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Method Article
研究における豚の使用は近年増加しています。それにもかかわらず、ブタは困難な気道解剖学的構造を特徴としています。内視鏡ガイド下気管内挿管を行う方法を実証することにより、本プロトコルは、実験動物の安全性をさらに高め、動物の苦痛や不必要な死を回避することを目的としています。
気管内挿管は、安全な気道または高い換気圧を必要とするさまざまな介入のためのブタモデルにおけるトランスレーショナル研究の基本的な要件であることがよくあります。気管内挿管は困難なスキルであり、最適な条件下で高い成功率を達成するためには、気管内挿管の成功回数を最小限に抑える必要がありますが、これは非麻酔学の研究者にとっては達成できないことがよくあります。特定のブタ気道解剖学的構造のために、困難な気道が通常想定され得る。安全な気道を確立することが不可能であると、実験動物の怪我、有害事象、または死亡につながる可能性があります。前向き無作為化制御評価アプローチを使用すると、光ファイバー支援気管内挿管には時間がかかりますが、臨床的に関連する酸素飽和度の低下を引き起こすことなく、従来の挿管よりも初回通過成功率が高いことが示されています。このモデルは、内視鏡ガイド気管内挿管の標準化されたレジメンを提示し、特に直接喉頭鏡 検査による 気管内挿管の技術に不慣れな研究者に安全な気道を提供します。この手順は、動物の苦しみと不必要な動物の損失を最小限に抑えることが期待されています。
気管内挿管は、気道の確保または高い換気圧(心肺蘇生法中の換気1や急性呼吸窮迫症候群2など)を必要とするさまざまな介入、または声門上気道装置による内部圧迫によって脳血流が損なわれないことを必要とするさまざまな介入のためのブタモデルにおけるトランスレーショナル研究の基本的な要件であることがよくあります3これは、ブタ4,5で予想される困難な気道の文脈で代替として時折伝播されます。
ブタの肺生理機能はヒトと同様の特徴を示していますが6、ブタの口腔気管解剖学的構造の特定の違いにより、気道の確保が著しく困難な場合があります7。ブタの鼻は非常に大きな舌を有する狭い開口部を有し、喉頭は非常に可動性であり、そして喉頭蓋は比較的大きく、軟口蓋まで伸びる自由端を有する。尾側では、喉頭は気管と鈍角を形成します。披裂軟骨は大きい 8.気道の最も狭い部分は声門下レベル9であり、子供の気道解剖学的構造に匹敵します10。ブタの喉頭は非常に可動性であるため、気管内チューブの端が声帯を通過するリスクがありますが、喉頭は最大数センチメートルしか尾側に変位せず、正しい挿管と間違われる可能性があります8,11。さらに、食道挿管は、ブタの気道管理を扱う際の一般的なリスクです12。
実験または早期死亡率に対応する悪影響を伴う困難または不可能な気管内挿管の割合は体系的に記録されていませんが、いくつかの症例報告が発表されています13,14。ヒトにおいて、予想外に困難な従来の挿管15の状況において可撓性挿管内視鏡を使用する可能性がある。さまざまな誤った挿管がこの措置に先行することがよくあります。これらの反復挿管の試みは、ヒトにおける有害事象と関連している16、17、特に気道合併症18。このようなイベントは、最も単純なケースでは実験の交絡変数を表すため、試験動物では有害です。最悪の場合、それらは動物の不必要な損失につながる可能性があります。
本研究では、ヒトにおいて予想される困難な気道管理のガイドラインに基づいてモデルを開発しました15、19、20、21、22、23、24。以前、同様の技術が人間の研究で光ファイバー挿管を学習するために説明されています25,26。このレポートで提示されたプロトコルは、標準化された適応が容易な挿管モデルを提供することを目的としており、気道以外の専門家がブタの気管内挿管を成功裏に安全に実行できるようにします。
このプロトコルの実験は、州および施設の動物管理委員会(ドイツ、コブレンツ、ラインラントプファルツ、承認番号G20-1-135)によって承認されました。実験はARRIVEガイドラインに従って実施した。全体として、平均体重30 kg±2 kg、12〜16週齢の麻酔をかけた雄豚10頭(Sus scrofa domestic a)が本研究に使用されました。
1.動物の準備
2.麻酔と機械的換気
3.気管内挿管
気管内挿管は、前向き無作為化対照研究設定で、10頭の雄豚(12〜16週齢、体重30 kg±3 kg)で実施されました。.ブタは2つのグループに無作為化されました:1つは従来の喉頭鏡下で挿管され(CIグループ)、もう1つのグループはプロトコルに記載されているように柔軟な挿管内視鏡 を介して 挿管支援されました(FIEグループ)。グループの割り当ては、封印された封筒を引っ張ることによって行?...
これまでの研究では、ブタモデル2,27,32,33の翻訳上の利点に関する具体的な詳細をすでに説明しています。一般に、動物のストレスレベルと不必要な痛みを減らすことは、あらゆる研究プロトコルの不可欠な部分であるべきであり、確実に再現可能なデータを生成するために最も重要です。したが...
柔軟な挿管内視鏡とその付属品は、研究目的でのみメーカーから無条件に提供されています。著者らは、これ以上の金銭的またはその他の利益相反を宣言しません。
著者は、ダグマー・ディルボンスキーの優れた技術サポートに感謝したいと思います。
Name | Company | Catalog Number | Comments |
Ambu aScope Regular | Ambu GmbH, Medizinprodukte, Bad Nauheim, Germany | Disposable fiber optic outer diameter 5 mm | |
Ambu aView Monitor | Ambu GmbH, Medizinprodukte, Bad Nauheim, Germany | monitor | |
Atracurium Hikma 50 mg/5mL | Hikma Pharma GmbH, Martinsried | atracurium | |
Azaperone (Stresnil) 40mg/mL | Lilly Deutschland GmbH, Bad Homburg, Germany | azaperone | |
BD Discardit II Spritze 2, 5, 10, 20 mL | Becton Dickinson S.A. Carretera, Mequinenza Fraga, Spain | syringe | |
BD Luer Connecta | Becton Dickinson Infusion Therapy, AB Helsingborg, Schweden | 3-way-stopcock | |
BD Microlance 3 20 G | Becton Dickinson S.A. Carretera, Mequinenza Fraga, Spain | cannula | |
Curafix i.v. classics | Lohmann & Rauscher International GmbH & Co. KG, Rengsdorf, Germany | Cannula retention dressing | |
Engström Carestation | GE Heathcare, Madison USA | ventilator | |
Fentanyl-Janssen 0.05 mg/mL | Janssen-Cilag GmbH, Neuss | fentanyl | |
Führungsstab, Durchmesser 4.3 | Rüsch | endotracheal tube introducer | |
IBM SPSS Statistics for Windows, Version 20 | IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.) | Statistical software | |
Incetomat-line 150 cm | Fresenius, Kabi Deutschland, GmbH | perfusor line | |
Intrafix Primeline | B. Braun Melsungen AG, Melsungen, Germany | Infusion line | |
JOZA Einmal Nitril Untersuchungshandschuhe | JOZA, München, Germany | disposable gloves | |
Laryngoscope, 45.48.50, KL 2000 | Medicon | Laryngoscope handle | |
Littmann Classic III Stethoscope | 3M Deutschland GmbH, Neuss, Germany | stethoscope | |
Luer Lock | B.Braun Melsungen AG, Germany | ||
Maimed Vlieskompresse | Maimed GmbH, Neuenkirchen, Germany | Fleece compress to fix the tongue | |
Masimo LNCS Adtx SpO2 sensor | Masimo Corporation Irvine, Ca 92618 USA | saturation clip for the tail | |
Masimo LNCS TC-I SpO2 ear clip sensor | Masimo Corporation Irvine, Ca 92618 USA | Saturation clip for the ear | |
Masimo Radical 7 | Masimo Corporation Irvine, Ca 92618 USA | periphereal oxygen saturation | |
Midazolam 15 mg/3 mL | Hameln Pharma GmbH, Hameln, Germany | midazolam | |
Midmark Canine Mask Small Plastic with Diaphragm FRSCM-0005 | Midmark Corp., Dayton, Ohio, USA | dog ventilation mask | |
Octeniderm farblos | Schülke & Mayr GmbH, Nordenstedt, Germany | Alcoholic disinfectant | |
Original Perfusor syringe 50 mL | B.Braun Melsungen AG, Germany | perfusor syringe | |
Perfusor FM Braun | B.Braun Melsungen AG, Germany | syringe pump | |
Propofol 2% 20 mg/mL (50 mL flasks) | Fresenius, Kabi Deutschland, GmbH | propofol | |
RÜSCH Führungsstab für Endotrachealtubus (ID 5.6 mm) | Teleflex Medical Sdn. Bhd, Malaysia | PVC coated tube guiding wire | |
Rüschelit Super Safety Clear >ID 6/6.5 /7.0 mm | Teleflex Medical Sdn. Bhd, Malaysia | endotracheal tube | |
Stainless Macintosh Größe 4 | Welch Allyn69604 | blade for laryngoscope | |
Sterofundin | B.Braun Melsungen AG, Melsungen, Germany | Balanced electrolyte solution | |
Ultrastop Antibeschlagmittel bottle with dropper 25 mL | Sigmapharm Arzneimittel GmbH, Wien, Austria | Antifog agent | |
Vasofix Safety 22 G-16 G | B.Braun Melsungen AG, Germany | venous catheter | |
VBM Cuff Manometer | VBM Medizintechnik GmbH, Sulz a.N., Germany | cuff pressure gauge | |
Zelette | Lohmann & Rauscher International GmbH & Co. KG, Rengsdorf, Germany | Tissue swab |
An erratum was issued for: Endotracheal Intubation Using a Flexible Intubation Endoscope As a Standardized Model for Safe Airway Management in Swine. The Protocol, Representative Results, and Discussion sections were updated.
In the Protocol, step 1.5 was updated from:
Disinfect the skin with a disinfectant (alcoholic) before inserting a peripheral vein cannula (22 G) into an ear vein. Spray the area, wipe once, then spray again, and allow the disinfectant to dry.
to:
Disinfect the skin with a disinfectant (alcoholic) before inserting a peripheral vein cannula (22 G) into an ear vein. Spray the area, wipe once, then spray again, and allow the disinfectant to dry. Secure the ear cannula with a band-aid (See Table of Materials).
In the Protocol, step 3.7 was updated from:
While maintaining the position of the endoscope, advance the endotracheal tube until it becomes visible in the camera image.
NOTE: If the endotracheal tube cannot be advanced through the glottic plane, there is a possibility that it has become caught on the arytenoid cartilage. In this case, the endotracheal tube must be withdrawn 1 cm and rotated by 90° before gently advancing again. If necessary, this maneuver can be repeated. Similar calibers of flexible intubation endoscope and endotracheal tube can minimize the risk of this issue occurring. If the endotracheal tube cannot be advanced despite this maneuver, it is likely that the subglottic narrowness-the narrowest part of the porcine larynx-cannot be passed. In this case, a smaller endotracheal tube size needs to be selected. Regular commercially available endotracheal tubes in sizes 6.5 cm or 7.0 cm ID should be able to pass the glottis as long as no anatomic abnormalities are present.
to:
While maintaining the position of the endoscope, advance the endotracheal tube until it becomes visible in the camera image.
NOTE: If the endotracheal tube cannot be advanced through the glottic plane, there is a possibility that it has become caught on the arytenoid cartilage. In this case, the endotracheal tube must be withdrawn 1 cm and rotated by 90° before gently advancing again. If necessary, this maneuver can be repeated. Similar calibers of flexible intubation endoscope and endotracheal tube can minimize the risk of this issue occurring. If the endotracheal tube cannot be advanced despite this maneuver, it is likely that the subglottic narrowness-the narrowest part of the porcine larynx-cannot be passed. In this case, a smaller endotracheal tube size needs to be selected. Regular commercially available endotracheal tubes in sizes 6.5 cm or 7.0 cm ID should be able to pass the glottis as long as no anatomic abnormalities are present. Endotracheal tube size requirements vary depending on the piglet size and breed.
In the Representative Results, the sixth paragraph was updated from:
Statistical analyses were performed using commercially available software (see Table of Materials). Normal distribution was examined using the Kolmogorov-Smirnoff test28. If a normal distribution was determined, group differences were analyzed using t-tests of independent samples29 or the Mann-Whitney U test30 for the non-parametric version. Data are presented as mean (± standard deviation). Correlations of ordinal-scale data were examined using Spearman's correlation coefficient31. A significance level of p < 0.05 was assumed.
to:
Statistical analyses were performed using commercially available software (see Table of Materials). Normal distribution was examined using the Kolmogorov-Smirnoff test28. If a normal distribution was determined, group differences were analyzed using t-tests of independent samples29 or the Mann-Whitney U test30 for the non-parametric version. Data are presented as mean (± standard deviation). Correlations of ordinal-scale data were examined using Spearman's correlation coefficient31. A significance level of p < 0.05 was assumed. All tests were performed with exploratory intention; therefore p-values are descriptive. Nevertheless, p < 0.05 was accepted as indicative of statistical significance.
In the Representative Results, the legend for figure 1 was updated from:
Figure 1: Number of intubation attempts in group comparison. For the group that was intubated using a flexible intubation endoscope, every intubation attempt was successful; in the group that was conventionally intubated, it took an average of 1.4 attempts before the endotracheal tube could be placed correctly. Error bars show the standard deviation. Please click here to view a larger version of this figure.
to:
Figure 1: Number of intubation attempts in group comparison. For the group that was intubated using a flexible intubation endoscope, every intubation attempt was successful; in the group that was conventionally intubated, it took an average of 1.4 attempts before the endotracheal tube could be placed correctly. Error bars show the standard deviation. n = 5 (for each group). Please click here to view a larger version of this figure.
In the Representative Results, figure 2 was updated from:
Figure 2: Time until CO2 detection in group comparison. For the group that was intubated using a flexible intubation endoscope, it took significantly longer until end-tidal CO2 could be detected, depicted as mean and standard deviation. Please click here to view a larger version of this figure.
to:
Figure 2: Time until CO2 detection in group comparison. For the group that was intubated using a flexible intubation endoscope, it took significantly longer until end-tidal CO2 could be detected, depicted as mean and standard deviation. n = 5 (for each group). Please click here to view a larger version of this figure.
In the Discussion, the fifth paragraph was updated from:
The increased duration had no clinical significance in this cohort. At no time was the termination criterion-a saturation of less than 93%-reached. This is shown in the results because a procedure change was unnecessary at any time. Prior adequate mask ventilation is a critical step to allow sufficient time for fiberoptic endotracheal tube placement to avoid rapid desaturation34. These results are consistent with previous studies comparing conventional intubation and endoscopically assisted intubations with inexperienced providers35.
to:
The increased duration had no clinical significance in this cohort. At no time was the termination criterion-a saturation of less than 93%-reached. This is shown in the results because a procedure change was unnecessary at any time. Prior adequate mask ventilation is a critical step to allow sufficient time for fiberoptic endotracheal tube placement to avoid rapid desaturation34. These results are consistent with previous studies comparing conventional intubation and endoscopically assisted intubations with inexperienced providers35. We attribute the prolonged duration of fiberoptic intubation to the fact that one must first reorient again after insertion, whereas with conventional intubation, one retains a view of the glottis. It is also important to avoid contact with the mucosa with the flexible intubation endoscope during advancement. This requires occasional corrective maneuvers. Last but not least, after successful placement, retraction of the relatively long endoscope is required, which increases the time to CO2 detection slightly.
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