PDF(Pubmed)
Abstract：
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.
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.
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.
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.
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.
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.
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：
氟哌啶醇,一种广泛使用的抗精神病药，已被认为对COVID-19患者可能有用，原因是其对SARS-CoV-2的体外抗病毒作用，可能是通过sigma-1受体拮抗剂作用。
我们研究了在巴黎大巴黎大学援助公共医院（AP-HP）因COVID-19住院的成年患者中，氟哌啶醇的使用与插管或死亡以及出院时间的关系。研究基线定义为入院日期。在事件发生时间分析中，主要终点是插管或死亡的复合终点，次要终点是幸存者出院回家。在初步分析中，我们使用单变量Cox回归模型,在基于患者特征和其他精神药物的匹配分析样本中,比较了接受和未接受氟哌啶醇的患者的这两种结局.敏感性分析包括具有逆概率加权的倾向评分分析和多变量Cox回归模型。
在15121名COVID-19PT-PCR检测阳性的成人住院患者中，39例患者（0.03％）在入院的前48小时内接受了氟哌啶醇。平均随访13.8天（SD=17.9），在5月1日研究结束时，2,024例患者（13.4%）发生了主要终点事件，10,179例患者（77.6%）出院。主要终点发生在接受氟哌啶醇的9例患者（23.1％）和未接受氟哌啶醇的2,015例患者（13.4％）。出院回家的次要终点发生在接受氟哌啶醇的16例患者（61.5%）和未接受氟哌啶醇的9,907例患者（85.8%）。氟哌啶醇的使用与原发性(HR，0.80；95%CI，0.39至1.62，p=0.531)和次要(HR，1.30；95%CI，0.74至2.28，p=0.355)终点。多重敏感性分析结果相似。
这项多中心观察研究的结果表明，氟哌啶醇的平均剂量为每天4.5mg（SD=5.2），平均持续时间为8.4天（SD=7.2），可能与插管或死亡风险无关。或者有时间回家，在因COVID-19住院的成年患者中。
我们研究了在巴黎大巴黎大学援助公共医院（AP-HP）因COVID-19住院的成年患者中，氟哌啶醇的使用与插管或死亡以及出院时间的关系。研究基线定义为入院日期。在事件发生时间分析中，主要终点是插管或死亡的复合终点，次要终点是幸存者出院回家。在初步分析中，我们使用单变量Cox回归模型,在基于患者特征和其他精神药物的匹配分析样本中,比较了接受和未接受氟哌啶醇的患者的这两种结局.敏感性分析包括具有逆概率加权的倾向评分分析和多变量Cox回归模型。
在15121名COVID-19PT-PCR检测阳性的成人住院患者中，39例患者（0.03％）在入院的前48小时内接受了氟哌啶醇。平均随访13.8天（SD=17.9），在5月1日研究结束时，2,024例患者（13.4%）发生了主要终点事件，10,179例患者（77.6%）出院。主要终点发生在接受氟哌啶醇的9例患者（23.1％）和未接受氟哌啶醇的2,015例患者（13.4％）。出院回家的次要终点发生在接受氟哌啶醇的16例患者（61.5%）和未接受氟哌啶醇的9,907例患者（85.8%）。氟哌啶醇的使用与原发性(HR，0.80；95%CI，0.39至1.62，p=0.531)和次要(HR，1.30；95%CI，0.74至2.28，p=0.355)终点。多重敏感性分析结果相似。
这项多中心观察研究的结果表明，氟哌啶醇的平均剂量为每天4.5mg（SD=5.2），平均持续时间为8.4天（SD=7.2），可能与插管或死亡风险无关。或者有时间回家，在因COVID-19住院的成年患者中。
