Andersen-Ranberg Nina C, Poulsen Lone M, Perner Anders, Wetterslev Jørn, Estrup Stine, Hästbacka Johanna, Morgan Matt, Citerio Giuseppe, Caballero Jesus, Lange Theis, Kjær Maj-Brit N, Ebdrup Bjørn H, Engstrøm Janus, Olsen Markus H, Oxenbøll Collet Marie, Mortensen Camilla B, Weber Sven-Olaf, Andreasen A Sofie, Bestle Morten H, Uslu Bülent, Scharling Pedersen Helle, Gramstrup Nielsen Louise, Toft Boesen Hans C, Jensen Jacob V, Nebrich Lars, La Cour Kirstine, Laigaard Jens, Haurum Cecilie, Olesen Marie W, Overgaard-Steensen Christian, Westergaard Bo, Brand Björn, Kingo Vesterlund Gitte, Thornberg Kyhnauv Pernille, Mikkelsen Vibe S, Hyttel-Sørensen Simon, de Haas Inge, Aagaard Søren R, Nielsen Line O, Eriksen Anne S, Rasmussen Bodil S, Brix Helene, Hildebrandt Thomas, Schønemann-Lund Martin, Fjeldsøe-Nielsen Hans, Kuivalainen Anna-Maria, Mathiesen Ole
From the Department of Anesthesiology and Intensive Care, Zealand University Hospital, Køge (N.C.A.-R., L.M.P., S.E., C.B.M., H.C.T.B., J.V.J., C.H., L.N., K.L.C., J.L., O.M.), the Departments of Intensive Care (A.P., M.-B.N.K., M.O.C., M.W.O., C.O.-S., B.W., B.B., G.K.V., P.T.K., V.S.M., S.H.-S.) and Neuroanesthesiology (M.H.O.), Copenhagen University Hospital-Rigshospitalet, the Copenhagen Trial Unit, Center for Clinical Intervention Research (J.W., J.E.), and the Section of Biostatistics, Copenhagen University (T.L.), Copenhagen, the Center for Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Glostrup (B.H.E.), Aalborg University Hospital, Aalborg University, Aalborg (S.-O.W., I.D.H., S.R.A., L.O.N., A.S.E., B.S.R.), the Department of Intensive Care, Copenhagen University Hospital, Herlev Hospital, Herlev (A.S.A., H.B.), Copenhagen University Hospital-North Zealand, Hillerød (M.H.B., M.S.-L.), Zealand University Hospital, Roskilde (B.U., T.H.), Nykøbing Falster Hospital, Nykøbing Falster (H.S.P., H.F.-N.), and Odense University Hospital, University of Southern Denmark, Odense (L.G.N.) - all in Denmark; Helsinki University Hospital, Helsinki (J.H., A.-M.K.); University Hospital of Wales, Cardiff, United Kingdom (M.M.); the Department of Medicine and Surgery, University Milano-Bicocca, Milan (G.C.); and University Hospital Arnau de Vilanova, Leida, Spain (J.C.).
N Engl J Med. 2022 Dec 29;387(26):2425-2435. doi: 10.1056/NEJMoa2211868. Epub 2022 Oct 26.
Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited.
In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization.
A total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7.0) (P = 0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group.
Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.).
氟哌啶醇常用于治疗重症监护病房（ICU）患者的谵妄，但关于其疗效的证据有限。
在这项多中心、双盲、安慰剂对照试验中，我们将因急性病入住ICU且患有谵妄的成年患者随机分配，使其接受静脉注射氟哌啶醇（每日3次，每次2.5mg，必要时额外追加2.5mg，最大日剂量总计20mg）或安慰剂。只要谵妄持续，就在ICU中给予氟哌啶醇或安慰剂，并在复发时按需给药。主要结局是随机分组后90天时存活且出院的天数。
共有1000例患者接受随机分组；510例被分配至氟哌啶醇组，490例被分配至安慰剂组。在这些患者中，987例（98.7%）纳入最终分析（氟哌啶醇组501例，安慰剂组486例）。963例患者（97.6%）可获得主要结局数据。90天时，氟哌啶醇组存活且出院的平均天数为35.8天（95%置信区间[CI]，32.9至38.6），安慰剂组为32.9天（95%CI，29.9至35.8），调整后的平均差值为2.9天（95%CI，-1.2至7.0）（P = 0.22）。90天时氟哌啶醇组的死亡率为36.3%，安慰剂组为43.3%（调整后的绝对差值为-6.9个百分点[95%CI，-13.0至-0.6]）。氟哌啶醇组有11例患者出现严重不良反应，安慰剂组有九例患者出现严重不良反应。
在ICU中患有谵妄的患者中，与安慰剂相比，氟哌啶醇治疗在90天时并未使存活且出院的天数显著增加。（由丹麦创新基金等资助；AID-ICU ClinicalTrials.gov编号，NCT03392376；欧盟临床试验编号，2017-003829-15。）
