Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial
BACKGROUND: The delirium-sparing effect of nighttime dexmedetomidine has not been studied after surgery. We hypothesised that a nighttime dose of dexmedetomidine would reduce the incidence of postoperative delirium as compared to placebo. METHODS: This single-centre, parallel-arm, randomised, placeb...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2023
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| Online Access: | https://hdl.handle.net/1721.1/148700 |
| _version_ | 1811073630269865984 |
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| author | Qu, Jason Z Mueller, Ariel McKay, Tina B Westover, M Brandon Shelton, Kenneth T Shaefi, Shahzad D'Alessandro, David A Berra, Lorenzo Brown, Emery N Houle, Timothy T Akeju, Oluwaseun |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Qu, Jason Z Mueller, Ariel McKay, Tina B Westover, M Brandon Shelton, Kenneth T Shaefi, Shahzad D'Alessandro, David A Berra, Lorenzo Brown, Emery N Houle, Timothy T Akeju, Oluwaseun |
| author_sort | Qu, Jason Z |
| collection | MIT |
| description | BACKGROUND: The delirium-sparing effect of nighttime dexmedetomidine has not been studied after surgery. We hypothesised that a nighttime dose of dexmedetomidine would reduce the incidence of postoperative delirium as compared to placebo. METHODS: This single-centre, parallel-arm, randomised, placebo-controlled superiority trial evaluated whether a short nighttime dose of intravenous dexmedetomidine (1 μg/kg over 40 min) would reduce the incidence of postoperative delirium in patients 60 years of age or older undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomised to receive dexmedetomidine or placebo in a 1:1 ratio. The primary outcome was delirium on postoperative day one. Secondary outcomes included delirium within three days of surgery, 30-, 90-, and 180-day abbreviated Montreal Cognitive Assessment scores, Patient Reported Outcome Measures Information System quality of life scores, and all-cause mortality. The study was registered as NCT02856594 on ClinicalTrials.gov on August 5, 2016, before the enrolment of any participants. FINDINGS: Of 469 patients that underwent randomisation to placebo (n = 235) or dexmedetomidine (n = 234), 75 met a prespecified drop criterion before the study intervention. Thus, 394 participants (188 dexmedetomidine; 206 placebo) were analysed in the modified intention-to-treat cohort (median age 69 [IQR 64, 74] years; 73.1% male [n = 288]; 26·9% female [n = 106]). Postoperative delirium status on day one was missing for 30 (7.6%) patients. Among those in whom it could be assessed, the primary outcome occurred in 5 of 175 patients (2.9%) in the dexmedetomidine group and 16 of 189 patients (8.5%) in the placebo group (OR 0.32, 95% CI: 0.10-0.83; P = 0.029). A non-significant but higher proportion of participants experienced delirium within three days postoperatively in the placebo group (25/177; 14.1%) compared to the dexmedetomidine group (14/160; 8.8%; OR 0.58; 95% CI, 0.28-1.15). No significant differences between groups were observed in secondary outcomes or safety. INTERPRETATION: Our findings suggested that in elderly cardiac surgery patients with a low baseline risk of postoperative delirium and extubated within 12 h of ICU admission, a short nighttime dose of dexmedetomidine decreased the incidence of delirium on postoperative day one. Although non-statistically significant, our findings also suggested a clinical meaningful difference in the three-day incidence of postoperative delirium. FUNDING: National Institute on Aging (R01AG053582). |
| first_indexed | 2024-09-23T09:36:01Z |
| format | Article |
| id | mit-1721.1/148700 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:36:01Z |
| publishDate | 2023 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1487002023-03-25T03:43:50Z Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial Qu, Jason Z Mueller, Ariel McKay, Tina B Westover, M Brandon Shelton, Kenneth T Shaefi, Shahzad D'Alessandro, David A Berra, Lorenzo Brown, Emery N Houle, Timothy T Akeju, Oluwaseun Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences BACKGROUND: The delirium-sparing effect of nighttime dexmedetomidine has not been studied after surgery. We hypothesised that a nighttime dose of dexmedetomidine would reduce the incidence of postoperative delirium as compared to placebo. METHODS: This single-centre, parallel-arm, randomised, placebo-controlled superiority trial evaluated whether a short nighttime dose of intravenous dexmedetomidine (1 μg/kg over 40 min) would reduce the incidence of postoperative delirium in patients 60 years of age or older undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomised to receive dexmedetomidine or placebo in a 1:1 ratio. The primary outcome was delirium on postoperative day one. Secondary outcomes included delirium within three days of surgery, 30-, 90-, and 180-day abbreviated Montreal Cognitive Assessment scores, Patient Reported Outcome Measures Information System quality of life scores, and all-cause mortality. The study was registered as NCT02856594 on ClinicalTrials.gov on August 5, 2016, before the enrolment of any participants. FINDINGS: Of 469 patients that underwent randomisation to placebo (n = 235) or dexmedetomidine (n = 234), 75 met a prespecified drop criterion before the study intervention. Thus, 394 participants (188 dexmedetomidine; 206 placebo) were analysed in the modified intention-to-treat cohort (median age 69 [IQR 64, 74] years; 73.1% male [n = 288]; 26·9% female [n = 106]). Postoperative delirium status on day one was missing for 30 (7.6%) patients. Among those in whom it could be assessed, the primary outcome occurred in 5 of 175 patients (2.9%) in the dexmedetomidine group and 16 of 189 patients (8.5%) in the placebo group (OR 0.32, 95% CI: 0.10-0.83; P = 0.029). A non-significant but higher proportion of participants experienced delirium within three days postoperatively in the placebo group (25/177; 14.1%) compared to the dexmedetomidine group (14/160; 8.8%; OR 0.58; 95% CI, 0.28-1.15). No significant differences between groups were observed in secondary outcomes or safety. INTERPRETATION: Our findings suggested that in elderly cardiac surgery patients with a low baseline risk of postoperative delirium and extubated within 12 h of ICU admission, a short nighttime dose of dexmedetomidine decreased the incidence of delirium on postoperative day one. Although non-statistically significant, our findings also suggested a clinical meaningful difference in the three-day incidence of postoperative delirium. FUNDING: National Institute on Aging (R01AG053582). 2023-03-24T14:47:38Z 2023-03-24T14:47:38Z 2023-02 2023-03-24T14:37:47Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/148700 Qu, Jason Z, Mueller, Ariel, McKay, Tina B, Westover, M Brandon, Shelton, Kenneth T et al. 2023. "Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial." eClinicalMedicine, 56. en 10.1016/j.eclinm.2022.101796 eClinicalMedicine Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Qu, Jason Z Mueller, Ariel McKay, Tina B Westover, M Brandon Shelton, Kenneth T Shaefi, Shahzad D'Alessandro, David A Berra, Lorenzo Brown, Emery N Houle, Timothy T Akeju, Oluwaseun Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial |
| title | Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial |
| title_full | Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial |
| title_fullStr | Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial |
| title_full_unstemmed | Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial |
| title_short | Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): a single-centre, parallel-arm, randomised, placebo-controlled superiority trial |
| title_sort | nighttime dexmedetomidine for delirium prevention in non mechanically ventilated patients after cardiac surgery mindds a single centre parallel arm randomised placebo controlled superiority trial |
| url | https://hdl.handle.net/1721.1/148700 |
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