Single-dose dexamethasone as an analgesic

AORN Journal, July, 2008 by George Allen

Anesthesia & Analgesia

April 2008

Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. It is extensively used in the perioperative setting, and a single preoperative dose of this medication has gained widespread acceptance as an effective preventive treatment for postoperative nausea. Recently, single doses of larger amounts of dexamethasone and other glucocorticoids have been reported to improve analgesia after various surgical procedures, including lower limb orthopedic procedures; laparoscopic cholecystectomy; and foot, breast, and spine surgeries.

Total hip arthroplasty (THA) is an increasingly common procedure that results in significant postoperative pain that generally is controlled with IV patient-controlled analgesia (PCA) using morphine and regular doses of acetaminophen and ibuprofen. Patients using PCA often experience nausea and other opioid side effects. The level of C-reactive protein (CRP), an acute phase plasma protein that serves as a marker for inflammation, has been found to peak at 48 hours after THA and correlate with pain and functional outcomes in the postoperative period until hospital discharge. It has been suggested that this postoperative inflammatory response may be more effectively inhibited by systemic glucocorticoids than by regional anesthesia. The hypothesis of this randomized, double-blind, placebo-controlled study was that because of its prolonged anti-inflammatory effect, a single preoperative IV dose of dexamethasone 40 mg would reduce dynamic pain 24 hours after THA.

Fifty patients undergoing elective, unilateral, primary THA under spinal anesthesia at a university hospital in Canada were randomly assigned to receive either IV dexamethasone 40 mg or a saline placebo (ie, 25 patients in each group). Patients were excluded from the study if they

* were younger than 18 years of age;

* were unable to communicate lucidly in English or French;

* were undergoing revision hip replacement;

* had a contraindication to spinal anesthesia;

* had renal failure;

* had peptic ulcer disease;

* had been treated with steroids or immunosuppressive medications in the past six months;

* had diabetes mellitus type I or II; or

* were hypersensitive to morphine, bupivicaine, nonsteroidal anti-inflammatory drugs, or the study medication.

Preoperatively, a normal saline infusion was started and an IV propofol infusion was administered for sedation at the discretion of the anesthesiologist; the total dose administered throughout the procedure was recorded. After the induction of spinal anesthesia, the study medication or placebo was administered by IV over 10 minutes. The total surgical time, defined as the interval between the skin incision and arrival in the postanesthesia care unit (PACU), was recorded. Postoperatively, patients were assessed for pain using an 11-point numeric rating scale (NRS) with zero equaling no pain and 10 equaling the worst pain imaginable. Patients received morphine 1 mg to 2 mg IV every five minutes to achieve a pain rating of less than 4. Subsequently, morphine i mg IV was administered every seven minutes as needed for 48 hours.

All patients received acetaminophen 650 mg and ibuprofen 400 mg, with the first dose administered when PCA with morphine was started. The time to the first PCA dose was measured from arrival in the PACU. Hip pain was measured both at rest and as dynamic (ie, standing up) using the NRS. The anesthesiologist recorded baseline preoperative values for each patient, and the PACU nurses recorded pain scores at rest every four hours for 48 hours postoperatively. Dynamic pain scores were recorded at 24 hours before physiotherapy began, and the PACU and ward nurses assessed side effects every four hours during the 48-hour study period.

Nausea and vomiting were defined as episodes requiring treatment, and CRP levels were measured at 48 hours on the last 25 patients randomly assigned to the study. In addition, one month after surgery, each patient's inpatient and outpatient follow-up hospital record was reviewed for any documentation of wound complications or infection. Common statistical techniques including the Pearson chi-square test, Fisher exact test, and analysis of variance were used to analyze the data.

FINDINGS. There was no significant difference between the two groups in demographic variables. Surgical time was shorter and intraoperative propofol use was greater in the dexamethasone group. There was no significant difference in pain at rest at any time period; however, dynamic pain NRS scores at 24 hours were significantly lower in the dexamethasone group compared to the placebo group (2.6, 95% confidence interval [CI] 2.2-3.0 versus 6.9, 95% CI 6.5-7.3, respectively; P < .000). After adjustment for surgical time and intraoperative propofol use, the significant difference remained (2.7, 95% CI 2.2-3.1 versus 6.8, 95% CI 6.4-7.2; P < .000). C-reactive protein levels at 48 hours were significantly reduced by dexamethasone (52.4 mg/mL, 28.2-76.6 versus 194.2 mg/mL, 168.9-219.4; P < .000). Seven patients in the placebo group were treated for nausea compared to one patient in the dexamethasone group (P = .05).