Morphine with adjuvant ketamine vs higher dose of morphine alone for immediate postthoracotomy analgesia

Thoracotomy is associated with severe pain. We hypothesized that the concomitant use of a subanesthetic dose of ketamine plus a two-third-standard morphine dose might provide more effective analgesia with fewer side effects than a standard morphine dose for early pain control.

We conducted a 6-month randomized, double-blind study in patients undergoing thoracotomy for minimally invasive direct coronary artery bypass or for lung tumor resection. After extubation, when objectively awake (>or= 5/10 visual analogue scale [VAS]) and complaining of pain (>or= 5/10 VAS), patients were connected to patient-controlled IV analgesia delivering 1.5 mg of morphine plus saline solution (MO) or 1.0 mg of morphine plus a 5-mg ketamine bolus (MK), with a 7-min lockout time. Rescue IM diclofenac, 75 mg, was available. Follow-up lasted 4 h.

Forty-one patients completed the study. MO patients (n = 20) used 6.8 +/- 1.9 mg/h (mean +/- SD) and 5.5 +/- 3.6 mg/h of morphine during the first and second hours, respectively; MK patients (n = 21) used 3.7 +/- 1.2 mg/h and 2.8 +/- 2.3 mg/h, respectively (p < 0.01). The 4-h activation rate of the device was double in the MO patients than in the MK patients (66 +/- 54 vs 28 +/- 20, p < 0.001). The maximal self-rated pain score was 5.6 +/- 1.0 for the MO group vs 3.7 +/- 0.7 for the MK group (p < 0.01). Four MO patients vs one MK patient required diclofenac; 6 MO patients but no MK patients had oxygen saturation by pulse oximetry < 94% on a fraction of inspired oxygen of 0.4 (p < 0.01); two MO patients required reintubation. Paco(2) was higher in the MO group (40 +/- 6 mm Hg vs 33 +/- 5 mm Hg, p < 0.05). Heart rate, BP, and incidence of nausea/vomiting were similar; no ketamine-related hallucinations were detected.

Subanesthetic ketamine combined with a 35%-lower morphine dose provided equivalent pain control compared to the standard morphine dose alone, with fewer adverse side effects and a 45% reduction in morphine consumption.

ClinicalTrials.gov Identifier: NCT00625911.