Ketomidate versus Ketofol for Induction of Anesthesia in Patients with Aneurysmal Subarachnoid Hemorrhage Undergoing Clipping Surgery: A Prospective Randomized Double-blind Trial.

Aneurysmal subarachnoid hemorrhage (SAH) is a neurosurgical emergency. Surgical clipping and endovascular coiling are the preferred treatment options. The anesthetic goals include smooth induction and emergence, with blood pressure control, control of intracranial pressure (ICP), intraoperative brain swelling, and maintenance of adequate cerebral perfusion pressure (CPP).Propofol is an induction agent, it decreases cerebral blood flow (CBF) and maintains flow-metabolism coupling. However, systemic vasodilatory effects of propofol can cause a decrease in blood pressure. In contrast, ketamine, a phencyclidine derivative, increases cerebral metabolic rate and CBF and has strong sympathomimetic activity. For these reasons, it has been infrequently used during neurosurgical cases. However, sympathomimetic actions of ketamine increase mean arterial pressure (MAP) and possibly increase CPP which can prevent secondary brain injury. Etomidate is an anesthetic agent that has minimal effect on circulation. It can effectively maintain hemodynamics and effect on heart rate and blood pressure is much lower than that of other anesthetic drugs, which can reduce the probability of arrhythmias and other phenomena in patients. Alongside it can reduce the incidence of postoperative cognitive dysfunction and can also shorten postoperative hospital stays. The addition of ketamine to etomidate could have a synergistic effect on the neurocognitive outcome of patients with stable hemodynamics intraoperatively.

Optic nerve sheath diameter (ONSD) is a simple, safe, inexpensive, and bedside diagnostic tool to monitor intracranial pressure non-invasively. An increase in ICP causes enlargement of the ONSD, which can be measured indirectly using an ultrasound.

Through this trial, we would like to compare ketomidate with ketofol among patients with cerebral aneurysms undergoing clipping surgery. To the best of our knowledge and literature search, no randomized controlled trial has compared the effect between the above-mentioned drugs. We hypothesized that ketomidate would be non-inferior to ketofol in decreasing ICP and maintaining stable hemodynamics without compromising brain relaxation.. We hypothesized that Ketomidate would be non-inferior to ketofol in decreasing ICP and maintaining stable hemodynamics without compromising brain relaxation.We hypothesized that Ketomidate would be non-inferior to ketofol in decreasing ICP and maintaining stable hemodynamics without compromising brain relaxation.After clearance from the institutional ethical committee (IEC), registering in CTRI, and obtaining written informed consent, 46 patients will be randomized into two study groups based on a computer-generated random number. The group allocation will be concealed by keeping the numbers in sealed opaque envelopes that will be opened just before shifting the patient to the operation room (OR).Patients will be shifted into the OR and standard American Society of Anesthesiologists (ASA) monitoring like electrocardiogram (ECG), non-invasive blood pressure (NIBP), pulse oximetry (SPO2) and temperature will be initiated. An intravenous (IV) line will be secured and 0.9% normal saline will be started. General anesthesia induction will be done with an IV injection of fentanyl 2mcg/ kg and injection of lignocaine 1.5 mg/kg followed by the study drug in titration till loss of verbal response as per group allocation.

Group KM: IV injection Ketomidate (1:5 of Ketamine: Etomidate) will be used for induction in titration.

Group KF: IV injection of Ketofol (1:5 of Ketamine: Propofol) will be used for induction in titration.

After establishing bag and mask ventilation, an IV injection of rocuronium 1 mg/kg will be used for muscle relaxation under the guidance of neuromuscular transmission (NMT) monitoring. Preoxygenation will be carried out for four minutes. Following this, the airway will be secured with an appropriately sized endotracheal tube (ETT). Proper placement of the ETT will be confirmed by capnography, bilateral symmetrical chest rise, and air entry on chest auscultation. Patients in both groups will be ventilated using volume control mode and tidal volume (VT) and respiratory rate (RR) will be adjusted to maintain end-tidal carbon dioxide between 30-35 mm Hg. Maintenance of anesthesia will be done with 50:50% oxygen: air with total intravenous anesthesia (TIVA) using intravenous infusion of propofol (50-150 mcg/kg/min), intermittent atracurium [as per train of four (TOF) count] and fentanyl as per patient requirement. Other anesthetic management will be carried out as per our institutional protocol. In both groups, ONSDs will be measured in both eyes using an ultrasonography device in the supine position. A Tegaderm will be used to cover the closed eye so that the water-soluble gel doesn’t enter the eye. A 7.5 MHz linear ultrasound probe will be gently placed in the transverse plane over the gel. The ONSD will be measured 3 mm behind the optic disc using an electronic caliper. The ONSD measurement values will be determined for each eye by calculating the mean value of the 3 measurements. It will be measured before induction (T0), immediately after establishing the bag and mask ventilation (T1), after intubation (T2), after 5 minutes (T3), and after 10 minutes (T4). The patient will be handed over to the surgeon to carry out surgery. A subdural intracranial pressure will be measured on a dural opening using a 20G intravenous cannula transduced to the invasive pressure measurement transducer. The intraoperative brain relaxation score will be assessed by the operating surgeon based on a four-scale grading.