Two Ratios of Propofol-ketamine Admixture for Rapid-sequence Induction Anesthesia for Emergency Laparotomy

Hypotension during anesthesia is associated with serious organ failure and death. The most critical period for intraoperative hypotension is the postinduction period during which, one-third of intraoperative hypotension occurs. Post-induction hypotension has many contributing factors; however, it is closely related to anesthetic drugs. Therefore, manipulation of induction agents makes post-induction hypotension likely preventable. Emergency laparotomy is a critical category of surgery whose patients are usually hemodynamically compromised and prone to post-induction hypotension; furthermore, these patients are usually at high risk of aspiration of gastric contents and require rapid-sequence induction of anesthesia and optimum intubating conditions. Thus, induction of anesthesia for emergency laparotomy requires meticulous balance between achievement of adequate hypnosis and maintenance of stable blood pressure.

Propofol is the commonest hypnotic agent worldwide. However, it is usually associated with hypotension especially in compromised patients. Ketamine produces dissociative anesthesia and sympathetic stimulation which provides more stable hemodynamic profile; however, ketamine is not widely used as a routine hypnotic because it produces psychomimetic effects such as delirium and emergence agitation. Nevertheless, ketamine still has a role in induction of anesthesia in patients with shock and during procedural sedation. Ketamine is also used as analgesic adjuvant during general anesthesia.

Propofol/ketamine admixture (ketofol) was introduced in anesthetic practice aiming to compensate the side effects of the two drugs and to provide, consequently, the desired balance between adequate hypnosis and hemodynamic stability. Ketofol is currently used with a diversity in the ratio between the two drugs which ranges between 1:1 and 1:10 between ketamine and propofol. Despite its frequent use in sedation and complete anesthesia, most of the available literature for comparisons of different ketofol mixtures was restricted to procedural sedation whose results are not applicable in induction of anesthesia due to the different desirable level of hypnosis and recovery. Therefore, the best combination of the two components of ketofol for induction of anesthesia is unknown

Preoperatively, a trained anesthetist will assess the patients regarding the fasting hours, medical history, medications, laboratory investigation, as well as the patient's airway.

In the operating room, routine monitors (electrocardiogram, pulse oximetry, and non-invasive blood pressure monitor) will be applied; intravenous line will be secured, and routine pre-medications (dexamethasone 4 mg as 0.5 mg/ml slow I.V injection) will be administrated. Baseline preoperative blood pressure will be recorded in the supine position as average of 3 readings with difference less than 10% in the systolic blood pressure.

After 3-minutes preoxygenation, patients in the two groups will receive 1 mg/kg lidocaine (in a separate syringe) plus 0.15-0.2 mL/kg from the prepared mixture. This regimen will provide a dose of 1 mg/kg propofol + 1 mg/kg ketamine in the ketofol-1:1 group and 1.5 mg/kg propofol + 0.5 mg/kg ketamine in the ketofol-1:3 group.

Clinical loss of consciousness (defined as no response to auditory command and the disappearance of a patient's eyelash reflex). After loss of consciousness, succinylcholine 1 mg/kg will be administered over 5 seconds, and tracheal intubation will be done through direct laryngoscopy after 60 seconds.

The intubation conditions will be graded by the same anesthetist who performed intubation as excellent, good, or poor for :ease of laryngoscopy, Vocal cord position, Reaction to insertion of the tracheal tube and cuff inflation (Diaphragmatic movement/coughing) Excellent, all criteria excellent; good, all criteria either excellent or good; poor, presence of a single criterion graded as poor.

When the trachea is intubated, mechanical ventilation will be applied to obtain SpO2 \> 95% and end-tidal CO2 between 30-40 mmHg and anesthesia will be maintained by isoflurane. Atracurium will be administered after patient recovery from succinylcholine at a dose of 0.5 mg/Kg. Atracurium increments of 10 mg will be administered every 20 min for maintenance of muscle relaxation.

Any episode of hypotension (defined as mean arterial pressure \[MAP\] \<70 mmHg) will be managed by 5 mcg norepinephrine (which will be repeated if hypotension persists for 2 minutes).

If hypertension or tachycardia occurred (defined as MAP or heart rate \>120% of baseline), it will be managed by IV 0.5 mg/kg propofol.

After skin incision, hemodynamic and anesthetic management will be according to the attending anesthetist discretion.

Eligibility Criteria:
Inclusion Criteria:

* adult patients (18-65 years),
* American society of anesthesiologist I-III,
* scheduled for emergency laparotomy under general anesthesia

Exclusion Criteria:

* history of difficult intubation,
* abnormal airway examination,
* cardiac morbidities (impaired contractility with ejection fraction \< 50%, heart block, arrhythmias, tight valvular lesions),
* patients on angiotensin converting enzyme inhibitors and angiotensin receptor blockers medications,
* patients with uncontrolled hypertension,
* patient with allergy of any of the study drugs
* Patients on vasopressor infusion,
* patients with high shock index (heart rate / systolic blood pressure \>1),
* body mass index \> 35 kg/m2, increased intracranial tension
* pregnant women