Dexmedetomidine and Outcomes of Elderly Admitted to ICU After Surgery

Impact of Low-dose Dexmedetomidine on Outcomes of Elderly Admitted to ICU After Noncardiac Surgery: a Randomized Controlled Trial

Sleep disorder and delirium are common problems in intensive care unit (ICU) patients, and may lead to poor prognosis. The investigators' previous study showed that nighttime infusion of low-dose dexmedetomidine improved the sleep quality and decreased the incidence of delirium in ICU patients after surgery. Long-term follow-up of these patients showed that low-dose dexmedetomidine also improved 2-year survival and the quality of life in 3-year survivors. The purpose of this study is to investigate the effect of low-dose dexmedetomidine on the long-term outcome of elderly patients admitted to the ICU after noncardiac surgery.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic and anti-anxiety properties. Unlike other sedative agents, dexmedetomidine exerts its sedative effects through an endogenous sleep-promoting pathway, producing a state like non-rapid eye movement sleep. For mechanically ventilated patients, sedative-dose dexmedetomidine infusion at night maintains circadian rhythm, increases sleep efficiency, and improves sleep architecture. When used for sedation in mechanical ventilated patients, it reduces the incidence of delirium.

Dexmedetomidine may improve patient outcomes by improving sleep quality. A previous randomized trial found that, for elderly patients who were admitted to ICU after noncardiac surgery, nighttime infusion of low-dose dexmedetomidine significantly improves the sleep quality and decreases the incidence of postoperative delirium. A long-term follow-up of these patients showed that low-dose dexmedetomidine infusion significantly increased survival up to 2 years, and improved cognitive function and quality of life in 3-year survivors.

In the study mentioned above, dexmedetomidine was only infused during the night after surgery with a fixed dose. The investigators hypothesize that, for elderly admitted to ICU after surgery, nighttime infusion of individualized low-dose dexmedetomidine may improve long-term outcomes. This randomized controlled trial is designed to investigate the effect of low-dose dexmedetomidine on 1-year survival and the quality of life of 1-year survivors in elderly patients admitted to the ICU after surgery.

Inclusion Criteria:

• Age ≥65 years old;
• Admitted to intensive care unit (ICU) after noncardiac surgery;
• Expected to stay in ICU until the next morning. For those with endotracheal intubation, the expected duration of mechanical ventilation is <24 hours;
• Provide written informed consents.

Exclusion Criteria:

• Preoperative history of schizophrenia, epilepsy, Parkinsonism, or myasthenia gravis;
• Inability to communicate in the preoperative period (coma, profound dementia, or language barrier);
• Preoperative history of sleep apnea (previous diagnosis; or STOP-Bang score ≥3 with serum bicarbonate ≥ 28 mmol/L);
• Known sick sinus syndrome, severe sinus bradycardia (<50 beats per min [bpm]), or second degree or higher atrioventricular block without pacemaker;
• Hypotension (systolic blood pressure [SBP] <90 mmHg, mean arterial pressure [MAP] <70 mmHg, or a decrease of SBP >30% of baseline) or in a state of shock (vasopressors are required to maintain MAP ≥65 mmHg and serum lactate >2 mmol/L);
• Severe hepatic dysfunction (Child-Pugh class C), renal failure (requirement of renal replacement therapy), or expected survival <24 hours;
• Traumatic brain injury or neurosurgery;
• Presence of delirium before surgery (assessed with Confusion Assessment Method [CAM]/CAM-ICU);
• Undergoing treatment of dexmedetomidine or clonidine;
• Other conditions that are considered unsuitable for study participation.