Low Dose Dexmedetomidine and Delirium After Cardiac Surgery

Phase 4

Completed

• Conditions: Cardiac Surgical Procedures
• Interventions: Drug: Placebo; Drug: Dexmedetomidine

• Registration Number: NCT03388541
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

Delirium after cardiac surgery can occur in up to 50% of the patients and has been shown to be significantly associated with increased morbidity and mortality. Advanced age is a significant risk factor of delirium.

Numerous studies have shown that sedation with high doses of Dexmedetomidine in the ICU reduces the incidence of postoperative delirium. On the other hand animal studies have shown neuroprotective effects of Dexmedetomidine by means of stimulating alpha2A-adrenoceptors.

It is not clear whether the administration of a low dose Dexmedetomidine in cardiac surgery would have any neuroprotective effects by stimulating the alpha 2A-receptors and as such would decrease the incidence of postoperative delirium.

Detailed Description

Postoperative delirium (PD) is a common problem in cardiac surgical patients. Its incidence varies among studies and can reach up to 50% of the patients. PD is associated with increased morbidity and mortality. Its occurrence is the resultant between the predisposing factors and the precipitating factors. Age seems to be a significant predisposing factor. In this regard the pathophysiology of PD is not yet fully understood. There are several hypothetical mechanisms for the development of PD. The first hypothesis is cerebral ischemia and BBB breakdown. The second hypothesis is neuro-inflammation. Peripheral pro-inflammatory mediators especially released during surgery would interact with the brain. Otherwise there is the problem of sleep deprivation/fragmentation in patients admitted to the hospital.

Dexmedetomidine is a potent and more selective alpha2-adrenergic receptor than clonidine. Studies have demonstrated that it has neuroprotective and anti-inflammatory actions.

Numerous studies including trials in cardiac surgery have shown a decreased incidence of delirium when Dexmedetomidine was used as sedative in the ICU compared with other sedatives acting on the GABA receptors. However, in these studies high doses of Dexmedetomidine were used for periods up to 24h. Dexmedetomidine was started in the ICU and was not compared in a double-blind fashion with placebo. In a recent randomized double-blind placebo-controlled trial a very low dose of Dexmedetomidine decreased the occurrence of PD when compared to placebo. However this study was performed in non-cardiac patients. Moreover the patients were included after their arrival in the ICU, which means that those patients who were intubated at their arrival in the ICU were not included. And again the study medication was only started after arrival in the ICU.

The aim of this study is to elucidate whether the administration of Dexmedetomidine at a low dose would decrease the incidence of PD in elderly patients undergoing cardiac surgery. The hypothesis is that Dexmedetomidine at low doses, by only stimulating the alpha2A adrenoceptors,would have neuroprotective affects ans as such decrease the incidence of PD. Dexmedetomidine would also have anti-inflammatory effects and effects on the quality of sleep. Both mechanisms would play a role in the pathophysiology of PD.

Study Timeline

• Study First Submitted: 2017-08-01
• Study First Submitted QC: 2017-12-24
• Study First Posted: 2018-01-03
• Study Start: 2018-01-17
• Primary Completion: 2019-08-12
• Study Completion: 2019-08-12
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-28
• Last Update Posted: 2020-09-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

• Patients undergoing cardiac surgery with cardiopulmonary bypass

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Exclusion Criteria

• Hepatic dysfunction (hepatic function tests 3 times the normal value)
• Preoperative renal replacement therapy
• Preoperative delirium
• Emergency surgery not allowing neurologic evaluation by MMSE
• Mini invasive cardiac surgery
• Patients not speaking French

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	NaCl 0.9% will be administered at 5mL/h starting at the closure of the chest and continued during 10h.
Dexmedetomidine	Dexmedetomidine	Dexmedetomidine will be administered at 0.4ug/kg/h (5mL/h) starting at the closure of the chest and continued during 10h.

Primary Outcome Measures

Name	Time	Method
The incidence of delirium	Through study completion, an average of 30 days	The incidence of delirium detected by means of CAM-ICU and CAM

Secondary Outcome Measures

Name	Time	Method
Total dose of vasopressors	Through study completion, an average of 30 days	Total dose of vasopressors used in the ICU
Pace maker necessitation	Through study completion, an average of 30 days	Number of patients needing external pacing
Number of days spent in delirium	Through study completion, an average of 30 days	Total number of days in a delirious state
ICU stay	Through study completion, an average of 30 days	The duration of days admitted in the ICU and in the hospital
Total dose of analgesics	Through study completion, an average of 30 days	Total dose of analgesics used in the ICU
Hospital stay	Through study completion, an average of 30 days	The duration of days admitted in the hospital
Total dose sedatives	Through study completion, an average of 30 days	Total dose of sedatives used in the ICU
Total dose of inotropic agents	Through study completion, an average of 30 days	Total dose of inotropic agents used in the ICU

Trial Locations

Locations (1)

Cliniques Universitaires Saint Luc; 🇧🇪 Brussels, Belgium