Dexmedetomidine and Delirium in Patients After Cardiac Surgery
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|ClinicalTrials.gov Identifier: NCT02267538|
Recruitment Status : Completed
First Posted : October 17, 2014
Results First Posted : February 5, 2018
Last Update Posted : March 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Delirium C.Surgical Procedure; Cardiac Postoperative Complications||Drug: dexmedetomidine hydrochloride for injection Drug: 0.9% sodium chloride for injection||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||285 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Impact of Dexmedetomidine on the Incidence of Postoperative Delirium in Patients After Cardiac Surgery: a Randomized, Double-blinded, and Placebo-controlled Clinical Trial|
|Study Start Date :||November 2014|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||November 2015|
Experimental: Dex group
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.
Drug: dexmedetomidine hydrochloride for injection
Before anesthesia, dexmedetomidine hydrochloride for injection (200 ug/2 ml) will be diluted with normal saline to 50 ml (final dexmedetomidine concentration 4 ug/ml).
Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes (i.e., dexmedetomidine 0.6 μg/kg in 10 minutes), followed by continuous infusion at a rate of [0.1*kg] ml/h (i.e., dexmedetomidine at a rate of 0.4 μg /kg/h) until the end of surgery.
At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h (i.e., dexmedetomidine at a rate of 0.1 ug/kg/h) and continued until the end of mechanical ventilation after surgery.
Other Name: Aibeining (trade name)
Placebo Comparator: Placebo group
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.
Drug: 0.9% sodium chloride for injection
Before anesthesia, 0.9% sodium chloride for injection 50 ml will be prepared.
Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes, followed by continuous infusion at a rate of [0.1*kg] ml/h until the end of surgery.
At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h and continued until the end of mechanical ventilation after surgery.
Other Name: normal saline
- Incidence of Postoperative Delirium [ Time Frame: During the first five days after surgery ]Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) twice daily during the first five days after surgery.
- Cognitive Function [ Time Frame: on the sixth day after surgery, and on the 30th day after surgery ]
Cognitive function was assessed with the Mini Mental State Examination (MMSE) at baseline (the day before surgery) and on the sixth day after surgery, and with modified telephone interview for cognitive status (m-TICS) on the 30th day after surgery.
The introduction of MMSE scale has been explained in the baseline part in the result section.
The Telephone Interview for Cognitive Status-modified scale(m-TICS) is one of the most popular telephone interview-based screening instruments for mild cognitive impairment and dementia. It consists 11 items including wordlist memory, orientation, attention, repetition, conceptual knowledge and nonverbal praxis, which score ranges from 0 to 48, with higher scores indicating better cognitive function
- Incidence of Non-delirium Complications After Surgery [ Time Frame: Occurrence of non-delirium complications will be monitored until 30 days after surgery. ]Non-delirium complications was defined as any conditions other than delirium that occurred during the first 30 days after surgery and required therapeutic intervention.Complications listed here were not considered adverse events in this study.
- Pain Intensity [ Time Frame: During the first five days after surgery ]Pain intensity was assessed daily at 8 am during the first five days after surgery with the Numeric Rating Scale (NRS, 0 = no pain, 10 = the worst possible pain).
- Subjective Sleep Quality [ Time Frame: During the first five days after surgery ]Subjective sleep quality was assessed daily at 8 am during the first five days after surgery with the Numeric Rating Scale (NRS, 0 = best sleep, 10 = the worst possible sleep).
- Length of Stay in the Intensive Care Unit [ Time Frame: From end of surgery until discharge from Intensive Care Unit or 30 days after surgery ]Results was presented as median (95% confidence interval).
- Length of Stay in Hospital After Surgery [ Time Frame: From end of surgery until discharge from hospital or 30 days after surgery ]Results was presented as median (95% confidence interval).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02267538
|Peking University First Hospital|
|Beijing, Beijing, China, 100034|
|Principal Investigator:||Dong-Xin Wang, MD, PhD||Peking University First Hospital|