Comparison of hemodynamics effects of Etomidate and Ketofol for endotracheal intubation in critically ill patients with liver disease: A randomized controlled trial.

**Importance of study:**Post intubation hypotension is a frequent occurrence in ICU. Due to vasodilation seen in patients with advanced liver disease this hypotension is even more profound in these patients. Various agents used to sedate the patient for intubation also impact the occurrence of hypotension as they affect the hemodynamics of the patients. Propofol, Etomidate and ketamine are commonly used sedative-hypnotic agents for this purpose. Ketofol which is an admixture of ketamine and propofol in equal ratios has also been used for this purpose.Etomidate acts by exerting its action of GABA receptors, but is known for its excellent hemodynamic tolerance due to simultaneous stimulation of α-2b adrenoreceptors. Ketamine is a NMDA receptor antagonist. It has sedative and analgesic properties and has a favorable hemodynamic profile as it causes release of endogenous catecholamines. Ketofol is an admixture of propofol and ketamine in equal ratio. This combination combines excellent intubating conditions provided by propofol with a superior hemodynamic profile provided by ketamine without any adrenal suppression. There is paucity of literature comparing the hemodynamics after using ketamine, ketofol and etomidate for sedation for intubation in critically ill liver disease patients. In this study we try to assess and compare the effects of etomidate and ketofol on post intubation hemodynamics in critically ill patients with advanced liver disease.

Study population.

All Adult Patients with advanced liver disease (MELDNa 15 or more) undergoing elective endotracheal intubation in ICU.

Study design: Prospective randomized controlled trial.

Allocation concealment: Patients will be randomized to either of two groups ie Group A receiving

etomidate and group B receiving ketofol using computer generated random number tables. Group

allocation will be sealed in an opaque envelope, which will be opened by ICU nurse not a part of the

study.

Blinding/Masking: Open label study

Methodology

Clearance from the institute ethics committee. Informed written consent will be obtained from the patients

after explaining the procedure. All patients will have oxygen saturation, pulse rate, ECG and arterial blood

pressure monitored. Patients will be randomized to either of two groups i.e. Group A receives etomidate

and group B receives ketofol using computer generated random number tables. Group allocation will be

sealed in an opaque envelope, which will be opened by an ICU nurse not a part of the study. Pre

oxygenation will be done with 100% oxygen using C-circuit and mask for three minutes. After

preoxygenation all patients will receive, depending on group allocation either 0.2-0.3 mg/kg etomidate or

1-2 mg/kg ketofol. This will be followed by 1.2 mg/kg injection of rocuronium. Gentle IPPV will be done

for 60 seconds. Under direct laryngoscopic guidance trachea will be intubated with appropriate size cuffed

endotracheal tube. After confirmation of bilateral equal air entry the tube will be fixed. Ventilator will be

connected with standard mode of ventilation.

Baseline heart rate, mean arterial pressure, oxygen saturation and vasopressor requirement will be noted

prior to induction.

These readings will be recorded post intubation as soon as the cuff is inflated and then every minute for next 5 minutes thereafter every five minutes till 30 minutes and then hourly till 6 hours.

Hypotension will be defined as MAP< 65 mmhg or more than 20% decrease in MAP from baseline (8).

Length of ICU stay, 7-day ,28 day mortality, ICU, ventilator , hospital and vasopressor free days till 28

days will also be noted and compared between the groups.

SOFA score will be noted prior to intubation and 24 hours post intubation. Any hypertension ( BP

140/90) within 5 minutes post intubation will be noted. Intubation difficulty score will be assessed.

Monitoring and assessment: Baseline heart rate, mean arterial pressure, oxygen saturation and

vasopressor requirement will be noted prior to induction. These readings will be recorded post intubation

as soon as the cuff is inflated and then every minute for next 5 minutes thereafter every five minutes till 30

minutes and then every hourly till 6 hours. Hypotension will be defined as MAP< 65 mmhg or more than

20% decrease in MAP from baseline. Length of ICU stay, 7-day ,28 day mortality, ICU, hospital and

vasopressor free days till 28 days and number of days on ventilator will also be noted and compared

between the groups. SOFA score will be noted prior to intubation and 24 hours post intubation.