Plasticity of Central Chemoreceptors: Effect of Bilateral Carotid Body Resection on Central CO2 Sensitivity

Bilateral carotid body resection in three individuals led to reduced sensitivity of central chemoreceptors to CO2, followed by a gradual return, providing evidence of central plasticity within the ventilatory control system

Effect of variations in depth of neuromuscular blockade on rating of surgical conditions by surgeon and anesthesiologist in patients undergoing laparoscopic renal or prostatic surgery (BLISS trial): study protocol for a randomized controlled trial

Perioperative Medicine: Efficacy, Safety and Outcom

Pharmacodynamic analysis of the analgesic effect of capsaicin 8% patch (Qutenza™) in diabetic neuropathic pain patients: detection of distinct response groups

Treatment of chronic pain is associated with high variability in the response to pharmacological interventions. A mathematical pharmacodynamic model was developed to quantify the magnitude and onset/offset times of effect of a single capsaicin 8% patch application in the treatment of painful diabetic peripheral neuropathy in 91 patients. In addition, a mixture model was applied to objectively match patterns in pain-associated behavior. The model identified four distinct subgroups that responded differently to treatment: 3.3% of patients (subgroup 1) showed worsening of pain; 31% (subgroup 2) showed no change; 32% (subgroup 3) showed a quick reduction in pain that reached a nadir in week 3, followed by a slow return towards baseline (16% ± 6% pain reduction in week 12); 34% (subgroup 4) showed a quick reduction in pain that persisted (70% ± 5% reduction in week 12). The estimate of the response-onset rate constant, obtained for subgroups 1, 3, and 4, was 0.76 ± 0.12 week−1 (median ± SE), indicating that every 0.91 weeks the pain score reduces or increases by 50% relative to the score of the previous week (= t½). The response-offset rate constant could be determined for subgroup 3 only and was 0.09 ± 0.04 week−1 (t½ 7.8 weeks). The analysis allowed separation of a heterogeneous neuropathic pain population into four homogenous subgroups with distinct behaviors in response to treatment with capsaicin. It is argued that this model-based approach may have added value in analyzing longitudinal chronic pain data and allows optimization of treatment algorithms for patients suffering from chronic pain conditions

Tapentadol treatment results in long-term pain relief in patients with chronic low back pain and associates with reduced segmental sensitization

Introduction:Chronic low back pain (CLBP) is one of the most common chronic pain conditions in pain practice.Objectives:In the current study, we describe phenotypes of patients with CLBP based on the status of their endogenous pain modulatory system.Methods:Conditioned pain modulation (a measure of central pain inhibition), temporal summation (TS, a measure of pain facilitation), and offset analgesia (a measure of temporal filtering of nociception) were evaluated in 53 patients with CLBP at painful and nonpainful sites. Next, in a double-blind, randomized, placebo-controlled trial, 40 patients with defective conditioned pain modulation responses received treatment with tapentadol prolonged-release or placebo for 3 months.Results:The majority of patients (87%) demonstrated loss of central pain inhibition combined with segmentally increased TS and reduced offset analgesia at the lower back region. During treatment, tapentadol reduced pain intensity more than placebo (tapentadol -19.5 2.1 mm versus placebo -7.1 +/- 1.8 mm, P = 0.025). Furthermore, tapentadol significantly decreased pain facilitation by reduction of TS responses at the lower back (tapentadol -0.94 +/- 1.9 versus placebo 0.01 +/- 1.5, P = 0.020), which correlated with pain reduction (P < 0.001).Conclusion:Patients with CLBP demonstrated different phenotypes of endogenous pain modulation. In patients with reduced conditioned pain modulation, tapentadol produced long-term pain relief that coincided with reduction of signs of pain facilitation. These data indicate that the endogenous pain system may be used as a biomarker in the pharmacological treatment of CLBP, enabling an individualized, mechanism-based treatment approach.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

生後早期の新生児では、腹部外科手術後に低アルブミン血症による高アンバウンドビリルビン血症を引き起こす

博士（医学）神戸大

Sublingual sufentanil for postoperative pain relief: First clinical experiences

Background: The sublingual sufentanil tablet system (SSTS) is a novel hand-held patientcontrolled analgesia device developed for treatment of moderate-to-severe postoperative pain. Here we present the first results of its clinical use. Methods: Adult patients undergoing major surgery in five hospitals in the Netherlands received the SSTS for postoperative pain relief as part of multimodal pain management that further included paracetamol and a nonsteroidal anti-inflammatory drug (NSAID). The following variables were collected: postoperative pain scores using the 11-point numerical rating score (NRS) at rest, number of tablets used, occurrence of nausea, and patient satisfaction scores. Results: We included 280 patients in the study; the majority underwent laparoscopic abdominal (49%) or orthopedic (knee replacement) surgery (34%). The median NRS was 3.5 (interquartile range 2.3–4.0) on the day of surgery, 3.3 (2.3–4.0) on the first postoperative day, and 2.8 (2.0–4.0) on the second postoperative day; pain scores did not differ between surgery types. Mean number of tablets used was 19 (range 0–86). Nausea occurred in 34% of patients, more often in women (45% vs 19%). Overall satisfaction was high in 73% of patients. Satisfaction was correlated with pain relief (p < 0.001) and inversely correlated with occurrence of nausea (p=0.01). Discussion: In this data set obtained under real-life conditions we show that the SSTS effectively managed postoperative pain in abdominal and orthopedic surgeries. Future studies should determine patient populations that benefit most from the SSTS, assess the added values versus intravenous patient-controlled analgesia, and determine the pharmacoeconomics of the system