Rakhman, E., Shmain, D., White, I., Ekstein, M.P., Kollender, Y., Chazan, S., . . . Weinbroum, A.A. (2011). Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: A randomized, placebo-controlled, double-blind trial. Clinical Therapeutics, 33(7), 863–873.

To determine whether the effect of ketamine on postoperative pain can be enhanced and prolonged if ketamine is administered IM in repeated and escalating subanesthetic doses before surgery; to determine if administration of ketamine as specified can reduce consumption of analgesia

Patients were randomized to receive a placebo (saline) or ketamine.

• The first 40 patients (consecutive) received one injection 3–4 hours before surgery. Group K1 received one ketamine injection.
• The next 40 patients received two injections, one injection 11–20 hours before surgery and another 3–4 hours before surgery. Group K2 received two ketamine injections.
• The last 40 patients received three injections, one injection 17–18 hours before surgery, one at 11–12 hours before surgery, and another 3–4 hours before surgery. Group K3 group received three ketamine injections.

Postoperatively, for two days, all patients received IV morphine, by means of patient-controlled analgesia (PCA), to control pain for as long as requested. PCA was initiated in the postanesthesia care unit. The PCA consisted of a bolus of 1.5 mg morphine. After a morphine dose, a patient could not access another dose for seven minutes.

• The sample was composed of 120 patients.
• Mean patient age was 43–47 years. Mean age varied by injection group.
• The sample included 69 males and 51 females.
• The sample included 42 cases of abdominal tumor, 25 cases of bowel tumor, and 53 cases of bone or muscle tumor.

• Single site
• Inpatient
• Israel
   

• Phase of care: end-of-life care
• Clinical applications: end-of-life and palliative care

Double-blind, placebo-controlled randomized controlled trial

• Numeric Rating Scale (NRS), a 0–10 scale of pain intensity, which patients completed every 15 minutes during the first postoperative hour and every 30 minutes until discharge from the PACU    
• Overall satisfaction, measured by means of a subjective response, before the patient's discharge, from the surgeon
• Adverse-event questionnaire
   

Group K2's mean 48-hour score (P = 0.0004) and group K3's mean 48-hour score (P = 0.046) were lower than the corresponding scores of the placebo groups. Compared to the placebo groups, patients in K2 and K3 used less morphine. PCA use was approximately 50% less than PSA use in placebo-group counterparts (P < 0.05). Ketamine at 25 mg caused dizziness for two minutes.

Two or three injections of ketamine before surgery for cancer attenuated postoperative pain and decreased opioid requirements for 48 hours after surgery.

• The study was conducted at one site only.
• The study assessed patients for 48 hours only.
• Patients were randomized for ketamine use but not for the number of doses received.
• Different types of surgery can be expected to yield different levels of postoperative pain.

Ketamine injections before cancer surgery may attenuate postoperative pain. Ketamine can be associated with dizziness and other side effects.