Dexmedetomidine Versus Morphine and Midazolam in Prevention and Treatment of Delirium After Adult Cardiac Surgery

Phase 4

Completed

Conditions: Delirium

Interventions: Drug: Dexmedetomidine Hydrochloride
Drug: Morphine and Midazolam

Registration Number: NCT03078946

Lead Sponsor: Ain Shams University

Brief Summary: This randomized double-blind parallel clinical study was conducted on 60 patients undergoing elective cardiac surgery under general anesthesia, at least 60 yr old, ASA I and II, 70-100 kg body weight and height 160-180 cm. Patients were randomized to: group A=30 patients receiving dexmedetomidine infusion (0.4- 0.7 µg /kg/h) or group B= 30 patients receiving morphine in a dose of 10-50μg/kg/hr as an analgesic with midazolam in a dose of 0.05mg/kg up to 0.2 mg/kg repeated as needed. Titration of the study medications infusions was conducted to maintain light sedation (RASS) (-2 to +1). Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care. If Delirium and agitation occurred: haloperidol 2.5-5 mg IV was given in repeated boluses. Secondary outcomes included ventilation time, additional sedation/analgesia, hemodynamics and adverse effects.

Detailed Description: Upon arrival at the ICU, a standardized protocol for postoperative care was implemented for all patients. Infusion rates for all sedative protocols were titrated in order to achieve and maintain light sedation (RASS -2 to +1) before extubation and (RASS 0) after extubation. All patients were extubated when deemed clinically appropriate according to local protocols. Because of their specific pharmacologic properties (i.e., respiratory depression), patients were weaned off propofol or midazolam infusions before extubation, whereas patients receiving dexmedetomidine were extubated while still on the medication and were kept on the maintenance infusion as deemed clinically necessary for a maximum of 24 hours.

Initial assessment and stabilization of both patient groups include; Clinical examination, hemodynamics (invasive blood pressure, heart rate, drains), activated clotting time, electrocardiography, chest x-ray and arterial blood gases including sodium and potassium. All patients were allowed to take 200 μg fentanyl and 5mg midazolam immediately on admission. Daily electrocardiography, chest x-ray, arterial blood gases including sodium and potassium, kidney function, coagulation profile if valve surgery or bleeding occurred, liver function if delirium occurred and CRP quantitative titre.

Delirium was monitored and reassessed up to a maximum of 7 days after surgery and the assessment takes place in two steps; Firstly, the level of consciousness must be assessed using the Richmond Agitation-Sedation Scale. If the patient appears to have a RASS score≥3, then evaluation of delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) can be performed. The CAM-ICU includes the assessment of 4 different features; acute change or fluctuating course of mental status, inattention, altered level of consciousness and disorganized thinking. CAM-ICU is considered positive when features 1 and 2 and either 3 or 4 are present (11). The CAM-ICU was performed once daily before midday, independent of additional analgesia or sedation. Abnormal or delirious behavior was recorded every shift by the bedside nurse (nurse:patient ratio 1:1) and reviewed by the research team. The number of delirium days was determined by following delirious patients until 7 days after surgery. Patients were considered delirium-free when they were free of delirium for more than 24 h and alive.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

elective cardiac surgery under general anesthesia
at least 60 yr old
ASA physical status I and II
70-100 kg body weight
height 160-180 cm.

Exclusion Criteria

Patients with impaired kidney or liver functions
history of cardiac or central nervous system disease
uncontrolled medical disease (diabetes mellitus and hypertension)
coagulation defect
history of drug or alcohol abuse
history of chronic pain or daily intake of analgesics
history of intake of non-steroidal anti-inflammatory drugs or opioids within 24 h before surgery
allergy to the used medications
or patient's refusal

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine Group (N=30)	Dexmedetomidine Hydrochloride	-
Morphine with Midazolam (N=30)	Morphine and Midazolam	-

Primary Outcome Measures

Name	Time	Method
The Incidence of Delirium (Number of Patients (in Digits))	Delirium was reported on day 7 post-surgery
The C-reactive Protein (CRP) Quantitative Titer Daily as Part of the Routine Clinical Care as a Prognostic Factor for Delirium (mg/L)	The maximum serum CRP level during the ICU stay was designated as max-CRP on day 7 post-surgery

Secondary Outcome Measures