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COVID-19 住院患者中氟哌啶醇的观察性研究。

Observational study of haloperidol in hospitalized patients with COVID-19.

机构信息

Département de Psychiatrie, Hôpital Corentin-Celton, Centre Université de Paris, AP-HP, Issy-les-Moulineaux, France.

INSERM, Institut de Psychiatrie et Neurosciences de Paris, Paris, France.

出版信息

PLoS One. 2021 Feb 19;16(2):e0247122. doi: 10.1371/journal.pone.0247122. eCollection 2021.

Abstract

BACKGROUND

Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect.

METHODS

We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models.

RESULTS

Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses.

CONCLUSION

Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

摘要

背景

氟哌啶醇是一种广泛使用的抗精神病药,由于其对 SARS-CoV-2 的体外抗病毒作用,可能通过 sigma-1 受体拮抗剂作用,被认为对 COVID-19 患者可能有用。

方法

我们研究了在巴黎公立医院集团(AP-HP)大巴黎大学附属医院住院的 COVID-19 成年患者中,氟哌啶醇的使用与插管或死亡以及出院回家时间之间的关联。研究的基线定义为入院日期。主要终点是插管或死亡的复合终点,次要终点是幸存者在时间到事件分析中的出院回家。在主要分析中,我们在基于患者特征和其他精神药物的匹配分析样本中,使用单变量 Cox 回归模型比较了接受和未接受氟哌啶醇的患者这两个结局。敏感性分析包括使用逆概率加权的倾向评分分析和多变量 Cox 回归模型。

结果

在 15121 名接受过 COVID-19 阳性 PCR 检测的成年住院患者中,有 39 名患者(0.03%)在入院的头 48 小时内接受了氟哌啶醇治疗。在平均 13.8 天(SD=17.9)的随访期间,2024 名患者(13.4%)发生了主要终点事件,在研究结束时的 5 月 1 日,有 10179 名患者(77.6%)出院回家。接受氟哌啶醇治疗的 9 名患者(23.1%)发生了主要终点事件,而未接受氟哌啶醇治疗的 2015 名患者(13.4%)发生了该事件。接受氟哌啶醇治疗的 16 名患者(61.5%)出院回家,而未接受氟哌啶醇治疗的 9907 名患者(85.8%)出院回家。氟哌啶醇的使用与主要终点(HR,0.80;95%CI,0.39 至 1.62,p=0.531)和次要终点(HR,1.30;95%CI,0.74 至 2.28,p=0.355)均无显著关联。多项敏感性分析结果相似。

结论

这项多中心观察性研究的结果表明,在 COVID-19 住院成年患者中,平均每天处方 4.5 毫克(SD=5.2)的氟哌啶醇(SD=7.2),平均持续 8.4 天(SD=7.2),可能与插管或死亡风险以及出院回家时间无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba8f/7895415/397ddd6f72b5/pone.0247122.g001.jpg

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