The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial.

BACKGROUND: Evidence confirms that perioperative ketamine administration decreases opioid usage. To reduce the risk for potential psychodysleptic side effects, however, ketamine dosing tends to be limited to low-dose regimens. We hypothesized that even lower doses of ketamine would be sufficient, with minimal side effects, when used as a component of multimodal perioperative pain management. METHODS: In this triple-blinded, randomized, active- and placebo-controlled clinical trial, patients undergoing elective major abdominal surgery were randomized to one of three treatment groups: low-dose S-ketamine (a 0.25 mg/kg bolus and 0.125 mg/kg/h infusion for 48 hours), minimal-dose S-ketamine (a 0.015 mg/kg/h infusion following a saline bolus), and placebo (saline bolus and infusion). Opioid consumption, pain levels, hyperalgesia at the incision site, and delirium scores were assessed 48 h postoperatively. RESULTS: Patients in the placebo group had the highest cumulative piritramide consumption and the largest normalized areas of hyperalgesia at the incisional site, while those in the low-dose group had the highest delirium scores. Postoperative pain levels did not differ significantly between the treatment groups. CONCLUSIONS: Our data demonstrate that minimal-dose S-ketamine was comparable to the conventional low-dose regimen in reducing postoperative opioid consumption and hyperalgesia. Postoperative delirium, however, was less frequent with the minimal-dose regimen. We therefore suggest that minimal-dose S-ketamine may be a useful low-risk component of balanced perioperative analgesia.

Fentanyl for the treatment of tumor-related breakthrough pain.

BACKGROUND: Breakthrough cancer pain (BTCP) is common among cancer patients and markedly lowers their quality of life. The treatment for BTCP episodes that is recommended in current guidelines involves extended-release formulations in combination with rapid-onset and short-acting opioids. In the past few years, several new preparations of fentanyl, an opioid with a very rapid onset, have been approved for this indication. Treating physicians need to be aware of the clinical differences between the newer fentanyl preparations and immediate-release opioids. METHODS: We searched the PubMed and Embase databases for randomized controlled trials (RCTs) of fentanyl for buccal, sublingual or intranasal administration in comparison with other opioids or a different fentanyl preparation for the treatment of BTCP. RESULTS: In 6 trials of buccal, sublingual or intranasal fentanyl versus oral immediate-release opioids for the treatment of BTCP episodes, the use of fentanyl was associated with significantly less intense pain. In particular, fentanyl more often lowered the intensity of pain by at least 33% (range between studies: 13% to 57%) or by at least 50% (range between studies: 9% to 38%) within 15 minutes. Please change to "versus" if you agree.] Dose titration should begin at the lowest dose. When one fentanyl preparation is exchanged for another, the effective dose will probably differ. CONCLUSION: The newer fentanyl preparations extend the treatment options for BTCP. They relieve pain within a short time better than conventional, immediate-release oral opioids do and may therefore be very helpful for patients with suddenly arising, intense, and short-lasting BTCP episodes. Further comparative trials are urgently needed.