Introduction

Sodium ibuprofenate in hypertonic saline (NaIHS) administered directly to the lungs by nebulization and inhalation has antibacterial and anti-inflammatory effects, with the potential to deliver these benefits to hypoxic patients. We describe a compassionate use program that offered this therapy to hospitalized COVID-19 patients.

Methods

NaIHS (50 mg ibuprofen, tid) was provided in addition to standard of care (SOC) to hospitalized COVID-19 patients until oxygen saturation levels of > 94% were achieved on ambient air. Patients wore a containment hood to diminish aerosolization. Outcome data from participating patients treated at multiple hospitals in Argentina between April 4 and October 31, 2020, are summarized. Results were compared with a retrospective contemporaneous control (CC) group of hospitalized COVID-19 patients with SOC alone during the same time frame from a subset of participating hospitals from Córdoba and Buenos Aires.

Results

The evolution of 383 patients treated with SOC + NaIHS [56 on mechanical ventilation (MV) at baseline] and 195 CC (21 on MV at baseline) are summarized. At baseline, NaIHS-treated patients had basal oxygen saturation of 90.7 ± 0.2% (74.3% were on supplemental oxygen at baseline) and a basal respiratory rate of 22.7 ± 0.3 breath/min. In the CC group, basal oxygen saturation was 92.6 ± 0.4% (52.1% were on oxygen supplementation at baseline) and respiratory rate was 19.3 ± 0.3 breath/min. Despite greater pulmonary compromise at baseline in the NaIHS-treated group, the length of treatment (LOT) was 9.1 ± 0.2 gs with an average length of stay (ALOS) of 11.5 ± 0.3 days, in comparison with an ALOS of 13.3 ± 0.9 days in the CC group. In patients on MV who received NaIHS, the ALOS was lower than in the CC group. In both NaIHS-treated groups, a rapid reversal of deterioration in oxygenation and NEWS2 scores was observed acutely after initiation of NaIHS therapy. No serious adverse events were considered related to ibuprofen therapy. Mortality was lower in both NaIHS groups compared with CC groups.

Conclusions

Treatment of COVID-19 pneumonitis with inhalational nebulized NaIHS was associated with rapid improvement in hypoxia and vital signs, with no serious adverse events attributed to therapy. Nebulized NaIHS s worthy of further study in randomized, placebo-controlled trials (ClinicalTrials.gov: NCT04382768).

中文翻译：

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在同情使用计划中通过雾化布洛芬酸钠逆转 SARS-CoV2 诱导的缺氧

介绍

通过雾化和吸入直接施用于肺部的高渗盐水 (NaIHS) 中的布洛芬酸钠具有抗菌和抗炎作用，有可能为缺氧患者带来这些益处。我们描述了一个同情使用计划，该计划为住院的 COVID-19 患者提供这种疗法。

方法

除了标准护理 (SOC) 外，还向住院的 COVID-19 患者提供 NaIHS（50 毫克布洛芬，tid），直到环境空气中的氧饱和度达到 > 94%。患者佩戴防护罩以减少雾化。总结了 2020 年 4 月 4 日至 10 月 31 日期间在阿根廷多家医院接受治疗的参与患者的结果数据。结果与来自科尔多瓦和布宜诺斯艾利斯的一部分参与医院的同一时间段内仅患有 SOC 的住院 COVID-19 患者的回顾性同期对照 (CC) 组进行了比较。

结果

总结了 383 名接受 SOC + NaIHS [56 名在基线时使用机械通气 (MV)] 和 195 名 CC（21 名在基线时使用 MV）治疗的患者的进展。在基线时，接受 NaIHS 治疗的患者的基础氧饱和度为 90.7 ± 0.2%（74.3% 的患者在基线时补充氧气）和基础呼吸频率为 22.7 ± 0.3 次/分钟。在 CC 组中，基础氧饱和度为 92.6 ± 0.4%（52.1% 为基线补充氧气），呼吸频率为 19.3 ± 0.3 次呼吸/分钟。尽管 NaIHS 治疗组在基线时肺部受损更大，但治疗时间 (LOT) 为 9.1 ± 0.2 gs，平均住院时间 (ALOS) 为 11.5 ± 0.3 天，而 ALOS 为 13.3 ± 0.9 天在CC组。在接受 NaIHS 的 MV 患者中，ALOS 低于 CC 组。在两个 NaIHS 治疗组中，开始 NaIHS 治疗后，氧合恶化和 NEWS2 评分迅速逆转。没有严重的不良事件被认为与布洛芬治疗有关。与 CC 组相比，两个 NaIHS 组的死亡率均较低。

结论

用吸入雾化 NaIHS 治疗 COVID-19 肺炎与缺氧和生命体征的快速改善相关，没有严重的不良事件归因于治疗。雾化 NaIHS 值得在随机、安慰剂对照试验中进一步研究（ClinicalTrials.gov：NCT04382768）。