Clinical trial NCT03078946: Dexmedetomidine Versus Morphine and Midazolam in Prevention and Treatment of Delirium After Adult Cardiac Surgery
Official title: Dexmedetomidine Versus Morphine and Midazolam in Prevention and Treatment of Delirium After Adult Cardiac Surgery; a Randomized, Double-blind Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Delirium
Keywords: Cardiac surgery
delirium
dexmedetomidine
morphine
midazolam
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2017-03-14
Enrollment: 60
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Incidence of Delirium (Number of Patients (in Digits))
timeFrame: Delirium was reported on day 7 post-surgery
measure: The C-reactive Protein (CRP) Quantitative Titer Daily as Part of the Routine Clinical Care as a Prognostic Factor for Delirium (mg/L)
timeFrame: The maximum serum CRP level during the ICU stay was designated as max-CRP on day 7 post-surgery
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Azeem TMA, Yosif NE, Alansary AM, Esmat IM, Mohamed AK. Dexmedetomidine vs morphine and midazolam in the prevention and treatment of delirium after adult cardiac surgery; a randomized, double-blinded clinical trial. Saudi J Anaesth. 2018 Apr-Jun;12(2):190-197. doi: 10.4103/sja.SJA_303_17.