Ketamine in Colorectal Surgery

A prospective randomized, double blinded clinical trial of ketamine use in adult colorectal
surgery patients will be conducted. The experimental arm of the trial will receive ketamine
infusion therapy while the control arm of the trial receives saline placebo infusions at an
equivalent rate. All patients enrolled into the trial will be enrolled in a standardized
Enhanced Recovery after Surgery (ERAS) pathway which includes intravenous opioid medications
for breakthrough pain, scheduled acetaminophen, and NSAIDs as indicated. All patients will be
managed in accordance with the appropriate Division of Trauma and Acute Care Surgery and
Division of Colorectal Surgery policies.

Potential participants will be screened at the time of outpatient clinic visits. Patients who
require operative intervention for management of their colonic disease, both malignant and
non-malignant, are eligible for enrollment. Individuals who present to the emergency
department and are evaluated by the previously mentioned divisions will be screened for
eligibility. If a potential participant qualifies for enrollment, he or she will be
approached by one of the IRB approved study staff for consent. Prior to randomization and
formal enrollment, an investigational drug services pharmacist will screen for any
contraindication to potential ketamine therapy. Following investigator and pharmacy approval,
patients will be randomized by the Investigational Drug Services (IDS). The two trial arms
will be randomized in a 1:1 control to experimental fashion with randomization blocks
conducted in sets of 4 patients.

Participants who are enrolled into the trial will undergo randomization into either the
experimental or control arm by the IDS department at time of presentation to the hospital.
The infusate will be prepared by the IDS department at a ketamine concentration of
500mg/250ml with all IV bags labeled "Investigational Ketamine / Placebo - PRO27024" prior to
dispersal to the pre-operative nurse. All elective surgery patients will receive alvimopan
beginning in the pre-operative area and administered by the RN at least 30 minutes prior to
administration of narcotic medications. A total of 60 patients will be enrolled (see sample
size calculation in c.2.3), 30 into each arm. All infusion rates will be calculated based on
ideal body weight (IBW), unless actual body weight (ABW) is less than ideal. IBW is
calculated for males as 50kg + 2.3*(number of inches over 5 feet) and for females as 45.5kg +
2.3*(number of inches over 5 feet). All investigational infusions will be started by the
anesthesia resident or Certified Registered Nurse Anesthetists (CRNA) at the time of
anesthesia induction. Patients will receive a bolus of the investigational solution at a
calculated dose of 0.25 mg/kg over 5 minutes following anesthetic induction. A continuous
infusion of the investigational solution will immediately follow at a rate of 2 mcg/kg/min.
Timing of bolus administration along with time of initiation of continuous infusion will be
documented with the continuous infusion to run for a duration of 48-hours.

All subjects will be assessed daily or more frequently for delirium. The institutional CAM
and CAM-ICU Delirium screens, which have been validated in the literature, will be utilized
(see appendices IV and V). Subjects may remove oneself from the trial or be un-blinded should
he/she, pharmacy, and/or clinical staff deem it medically necessary. Medical necessity is
determined by inability to treat without knowledge of trial assignment; otherwise treating
staff will assume all patients have received ketamine. All adverse events will be recorded
and if necessary subjects will be un-blinded in the event of a serious adverse event.

All adverse events will be recorded and if necessary subjects will be un-blinded in the event
of a serious adverse event. The research team will monitor all study patients for any adverse
event trends. Patients will be followed through the time of discharge.

Inclusion Criteria:

1. Age greater than 18 years

2. Surgical intervention required for the management of colonic disease

3. Admission to either the acute care surgery or colorectal surgery service with an
anticipated inpatient hospital stay of 72 hours.

Exclusion Criteria:

1. History of adverse reaction to ketamine

2. Chronic opioid therapy for >3 weeks of >30mg oral morphine equivalents per day

3. Known substance abuse with prescription opioids or heroin

4. Anticipated post-operative intubation (>6hr duration)

5. History of psychosis

6. Active delirium

7. Glaucoma

8. Active acute coronary syndrome

9. Severe, poorly controlled hypertension (systolic blood pressure > 180)

10. Concurrent use of monoamine oxidase inhibitors (MAOIs)

11. Pregnancy

12. Prisoners