Local Anesthetics delivered through Pleural Drainages improve Pain and Lung Function after Cardiac Surgery.

OBJECTIVE: Pleural tubes after coronary artery bypass graft (CABG) surgery usually cause pain resulting interalia in an impact of postoperative breathing. Therefore, the influence of intrapleural lidocaine application through special double-lumen chest tubes with respect to pain relief and lung function was investigated and compared with placebo. METHODS: In this study, 40 patients who underwent CABG got intrapleural injection either with 2% lidocaine (n = 20) or placebo (0.9% saline solution) (n = 20) on the first 2 days after surgery. Pain was measured by pain intensity numeric rating scale (NRS) (0 = no pain; 10 = the most intense pain) and lung function by portable spirometer. RESULTS: On the first postoperative day (POD1), mean pain reduction was NRS 1.9 for the lidocaine group with an improvement of the forced expiratory volume in 1 second (FEV1) of 0.51 L. Similar results were shown on the second postoperative day (POD2) with a decreased pain level of mean NRS 1.65 and an FEV1 improvement of 0.26 L. In comparison, results of the placebo group showed no significant pain reduction, neither on the POD1 (NRS 0.35; p = 0.429) nor on the POD2 (NRS 0.55; p = 0.159). Also, there was no significant influence of FEV1 after placebo on the POD1 (FEV1 = 0.048 L; p = 0.70) or on the POD2 (FEV1 = 0.0135 L; p = 0.925). CONCLUSION: Intrapleural application of lidocaine is a safe and feasible method to reduce drainage-related pain and improving lung function after CABG.

Does Fentanyl Lead to Opioid-induced Hyperalgesia in Healthy Volunteers?: A Double-blind, Randomized, Crossover Trial.

BACKGROUND: Although opioids in general and remifentanil in particular have been shown to induce hyperalgesia, data regarding fentanyl are scarce. Thus, the authors investigated the effect of fentanyl dosing on pain perception and central sensitization in healthy volunteers using established pain models. METHODS: Twenty-one healthy, male volunteers were included in this randomized, double-blind, crossover study and received either intravenous low-dose (1 µg/kg) or high-dose (10 µg/kg) fentanyl. Pain intensities and hyperalgesia were assessed by intracutaneous electrical stimulation, and cold pressor pain was used as an additional measure of acute pain. The primary outcome was hyperalgesia from 4.5 to 6.5 h after fentanyl administration. RESULTS: A higher dose of fentanyl led to significantly decreased pain scores as measured by the numeric rating scale (0.83 units lower [95% CI, 0.63 to 1.02]; P < 0.001) but increased areas of hyperalgesia (+30.5% [95% CI, 16.6 to 44.4%]; P < 0.001) from 4.5 to 6.5 h after fentanyl administration. Allodynia did not differ between groups (+4.0% [95% CI, -15.4 to 23.5%]; P = 0.682).The high dose also led to both increased cold pressor pain threshold (+43.0% [95% CI, 29.7 to 56.3%]; P < 0.001) and tolerance (+32.5% [95% CI, 21.7 to 43.4%]; P < 0.001) at 4.5 to 6.5h. In the high-dose group, 19 volunteers (90%) required reminders to breathe, 8 (38%) required supplemental oxygen, and 12 (57%) experienced nausea. CONCLUSIONS: A higher dose of fentanyl increased hyperalgesia from 4.5 to 6.5 h in healthy volunteers while simultaneously decreasing pain scores.

Analgesic and antihyperalgesic properties of propofol in a human pain model.

BACKGROUND: Propofol (Disoprivan, AstraZeneca AG, Zug, Switzerland) has long been considered to be nonanalgesic. However, accumulating evidence shows that propofol possesses modulatory action on pain processing and perception. In this study, the authors investigated the modulatory effects of propofol and a formulation similar to the solvent of propofol (10% Intralipid; Fresenius Kabi, Stans, Switzerland) on pain perception and central sensitization in healthy volunteers. METHODS: Fourteen healthy volunteers were included in this randomized, double-blind, placebo-controlled, crossover study. Intracutaneous electrical stimulation (48.8 +/- 25.8 mA) induced spontaneous acute pain (Numeric Rating Scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia were assessed regularly before, during, and after a 45-min target-controlled infusion (2 microg/ml) of propofol, the solvent 10% Intralipid, and saline. RESULTS: During administration, propofol significantly decreased pain scores and areas of hyperalgesia and allodynia compared with both 10% Intralipid and saline (placebo-corrected mean Numerical Rating Scale score reduction by propofol: 38 +/- 28%). This difference disappeared shortly after cessation of the infusion. Thereafter, no significant group differences were observed in the Numerical Rating Scale score and the areas of hyperalgesia or allodynia. However, there was a trend to reduced hyperalgesia and allodynia after propofol treatment. Pharmacodynamic modeling regarding the analgesic effect of propofol showed an EC50 (half-maximum effect site concentration) of 3.19 +/- 0.37 microg/ml. Ten percent Intralipid was free of pain-modulatory effects in the authors' experiments. CONCLUSIONS: Propofol showed short-lasting analgesic properties during its administration, whereas the solvent-like formulation 10% Intralipid had no effect on pain perception.

Current knowledge of buprenorphine and its unique pharmacological profile.

Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other µ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full µ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain.

Tropisetron blocks analgesic action of acetaminophen: a human pain model study.

Because the mechanism underlying the analgesic action of acetaminophen remains unclear, we investigated the possible interaction of acetaminophen with central serotonergic pathways. The effects of acetaminophen, tropisetron, the combination of both drugs, and saline on pain perception and central sensitization in healthy volunteers were compared. Sixteen healthy volunteers were included in this randomized, double-blind, placebo-controlled crossover study. Intracutaneous electrical stimulation (46.1 ± 19.1 mA) induced acute pain (numeric rating scale, 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia and allodynia were regularly assessed before, during, and after a 15-min infusion of acetaminophen, tropisetron, the combination of both drugs, and saline. Acetaminophen concentrations were measured to rule out any pharmacokinetic interaction. Both acetaminophen and tropisetron led to decreased pain ratings as compared to saline. However, when acetaminophen and tropisetron were administered simultaneously, the pain ratings were not affected. There was no significant difference in the evolution of the hyperalgesic and allodynic areas during the study period between the study groups (P = .06 and P = .33, respectively). Acetaminophen serum levels were not significantly different when associated with tropisetron (P = .063), although we observed a trend toward lower acetaminophen concentrations when both drugs were concurrently administered. In summary, while the combination of acetaminophen and tropisetron showed no analgesic action, each drug administered alone led to decreased pain ratings as compared to saline. In an electrically evoked human pain model, the combination of acetaminophen with tropisetron was free of any analgesic potential. However, when administered on its own, both acetaminophen and tropisetron were mildly analgesic.