood loss and transfusion requirements without increasing thrombotic complications[1][4][12][29].

The OPTIMAL trial (2022) compared high-dose (30 mg/kg bolus + 16 mg/kg/h infusion) versus low-dose (10 mg/kg bolus + 2 mg/kg/h infusion) TXA in 3,079 cardiac surgery patients[17]. High-dose TXA reduced red blood cell transfusion by 4.1% (21.8% vs 26.0%, P=0.004) and met noninferiority criteria for the composite safety endpoint of death, seizure, kidney dysfunction, and thrombotic events (17.6% vs 16.8%)[17]. The proposed regimen (1g bolus + 1g over 8 hours, approximately 14 mg/kg bolus + 1.8 mg/kg/h for a 70kg patient) falls between these doses.

The ATACAS trial (2017) in 4,631 coronary artery surgery patients found TXA reduced major hemorrhage requiring reoperation (1.4% vs 2.8%, P=0.001) without increasing the composite of death or thrombotic complications (16.7% vs 18.1%, P=0.22)[29][30]. However, seizures occurred more frequently with TXA (0.7% vs 0.1%, P=0.002), particularly in open-chamber procedures[29].

Exposure-response analysis suggests low-dose regimens (total dose ~20 mg/kg) approach 80% of maximal hemostatic effect, while high-dose regimens (80-100 mg/kg) exceed 90% effectiveness but with only modest additional benefit and higher seizure risk[18]. A 1g bolus + 1g infusion (total ~28 mg/kg for 70kg patient) represents a moderate dose likely to provide substantial hemostatic benefit.

Evidence from Thoracic Surgery

A 2025 matched-pair analysis from the German Thorax Registry (1,034 thoracic surgery patients) found prophylactic TXA did not significantly reduce bleeding complications or transfusion requirements, but thromboembolic complications were significantly less frequent in the TXA group (1.0% vs 5.1%)[2][15]. This paradoxical finding contrasts with theoretical thrombotic concerns and suggests TXA may not increase—and may even reduce—thrombotic risk in thoracic surgery[2].

Safety Profile

Multiple meta-analyses confirm TXA does not increase myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism in surgical patients[1][4][12]. The 2021 JAMA Surgery meta-analysis found no association between TXA and thromboembolic events across diverse surgical settings[3]. A 2022 umbrella review of 47 meta-analyses concluded TXA demonstrates hemostatic effects without increasing vascular adverse events, though seizure risk exists in cardiac surgery (dose-dependent)[5].

Dosing Considerations

The 1g bolus + 1g over 8 hours r…

Verdict: 🟢 支持（cardiac 外推） — 無 LTx 專屬 RCT；但 OPTIMAL 2022、ATACAS 2017、German Thorax Registry 2025 支持；1g bolus + 1g/8h 介於 low/high dose 範圍內，合理

Article ID: 05a1e2de-7208-4d73-bc2f-3105c8a32247

Top citations: - -. 2015 Anesthesiology. doi:10.1097/aln.0000000000000463 [OE-ASA-2015-Perioperative] - Ker K, Edwards P, Perel P, Shakur H, Roberts I.. 2012 BMJ. doi:10.1136/bmj.e3054 [OE-Ker-2012-TXAmeta] - Myles PS, Smith JA, Forbes A, et al.. 2017 N Engl J Med. doi:10.1056/nejmoa1606424 [OE-Myles-2017-ATACAS] - Shi J, Zhou C, Pan W, et al.. 2022 JAMA. doi:10.1001/jama.2022.10725 [OE-Shi-2022-OPTIMAL] - Zufferey PJ, Lanoiselée J, Graouch B, et al.. 2021 Anesthesiology. doi:10.1097/aln.0000000000003633 [OE-Zufferey-2021-TXAExposure] - Schieren M, Collaud S, Bonberg L, et al.. 2025 J Cardiothorac Vasc Anesth. doi:10.1053/j.jvca.2025.06.005 [OE-Schieren-2025-ThoraxTXA] - Taeuber I, Weibel S, Herrmann E, et al.. 2021 JAMA Surgery. doi:10.1001/jamasurg.2021.0884 [OE-Taeuber-2021-TXAmeta] - Hong P, Liu R, Rai S, et al.. 2022 Front Pharmacol. doi:10.3389/fphar.2022.887386 [OE-Hong-2022-TXAumbrella] - Hunt BJ.. 2015 Anaesthesia. doi:10.1111/anae.12910 [OE-Hunt-2015-TXAreview] - Karanicolas PJ, Lin Y, McCluskey SA, et al.. 2024 JAMA. doi:10.1001/jama.2024.11783 [OE-Karanicolas-2024-TXA-CABG]

J.1.10 Q44 [Low] Ch05:562 血糖 < 180 mg/dL

Q: In thoracic organ transplantation (lung or heart) intraoperative and early postoperative care, does glucose <180 mg/dL target vs <140 vs <200 reduce wound infection, mortality, or graft dysfunction? Any RCT evidence specific to transplantation?

A (OE 綜合): No RCT evidence exists specifically comparing glucose targets (<140 vs <180 vs <200 mg/dL) in thoracic organ transplantation (heart or lung). However, one RCT in liver transplantation and observational data in heart and lung transplantation provide relevant insights.

Evidence from Solid Organ Transplantation

The only transplant-specific RCT comparing glucose targets was conducted in liver transplant recipients[4]. This study randomized 164 patients to targets of 140 mg/dL versus 180 mg/dL and found: - Infection reduction: The 140 mg/dL group had significantly fewer infections within 1 year (42.7% vs 65.9%, P=0.0046), with a hazard ratio of 0.54 (95% CI 0.35-0.83)[4] - No difference in graft rejection: Rejection rates were similar between groups (20.7% vs 24.3%)[4] - Increased moderate hypoglycemia: More patients in the 140 mg/dL group experienced moderate hypoglycemia (glucose 41-70 mg/dL): 32.9% vs 12.2% (P=0.003)[4] - No mortality difference: The study did not show mortality differences, though it may have been underpowered for this outcome[4]

Observational Data in Thoracic Transplantation

In heart transplantation, one retrospective study of 92 patients using intensive glycemic control (target 80-110 mg/dL) showed no differences in mortality, rejection, infections, or other surgical outcomes between diabetic and non-diabetic patients, with low hypoglycemia rates[13]. However, this was not a comparative trial.

In lung transplantation, observational data demonstrate that poor glycemic control correlates with mortality. Each 18 mg/dL increase in mean random blood glucose was associated with a 38% increase in mortality (95% CI 15-65%, P<0.001)[11][29]. However, no RCTs have tested specific glucose targets.

General Transplant Recommendations

Current expert consensus for solid organ transplantation recommends a target of <180 mg/dL with minimal hypoglycemia (<70 mg/dL) during the early post-transplant period[6][24][27]. The American Diabetes Association guidelines recommend perioperative glucose targets of 100-180 mg/dL for most surgical patients, with more stringent targets (110-140 mg/dL) potentially appropriate for cardiac surgery if achievable without significant hypoglycemia[2][3][15].

Cardiac Surgery Evidence (Not Transplant-Specific)

In general cardiac surgery populations, perioperative tight glucose control (<150 mg/dL) may reduce surgical site infections compared to conventional control, but increases hypoglycemia risk[18][19]. The ACC/AHA guidelines recommend maintaining glucose <180 mg/dL during CABG to reduce sternal wound infections[14][16]. However, the optimal target remains controversial, with one study showing no benefit of 100-140 mg/dL versus 141-180 mg/dL targets[16].

Clinical Implications

For thoracic organ transplantation specifically, no RCT evidence exists to guide choice between <140, <180, or <200 mg/dL targets. The single liver transplant RCT suggest…

Verdict: 🟡 修正（無 LTx RCT） — 無 thoracic Tx 專屬 RCT；liver Tx RCT 顯示 140 vs 180 感染減少（HR 0.54）但低血糖增加；建議 140-180 為可行目標；Hackman 2017 顯示高血糖與 LTx 死亡率相關

Article ID: 15ed1016-24ac-4dc6-95a9-2ed14861a1b2

Top citations: - Wallia A, Schmidt K, Oakes DJ, et al.. 2017 J Clin Endocrinol Metab. doi:10.1210/jc.2016-3279 [OE-Wallia-2017-LTxGlycemic] - Garcia C, Wallia A, Gupta S, et al.. 2013 Clinical Transplantation. doi:10.1111/ctr.12118 [OE-Garcia-2013-Heart] - Hackman KL, Snell GI, Bach LA.. 2017 Transplantation. doi:10.1097/tp.0000000000001555 [OE-Hackman-2017-LTxGlucose] - Galindo RJ, Wallia A.. 2016 Current Diabetes Reports. doi:10.1007/s11892-015-0707-1 [OE-Galindo-2016-Hyperglycemia] - ADA Professional Practice Committee. 2026 Diabetes Care. doi:10.2337/dc26-s016 [OE-ADA-2026-S16] - Sun Y, Wen Z, Ren Y, Hua Z.. 2025 J Clin Anesth. doi:10.1016/j.jclinane.2025.112051 [OE-Sun-2025-Perioperative] - Rogers LJ, Vaja R, et al.. 2024 Cochrane Database Syst Rev. doi:10.1002/14651858.cd013332.pub2 [OE-Rogers-2024-Cochrane] - Lawton JS, Tamis-Holland JE, Bangalore S, et al.. 2022 JACC. doi:10.1016/j.jacc.2021.09.006 [OE-Lawton-2022-ACC-CABG]

J.2 批次總結

Verdict 數量 題號
🟢 修正（證據方向反 / 外推支持） 3 Q35, Q42, Q43
🟡 修正（無 RCT / 部分支持） 4 Q36, Q39, Q41, Q44
🔴 推翻（閾值未驗證 / 無證據） 3 Q37, Q38, Q40

手冊 Ch05 必要修訂： - Q35 Heparin 100 IU/kg ACT~300 → 40-75 IU/kg ± 免 ACT（coated circuit + TXA；Vajter 2024、Chan 2025） - Q37 移除 mPAP>35 / RV FAC<35% 具體閾值；改為「質性評估 + 預防性策略」（Marczin 2021 / Kawashima 2025） - Q38 移除 200 mL/hr × 3h 閾值；改為臨床判斷（持續出血 + 血流動力不穩 + 低氧；ISHLT 2021） - Q40 移除 IV PGE1 continuous infusion routine；保留 PA bolus / preservation only；iNO 或 iEpoprostenol 為 PGD 輔助 - Q42 反轉 1:1:1 建議 → ROTEM/TEG-guided（Seay 2020 警示：LTx 高 FFP:RBC 比增加 PGD3） - Q39 註明 MP 500 mg vs 1 g 無 RCT；on/off-pump 劑量區分無證據 - Q41 保留 driving pressure ≤15；刪除 FiO₂ 30% 門檻，改為「盡量降低」 - Q44 改為 140-180 mg/dL 目標（liver Tx RCT 外推）