非外傷性心停止に対する大動脈の蘇生血管内バルーン閉塞（REBOA）の使用：レビュー
概要
非外傷性心停止（ＮＴＣＡ）を管理するための新しいアプローチとして、蘇生による大動脈の血管内バルーン閉塞（ＲＥＢＯＡ）が提案されている。心停止中、心拍出量は停止し、重要臓器の灌流が損なわれます。従来の高度な心臓生命維持（ACLS）対策と心肺蘇生法は、しばしば自然循環（ROSC）の回復を達成できません。REBOAの挿入中、バルーン先端のカテーテルが大腿動脈に挿入され、患者が心肺蘇生法（CPR）を受けている間、逆行性の方法で大動脈内に進められます。次に、バルーンを膨らませて大動脈を完全に閉塞します。非外傷性心停止における大動脈閉塞の使用に関する文献は、動物実験、症例報告、および最近の1件の非管理型実現可能性試験に限定されています。人間と動物の両方の研究で、予備データはREBOAが心停止蘇生中の冠状動脈および脳の灌流圧と主要な生理学的パラメーターを改善する可能性があることを示し、動物データはROSCの改善率を示しています。REBOAがACLSの付属物と見なされる前に、複数の質問が残っています。REBOAは、臨床的に有効であることが示されている場合、非外傷性心停止患者の生活の質を改善する可能性のある、費用対効果が高く、一般化可能な介入の可能性があります。
1はじめに
心停止は米国で毎年500,000人以上の成人に影響を及ぼし、退院まで生存するのは10％未満です。1過去数十年にわたる技術と心停止の管理の進歩にもかかわらず、患者中心の結果はいらいらするほどに低いままでした。1非外傷性心停止（NTCA）中、従来の高度な心臓生命維持（ACLS）介入では、自然循環の回復（ROSC）を達成できないことがよくあります。2胸骨圧迫は、適切な技術と理想的な条件にもかかわらず、ベースライン心拍出量の20％〜30％しか提供しません。３心肺蘇生法（CPR）中に生成される限られた血流は、大動脈を適切に拡張できず、冠動脈灌流圧（CPP）と心筋血流の主要な決定要因である大動脈拡張期圧を十分に上げることができません。
大動脈の蘇生血管内バルーン閉塞（REBOA）は、もともと非圧縮性体幹出血を管理するための出血制御技術として開発されました。腹腔内出血を伴う外傷患者のショック状態を一時的に緩和するために最も頻繁に使用されます。4バルーン先端のカテーテルを大腿動脈に挿入し、逆行して大動脈に挿入します。次に、バルーンを膨張させて大動脈を閉塞し、バルーンの近位の臓器への灌流を最大化し、遠位の流れを最小化して失血を遅らせます。5 REBOAは、外傷で負傷した患者に使用した場合、蘇生的開胸術と大動脈交差クランプ術に代わる低侵襲の代替手段ですが、外傷におけるその有効性を取り巻くエビデンスはまちまちで、無作為化試験データはありません。
REBOAによる大動脈閉塞は、心拍出量を胸部大動脈血管系に制限することにより、心筋および脳の血流を改善する可能性があります。これらの有利な生理学的変化を考えると、REBOAはNTCAの治療のための新しい介入として提案されています。図1に示すように、REBOAを胸部閉鎖型CPRと組み合わせて使用すると 、大動脈圧、CPP、および脳血流が改善される可能性があります。これは効果的にCPRの効率を高め、救急医にROSCと神経学的に無傷の生存のための条件を最適化するユニークなメカニズムを提供します
この記事では、NTCA中のREBOAの使用とREBOAに関連する動物および人間のデータをレビューし、NTCAに対するREBOAの将来について説明します。EMBASEおよびSCOPUSデータベースは、1946年から2020年5月に公開された関連記事を検索しました。検索に使用されたキーワードは、「大動脈バルーン閉塞」、「REBOA」、および「心停止」の組み合わせで構成されていました。アブストラクトは最後の著者によって評価され、すべての関連論文がこのレビューに含まれていました。特定された各論文の参照は、最初の検索で特定されなかったNTCAでのREBOAの使用に関連する記事について精査されました。トラウマで使用するためのREBOAの成長する経験を考えると、それはNTCAの議論に関連する類似物を提供し、参照されます。しかし、トラウマとNTCAの病態生理学の疫学における明確な違いに照らして、
2心臓アレスト生理学
通常、冠血流は主に拡張期に発生し、大動脈圧の生理的範囲にわたる局所組織の酸素需要と微小血管の自己調節メカニズムによって主に調節されます。7心停止状態では、深部組織低酸素症により微小血管が完全に拡張し、冠血流の主な原因は冠血管系全体の圧力勾配です。8このCPPは、大動脈圧から右心房圧を差し引いたものとして定義されます。9心筋収縮がないと冠状動脈の血流が持続しますが、CPPは胸骨圧迫の弛緩期に最も大きいことが研究で示されています。9 - 11
NTCAの間、CPPがゼロに向かって低下すると、心拍出量が停止し、静脈系内の血液プールと末梢動脈が徐々に拡張します。従来のACLS介入の目標は、ROSCを促進するためにCPPを増やすことです。NTCA中に15 mmHgを超える持続CPPは、ROSCと生存率の増加を非常に予測できることが研究によって示されています。9、12、13伝統的な介入は、しばしばも最適条件下CPP> 15 mmHgのを生成することができません。14 CPR血流はわずかです。正のCPPを生成するには最大60秒のCPR、15 mmHgを超えるCPPを得るには90秒かかります。9、15さらに、CPPの増加が推奨されている静脈内アドレナリンは、神経学的転帰の改善をもたらしていません。16、17は、これらの欠点を考えると、NTCAの死亡率は何十年もほぼ横ばいとなっています。18効果的な標準治療の不足と血管内デバイス技術の改善により、研究者はREBOAなどの新しい治療法を従来のACLSの補助として検討するようになりました。
3 CPR中のREBOAデプロイメント
REBOAカテーテル留置は、胸部、頭、および上肢がCPRおよびACLSの介入を実行するために他の人がアクセス可能な状態のまま実行できます。19総大腿動脈は、ポイントオブケア超音波検査とセルディンガー法を使用してアクセスされます。5経験豊富な開業医の手で、REBOAは1人の医師が約5〜10分で配備できます。
REBOAカテーテルは、大動脈の3つのゾーンのうちの1つに逆行して進められます。ゾーン1、左鎖骨下動脈と腹腔軸の間の下降する胸部大動脈。ゾーン2、腹腔軸から腎動脈までの傍内臓大動脈。ゾーン3、腎臓下大動脈。21図1に示すように、現在、NTCAにはゾーン1の配置が推奨されています 。ER-REBOAカテーテル（Prytime Medical、Boerne、TX）は、現在最も一般的に使用されている装置であり、カテーテルシャフトに組み込まれたマーカーを使用して、推定距離に基づいて透視なしで配置できます。22 対照的に、Coda Balloon Catheter（Cook Medical、Bloomington、IN）やREBOA Balloon Kit（Reboa Medical、Norway）などのオーバーザワイヤーカテーテルは、ガイドワイヤーの先端の深さがX線で確認された後に挿入されます。23、24ブラインド配置解剖学的ランドマークを用いた手法と推定距離は、外傷患者におけるREBOAの使用のために開発されました。25、26、このブラインド技術はNTCA中に使用する可能性が十分であるとエール大学での第1相臨床試験で現在使用中です。
REBOAカテーテルの先端にあるバルーンを目的の位置にすると、放射線不透過性の溶液で膨らみ、大動脈を完全に閉塞します。放射線不透過性のソリューションにより、医師は透視またはプレーンフィルムイメージングでREBOAの配置を確認できますが、超音波を使用して確認することもできます。28、29の場合ROSCは、バルーンがREBOAカテーテルが適所に残って収縮させることができるが得られます。カテーテルが除去された後、動脈導入シースは、動脈圧モニタリングおよび心臓カテーテル法に使用されるか、体外膜酸素化（ECMO）用に大型化されます。大きなREBOAカテーテル（> 8 Fr）の場合、いったん除去すると血管の修復が必要になる場合がありますが、これは小さなカテーテルの場合はそれほど起こりません。
4動物の非外傷性心臓病巣におけるリボア
ブタの心臓および大動脈の解剖学的構造は人間と類似しているため、REBOA研究の大部分は、心室細動のブタモデルで行われます。31 CPRにおけるREBOAの血行力学的利点は、20年以上前に最初に概説されました。32, 33 Multiple studies have shown thoracic aortic occlusion improves cerebral and coronary perfusion pressures, coronary blood flow, end‐tidal carbon dioxide, and overall mortality.32, 34-39 In one notable study of adult swine, during alternating periods of intra‐aortic balloon inflation and deflation, balloon inflation increased CPP by an average of 13.7 mmHg (60%) and coronary blood flow increased by 15.5 mL/min (8.5%).35 Of note, there is substantial variance in response to REBOA during cardiac arrest despite laboratory models attempting to control for factors that influence hemodynamics during CPR.
Traditionally animal studies have utilized Zone 1 placement of REBOA, as a more proximal level of occlusion would theoretically result in maximal hemodynamic benefit. Recent animal studies have further divided Zone 1 into 3 subzones (a‐c). Occlusion in Zone 1c (at the level of the diaphragm) augmented proximal arterial pressures and reduced arterial lactate concentrations better than occlusion in Zone 1b (at the level of the heart).40 This may be because of impaired ventricular expansion due to the location of the balloon directly deep to the heart, although it is unclear if this finding will translate to human physiology.
Two recent studies published in 2020 have demonstrated improved proximal physiology with Zone 1 placement when compared to Zone 3 placement.41, 42 Although Zone 3 occlusion would benefit visceral perfusion and possibly prevent ischemic injury, any hemodynamic benefit was transient or did not translate to improved outcomes.41, 42
5 REBOA IN HUMAN NON‐TRAUMATIC CARDIAC ARREST
The literature surrounding the use of aortic occlusion in human patients is limited to case reports and one recent non‐controlled feasibility trial.19 The first description of aortic occlusion, from Deakin et al in 1996, describes 2 patients who suffered cardiac arrests with an intra‐aortic balloon pump in place. Both patients underwent aortic occlusion through the continuous inflation of the intra‐aortic balloon pump and had immediate increases in systolic, diastolic, and coronary perfusion pressure. Neither patient survived.43 The generalizability of this report is limited as one patient had infective endocarditis and the other was immediately post coronary artery bypass graft.
Thirteen years later in 2009, Aslanger et al described a case that may be more representative of the majority of NTCA patients. A 74‐year‐old female was taken to the cardiac catheterization laboratory for an acute myocardial infarction and suffered from a cardiac arrest during the procedure.44 After 25 minutes of traditional ACLS, she underwent aortic occlusion with an intra‐aortic balloon pump while in asystole, followed by sustained ROSC 1 minute later. She was discharged from the hospital eventually and made a “good recovery.”44
In June 2019, Coniglio et al reported on the first case where a REBOA catheter was used in the emergency department for NTCA as a bridge therapy to an intra‐aortic balloon pump.45 Following aortic balloon inflation in the ED, the patient's ETCO2 increased from 8–20 mmHg, hemodynamics stabilized, and sustained ROSC was achieved. The REBOA catheter was replaced with an intra‐aortic balloon pump. Unfortunately, the patient developed a post‐cardiac arrest coagulopathy and ultimately died. However, this report demonstrates the potential effectiveness of REBOA in NTCA to increase coronary perfusion and act as a bridge to a more definitive intra‐vascular therapy. In November 2019, a Norwegian group reported out‐of‐hospital deployment of REBOA in 10 NTCA subjects treated by helicopter emergency medical services.19 Femoral artery cannulation for REBOA was successful on first attempt in 8 of 10 patients and on second attempt in the 2 remaining patients. The cohort consisted of 7 men and 3 women aged 50–74 years old. Mean time from dispatch to balloon occlusion was 45.6 minutes, procedural time ranged from 8–16 minutes, and ETCO2 increased a mean of 13 mmHg after 60 seconds of occlusion (P < 0.001). Similar to laboratory studies, the graph of ETCO2 measurements for individual patients showed substantial variability with some patients having large increases in ETCO2 whereas others showed little effect. This is the first report to demonstrate that REBOA is temporally associated with improvements in CPR quality as measured by ETCO2. Six of the 10 enrolled patients achieved ROSC (60%), 3 patients (30%) were admitted to the hospital, and 1 survived to hospital discharge with good neurologic outcome. In the patient who survived with a favorable neurologic outcome, investigators did not achieve aortic occlusion until 60 minutes into his asystolic NTCA. REBOA was again used as a rapidly deployable bridge therapy to a more definitive intervention and was converted to ECMO later in the patient's course.
Emergency medicine investigators at Yale University are currently enrolling subjects in the first United States Phase I clinical trial of REBOA in ou‐of‐hospital NTCA patients presenting to the ED.27 Investigators will measure real‐time diastolic blood pressure and patients will have no‐flow times that are more typical of those seen in urban populations. Two of 5 initial subjects have been enrolled at the time of this writing, each with immediate and sustained improvements in ETCO2 and mean arterial blood pressure and transient ROSC in one. Despite this, both patients were in ventricular fibrillation that was refractory to antiarrhythmics and defibrillation and did not survive to hospital admission.
6 CHALLENGES AND UNKNOWNS
REBOA placement carries a risk of significant vascular and ischemic injury, even in the hands of experienced physicians. In a large prospective trial of REBOA for traumatically injured patients at level 1 trauma centers in the United States, outcomes were favorable.20 Aortic occlusion was obtained in an average of 6.6 minutes, there was a low complication rate (2.2% pseudoaneurysm and 4.3% distal embolism), and REBOA had a similar survival rate to more invasive surgical techniques.20 Several additional retrospective trials have shown improvement in mortality with REBOA with low complication rates.6, 46, 47
Other large retrospective trials have shown poorer outcomes with REBOA. In 2019 Bellal et al published a large, multicentered, retrospective analysis of case‐matched outcomes involving REBOA in traumatically injured patients.48 They found increased overall mortality (REBOA 35%, no REBOA 18.9%), increased risk of acute kidney injury (REBOA 10.7%, no REBOA 3.2%), and higher rates of lower extremity amputation (REBOA 3.6%, no REBOA 0.7%). There were no significant differences in hospital length of stay, intensive care unit length of stay, or transfusion requirements at 4 or 24 hours.48 Furthermore, in 2 large retrospective reviews of Japanese trauma literature from 2015 and 2016, mortality was higher for the patients who received REBOA.49, 50 Given the vast differences between trauma patients and those with NTCA, it remains difficult to clinically contextualize the results of these studies until researchers gain more experience with this patient population.
A recent case report from Gerard et al details the complication of REBOA balloon rupture after the initiation of CPR.51 It is unknown if balloon rupture is caused by damage during insertion, would be worse with mechanical CPR devices, or if zone placement (1a‐1c) affects balloon rupture. The true frequency of balloon rupture during CPR is unknown but likely is low, as it is not reported elsewhere in the literature.
Currently, there is no evidence‐based guideline to inform balloon deflation. The accepted practice during use for hemorrhage control, which is based on expert opinion, is to deflate the balloon as tolerated by proximal aortic physiology. A similar approach should be rapidly followed when ROSC is obtained, in order to limit potentially deleterious increases in cardiac afterload on an already stunned myocardium. A variety of procedures have been used in animal models, involving reducing the balloon slowly over a period of 30 to 60 seconds.52
The variability in response to REBOA during cardiac arrest, seen in both laboratory studies and the Norwegian out‐of‐hospital clinical study, does not presently have a clear explanation. REBOA may augment CPP during cardiac arrest, but the primary driver of blood flow is providing high‐quality chest compressions. Factors, such as downtime before CPR, body habitus, CPR quality, volume status, and upper body peripheral arterial vasomotor tone, may significantly influence the effect of REBOA during CPR. This variance and its effect on outcomes need further investigation.
7 THE FUTURE OF CARDIAC ARREST
REBOA is being investigated to treat NTCA along with other advanced technologies, including selective aortic arch perfusion (SAAP) and ECMO. SAAP utilizes a large‐lumen balloon catheter to occlude the thoracic aorta and provide heart and brain perfusion during cardiac arrest.53, 54 Although the SAAP catheter, like REBOA catheter, is inserted via a femoral artery to the thoracic aorta, SAAP is primarily an extracorporeal perfusion intervention. After aortic occlusion is obtained, an external pump infuses oxygenated perfusate into the aortic arch in to improve oxygen delivery to critical organs. Thus, SAAP has more in common with ECMO than REBOA. Aortic occlusion with SAAP is primarily to direct perfusate flow preferentially to the heart and brain to promote ROSC and favorable neurological recovery, respectively. Laboratory models of both ventricular fibrillation and hemorrhage‐induced cardiac arrest have shown high rates of ROSC.53 SAAP is presently undergoing regulatory review for clinical trial initiation.
ECMO has been used to treat refractory cardiac arrest since the 1980s.55 Although ECMO is primarily used in the pediatric population, its use for extracorporeal cardiopulmonary resuscitation (ECPR) has expanded in recent years. In a large retrospective trial of ECMO in NTCA, survival to hospital discharge was an impressive 29%.56 Although these results are promising, none of the studies involving ECMO in NTCA have utilized a prospective control group, making it difficult to determine the efficacy of this intervention. ECMO is resource intensive, associated with significant cost and requires multispecialty expertise for placement and management.57 Recent literature suggests ECMO may be cost effective,58 but it is not yet generalizable to most community EDs where the majority of cardiac arrests are treated. REBOA, by contrast, is lower cost and requires a skillset already mastered by emergency physicians. As demonstrated by Brede and Coniglio et al, REBOA may have a role in bridging patients to more advanced interventions such as ECMO,19 an intra‐aortic balloon pump,45 or cardiac catheterization.
8 CONCLUSION
REBOA is a novel technique for the management of NTCA. Work with animal models has shown that REBOA placement improves CPP and cerebral perfusion pressure and leads to increased rates of ROSC. Early feasibility human trials have shown promise and Phase 1 trials for REBOA in NTCA are currently underway. Unlike more resource‐intensive interventions, REBOA is relatively low cost and requires a technical skillset that most emergency physicians have already mastered, making its widespread dissemination more feasible. REBOA for NTCA remains in its infancy and numerous questions remain about its feasibility, efficacy, and safety. If aortic occlusion with REBOA for NTCA is demonstrated to be effective in humans, the potential for change in clinical practice and improvement in quality of life is substantial.
ACKNOWLEDGMENTS
None.
AUTHOR CONTRIBUTIONS
Study concept and design (Craig D. Nowadly, M. Austin Johnson, James I. Daley); drafting of the manuscript (Craig D. Nowadly, M. Austin Johnson, Guillaume L. Hoareau, James E Manning,James I. Daley); critical revision of the manuscript (Craig D. Nowadly, M. Austin Johnson, Guillaume L. Hoareau, James E Manning, James I. Daley); and approval of final manuscript (Craig D. Nowadly, M. Austin Johnson, Guillaume L. Hoareau, James E Manning, James I. Daley).
CONFLICTS OF INTEREST
Craig D. Nowadly. reports no conflict of interest. M. Austin Johnson. is a founder and stockholder of Certus Critical Care, Inc. Guillaume L. Hoareau. reports no conflict of interest. James E. Manning. is a co‐founder and stockholder of Resusitech, Inc. James I. Daley has received grant funding from Prytime Medical Devices Inc. and the American Heart Association.
DISCLAIMERS
この資料に示されている見解は著者の見解であり、米国政府、国防総省、または空軍省の公式の方針または立場を反映していません。