Dexmedetomidine and Delirium in Patients After Cardiac Surgery

Peking University

Status and phase: Completed; Phase 4

Conditions: C.Surgical Procedure; Cardiac; Postoperative Complications; Delirium

Treatments: Drug: 0.9% sodium chloride for injection; Drug: dexmedetomidine hydrochloride for injection

Study type: Interventional

Funder types: Other

Identifiers

NCT02267538

PekingUFH

Details and patient eligibility

About

Postoperative delirium (POD) is a frequently occurring complication after cardiac surgery. Its occurrence is associated with worse outcomes of patients, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. It is also associated with long-term cognitive decline and decreased quality of life. However, until recently, pharmacological interventions that can effectively prevent its occurrence are still limited. The purpose of this study is to investigate whether perioperative dexmedetomidine use can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery.

Full description

Delirium is a state of global cerebral dysfunction manifested by acute disturbance of consciousness, attention, cognition and perception. It develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. The reported incidences of delirium after cardiac surgery varied from 21% to 47%. The occurrence of postoperative delirium has significant harmful effects on patients' outcomes, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. Its occurrence is also associated with long-term cognitive decline and decreased quality of life.

The exact pathogenesis that lead to the occurrence of POD are still unclear, and possibly involves mechanisms such as inflammation, pain and sleep deprivation after surgery. Furthermore, it has been shown that anesthesia management might also have exerted some effects. Studies found that avoidance of unnecessary deep anesthesia (under the guidance of Bispectral Index monitoring) decreases the incidence of POD. Theoretically, measures that decreases the requirement of anesthetics while maintaining adequate depth of anesthesia and those that alleviates inflammation and improves postoperative analgesia as well as sleep quality will decrease the incidence of POD.

Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonists that provides anxiolysis, sedation and modest analgesia with minimal respiratory depression. Studies showed that, when used as an adjunctive anesthetics, dexmedetomidine significantly decreases the requirement of opioid analgesics and other sedatives during anesthesia. A recent study of our group found that continuous infusion of low-dose dexmedetomidine (0.2 ug/kg/h) during the first night after surgery significantly improved subjective sleep quality. Two randomized controlled trials found that, when compared with traditional sedatives (midazolam and propofol) and analgesics (such as morphine), use of dexmedetomidine in patients after cardiac surgery is associated with decreased risk of delirium. However, questions still exist as to whether dexmedetomidine prevent delirium or just does not increase its occurrence since traditional sedatives/analgesics themselves increases the risk of delirium. Furthermore, animal experiments showed that dexmedetomidine inhibits the degree of inflammation induced by endotoxins.

The investigators hypothesize that use of dexmedetomidine as an adjunctive agent during the perioperative period can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery, possibly by decreasing the requirement of anesthetics during surgery, by ameliorating analgesia as well as sleep quality after surgery, and by alleviating the degree of perioperative inflammatory response.

Enrollment: 285 patients

Sex: All

Ages: 60 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patients of 60 years or older who are planning to receive cardiac surgery (CABG and/or valve replacement surgery)

Exclusion criteria

Patients will be excluded if they meet any of the following criteria:

1. Refuse to participate;
2. Preoperative history of schizophrenia, epilepsia, Parkinson syndrome, or severe dementia;
3. Inability to communicate in the preoperative period because of severe visual/auditory dysfunction or language barrier;
4. History of brain injury or neurosurgery;
5. Preoperative sick sinus syndrome, severe bradycardia (HR < 50 bpm), second-degree or above atrioventricular block without pacemaker;
6. Severe hepatic dysfunction (Child-Pugh class C);
7. Severe renal dysfunction (requirement of renal replacement therapy);
8. Other conditions that are considered unsuitable for participation.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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285 participants in 2 patient groups, including a placebo group

Dex group

Experimental group

Description:

The intervention drug (dexmedetomidine hydrochloride for injection) will be administered during a period from before anesthesia induction until the end of mechanical ventilation after surgery.

Treatment:

Drug: dexmedetomidine hydrochloride for injection

Placebo group

Placebo Comparator group

Description:

The placebo drug (normal saline, i.e., 0.9% sodium chloride for injection) will be administered in the same way and rate for a same duration as that in the Dex group.

Treatment:

Drug: 0.9% sodium chloride for injection