Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial

Abstract

Background After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. Methods Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. Results A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. Conclusion In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Mapping Theme Trends and Research Frontiers in Dexmedetomidine Over Past Decade: A Bibliometric Analysis

“… 21 Overall, the results of clinical studies and meta-analyses have not provided strong support for the use of dexmedetomidine in preventing delirium in patients undergoing cardiac or non-cardiac surgery. 72–75 These findings emphasize the importance of medication timing in dexmedetomidine research.…”

“…Furthermore, large clinical trials such as DEXACET, DECADE, DESIRE, EXACTUM, and DIRECT trial have yielded conflicting results, demonstrating that dexmedetomidine did not reduce, and even increased, the incidence of postoperative delirium. 19 , 21 , 63 , 71 , 72 At the same time, Deiner et al 20 conducted a randomized controlled trial involving 404 elderly patients undergoing non-cardiac surgery and found that continuous perioperative and postoperative infusion of dexmedetomidine did not reduce the incidence of postoperative delirium. Likewise, dexmedetomidine did not decrease the risk of postoperative atrial arrhythmias or delirium in patients undergoing cardiac surgery.…”

Dexmedetomidina: Um Fármaco Versátil da Anestesia Moderna

“…4 O delirium pósoperatório é caracterizado por um início agudo de alterações do estado mental com desatenção flutuante, pensamento desorganizado e alteração do nível de consciência. 5 Uma metanálise foi utilizada para comparar a incidência de delirium pós-operatório entre quatro sedativos: sevoflurano, propofol, dexmedetomidina e midazolam. Huang e colaboradores relataram que a incidência de delirium pós-operatório com dexmedetomidina foi menor do que com placebo, propofol, sevoflurano e midazolam, independentemente do tempo de extubação ter sido maior que 1 ou 5 horas, ou se a cirurgia foi cardíaca ou não cardíaca.…”

“…Diminui o fluxo simpático do sistema nervoso central (SNC) de maneira dose-dependente e possui efeitos analgésicos melhor descritos como poupadores de opioides. 3 Existem alguns trabalhos associando o uso da dexmedetomidina à prevenção de delirium pós-operatório, [4][5][6][7] prolongamento no tempo da analgesia em bloqueios periféricos com redução pós-operatória do consumo de opioides, 8 melhora no período da extubação, 9 possível fator de proteção sobre a depressão pós-parto em gestantes com diagnóstico prévio de depressão no pré-natal, 10 possível impacto positivo no processo de recuperação intestinal pós-operatório, 11 medicação adequada para procedimentos cirúrgicos que requeiram colaboração do paciente. 12 Farmacocinética (Figura 1) A p ó s i n j e ç ã o i n t r a v e n o s a ( I V ) , a dexmedetomidina tem início de ação após aproximadamente 15 minutos.…”