小児急性呼吸窮迫症候群の小児における早期の神経筋遮断

Early Neuromuscular Blockade in Children with Pediatric Acute Respiratory Distress Syndrome.

• Surabhi Chandra
• Sahil Goel
• Ritika Dawra

抄録

小児急性呼吸窮迫症候群（PARDS）は死亡率の高い難病である。これまでARDSの管理における神経筋遮断薬の役割は議論の的となってきたが、本研究は小児急性呼吸窮迫症候群（PARDS）患者における神経筋遮断薬の役割と、関連する合併症がある場合にはその発症を検討することを目的として行われた。本研究は、第三次医療教育病院の小児集中治療室（PICU）で24ヶ月間実施されたプロスペクティブな症例対照研究です。入院中にPARDSを発症した1歳から18歳までの患者を対象に、保護者から書面によるインフォームドコンセントを得た上で対象としました。侵襲的機械的人工呼吸を必要とするPARDS患者を症例群と対照群に分けた。症例群では，ミダゾラム（1μg/kg/min）およびベクロニウム（1μg/kg/min）を用いて鎮静および麻痺を行い，最終的な管理を行った．対照群の患者には、最終的な治療と支持療法が行われたが、神経筋ブロック剤（NMBA）は投与されなかった。すべての患者は、入院中の全期間および退院後3ヵ月までの間、ミオパチーまたは神経障害の徴候や症状について追跡調査を受けた。研究期間中、613人の患者がPICUに入院し、そのうち91人の患者がPARDSの対象となった。PARDS患者91人中67人（73.6％）の主な病因は敗血症でした。本研究には59名の患者が含まれ、そのうち29名が症例群、30名が対照群に含まれていました。症例群29例中、25例（86.2％）が気管切開に成功した。症例群では4名が気絶したが，対照群では30名中14名（46.7％）が気絶した．症例群26例（89.6％）に低血圧が認められたが，そのすべてが治療終了後48時間以内に消失した．低血圧が消失するまでの平均時間は症例群で41.6時間（標準偏差[SD]：5.759；範囲：24～48）であり，生存していた低血圧の対照群10例の平均消失時間103時間（SD：18.995；範囲：90～126）よりも有意に短かった（<0.0001）。ベクロニウム治療48時間後の平均酸素化指数（OI）は、症例群の入院時の平均酸素化指数（OI）よりも有意に低かった（<0.0001；95％信頼区間：5.9129-9.9671）。ベクロニウム投与を受けた患者では、入院中、退院時、退院後3ヵ月までの追跡評価で神経筋障害を示した患者はいなかった。本研究では、PARDSと診断され、機械換気とベクロニウム療法で管理された小児症例では、対照群と比較して、48時間のNMBA療法後の平均起立耐性は改善し、死亡率は低かった。これらの患者ではNMBAに関連した脱力の発生率は一般的には認められなかった。

Pediatric acute respiratory distress syndrome (PARDS) is a challenging problem with high mortality. Role of neuromuscular blockade in the management of ARDS to date has been controversial, and this study was done to study the role of neuromuscular blockade in children having PARDS and development of associated complications, if any. This was a prospective, case-control study conducted in the pediatric intensive care unit (PICU) of a tertiary care teaching hospital, over a period of 24 months. Patients of age 1 to 18 years who presented with or developed PARDS during their course of hospitalization were included after written informed consent was obtained from their parents and/or guardians. Patients with PARDS requiring invasive mechanical ventilation were partitioned into a case group and a control group. Case group patients were sedated and paralyzed using midazolam (1 µg/kg/min) and vecuronium (1 µg/kg/min), respectively, along with institution of definitive management. Control group patients were given definitive and supportive therapy, but no neuromuscular blocking agents (NMBAs). All patients were followed up for signs and symptoms of myopathy or neuropathy during the entire duration of hospital stay and up to 3 months after discharge. During the study period, 613 patients were admitted to the PICU of which 91 patients qualified as having PARDS. Sepsis was the main etiology in 67 of the 91 patients (73.6%) with PARDS. Fifty-nine patients were included in the study, of which 29 patients were included in the case group and 30 patients were included in the control group. Among the 29 case group patients, 25 patients (86.2%) were successfully extubated. Four patients from the case group expired, while 14 out of 30 control group patients (46.7%) expired. Hypotension was present in 26 case group patients (89.6%), of which all showed resolution within 48 hours of definitive treatment. The mean time to resolution of hypotension was 41.6 hours (standard deviation [SD]: 5.759; range: 24-48) for case group patients, significantly lower (  < 0.0001) than the mean time to resolution of 103 hours (SD: 18.995; range: 90-126) for the 10 control group patients with hypotension that survived. Mean oxygenation index (OI) following 48 hours of vecuronium therapy was significantly lower (  < 0.0001; 95% confidence interval: 5.9129-9.9671) than mean OI at admission for case group patients. None of the patients receiving vecuronium exhibited neuromuscular deficit during their hospital stay, at time of discharge, or at follow-up evaluation up to 3 months after discharge. In this study, pediatric cases diagnosed with PARDS and managed with mechanical ventilation and vecuronium therapy had improved mean OI following 48 hours of NMBA therapy and a lower mortality when compared with matched control group patients. Incidence of NMBA-related weakness was not commonly observed in these patients.

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