The aim of this study is to illuminate the effect of combination of dexmedetomidine and oral melatonin versus the use of dexmedetomidine infusion alone on the improving of post-operative delirium (POD) on patients undergoing open brain surgeries.

Study Population: Patients undergoing open brain surgeries will be randomly assigned into one of the following groups using computer generated codes and opaque sealed envelopes:

1. Group A will receive Dexmedetomidine IV Infusion at rate of (0.5 μg/kg/hr) in addition to oral placebo tablets.

2. Group B will receive Dexmedetomidine IV Infusion at rate of (0.5 μg/kg/hr) in addition to oral Melatonin (3 mg/tablet).

   • Study Procedures:

A. Preoperative settings:

All patients will be assessed preoperatively by careful history taking, full physical examination, and laboratory evaluation.

B. Intraoperative settings:

As the patient is taken into the operating room, electrocardiography (ECG), non-invasive blood pressure (NIBP), pulse oximetry will be used, and IV line will be inserted.

Baseline parameters such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), and oxygen saturation (SpO2) will be recorded.

For all patients, anaesthesia will be induced using Propofol (2 mg/kg IV), Fentanyl (2 μg/kg IV), then patient will be intubated facilitated with Rocuronium (0.5 mg/kg IV) and the patient will be maintained on Isoflurane (1.2 - 1.5 MAC).

A central venous catheter would be inserted as well as an arterial line for invasive blood pressure monitoring.

End-tidal CO2 will be maintained between 25 and 30 mmHg. Fluids would be infused according to the patient's body weight with Ringer acetate through peripheral venous catheter and a fluid chart would be recorded.

Patients will receive Morphine (2.5-5 mg q3-4hr PRN, infused over 4-5 minutes). The study medications will be prepared by the local pharmacy in the form of Dexmedetomidine (4 μg/ml) in a 50 mL syringe. Melatonin tablets (3 mg/tablet) would be also provided as well as placebo tablets. Then will be handled to the anaesthesiologist in charge of the patient who will be blinded to the nature of the medications used and study medications would be started 15 minutes before the end of surgical procedure.

C. Postoperative settings:

After extubation, patients will be taken to the ICU. During the transfer to and on arrival vital data (Blood pressure, heart rate and saturation) will be measured and recorded.

The intensivist following up the patient will be blinded to the groups. Assessment of POD will be done after extubation and every 8 hours. The screening tool used to diagnose POD includes the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

D. Measurements

Primary outcome:

The incidence of POD after open brain surgeries. Secondary outcome

1. Time from extubation till discharge from ICU.
2. Incidence of postoperative nausea and vomiting (PONV).

Inclusion Criteria:

• Age: 30 - 60 years
• Sex: Both sexes
• Patients with open space occupying lesions or hematoma.

Exclusion Criteria:

• Refusal of the patient to give written informed consent.
• History of allergy to the medications used in the study.
• Psychiatric disorder.
• Any form of drug addiction.
• Patients receiving any anti-psychotic medications.
• History of previous brain insult (Ischemic or haemorrhagic infarctions).
• Pre-operative dementia.
• History of malignant hyperthermia
• Patient's suffering from bradycardia
• Patient's suffering from hypotension