26 de novembro de 2013

Artigo recomendado: Lidocaine Patch (5%) in Treatment of Persistent Inguinal Postherniorrhaphy Pain"

A Randomized, Double-blind, Placebo-controlled, Crossover Trial

Joakim M. Bischoff, Marian Petersen, Nurcan Üçeyler, Claudia Sommer, Henrik Kehlet, Mads U. Werner


Background: Evidence-based pharmacological treatment options for patients with persistent inguinal postherniorrhaphy pain are lacking.

Methods: Twenty-one male patients, with severe, unilateral, persistent inguinal postherniorrhaphy pain, participated in a randomized, double-blind, placebo-controlled crossover trial, receiving lidocaine patch (5%) and placebo patch treatments in periods of 14 days separated by a 14-day wash-out period. Pain intensities (at rest, during movement, and pressure evoked [Numerical Rating Scale]) were assessed before treatment and on the last 3 days of each treatment period. Patients were a priori divided into two subgroups based on quantitative sensory testing (+/− thermal “hyposensitivity”). Skin biopsies for intraepidermal nerve fiber density assessment were taken at baseline, and quantitative sensory testing was performed before and after each treatment period. The primary outcome was change in pain intensity assessed as the difference in summed pain intensity differences between lidocaine and placebo patch treatments.

Results: There was no difference in summed pain intensity differences between lidocaine and placebo patch treatments in all patients (mean difference 6.2% [95% CI = −6.6 to 18.9%]; P = 0.33) or in the two subgroups (+/− thermal “hyposensitivity”). The quantitative sensory testing (n = 21) demonstrated an increased pressure pain thresholds after lidocaine compared with placebo patch treatment. Baseline intraepidermal nerve fiber density (n = 21) was lower on the pain side compared with the nonpain side (−3.8 fibers per millimeter [95% CI = −6.1 to −1.4]; P = 0.003). One patient developed mild erythema in the groin during both treatments.

Conclusions: Lidocaine patch treatment did not reduce combined resting and dynamic pain ratings compared with placebo in patients with severe, persistent inguinal postherniorrhaphy pain.

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14 de novembro de 2013

Artigo recomendado: Nocturnal Intermittent Hypoxia Is Independently Associated with Pain in Subjects Suffering from Sleep-disordered Breathing

Anthony G . Doufas, L u Tian, Margaret Frances Davies, Simon C. Warby

Anesthesiology 2013; 119:1149-62

Background: On the basis of experimental and clinical evidence, the authors hypothesized that nocturnal hypoxemia would be associated with pain reports in subjects suffering from sleep-disordered breathing, independently of sleep fragmentation and inflammation.

Methods: After obtaining institutional approval and access to the Cleveland Family Study phenotype and genotype data, the authors used proportional odds regression to examine the association between arterial desaturation and four different types of pain, as well as their composite measure, sequentially adjusted for: (1) clinical characteristics and (2) sleep fragmentation and inflammation. The authors also examined the association of selected candidate single-nucleotide polymorphisms with pain reports.

Results: Decreased minimum nocturnal arterial saturation increased the odds for morning headache (adjusted odds ratio per SD = 1.36; 95% CI [1.08–1.71]; P = 0.009), headache disrupting sleep (1.29 [1.10–1.51]; P = 0.002), and chest pain while in bed (1.37 [1.10–1.70]; P = 0.004). A decrease in the minimum nocturnal saturation from 92 to 75% approximately doubled the odds for pain. One singlenucleotide polymorphism for the a 1 chain of collagen type XI (COL11A1–rs1676486) gene was significantly associated with headache disrupting sleep (odds ratio = 1.72 [1.01–2.94]; P = 0.038), pain disrupting sleep (odds ratio = 1.85 [1.04–3.28]; P = 0.018), and pain composite (odds ratio = 1.89 [1.14–3.14]; P = 0.001).

Conclusion: Nocturnal arterial desaturation may be associated with an increased pain in subjects with sleep-disordered breathing, independently of sleep fragmentation and inflammation.

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12 de novembro de 2013

Artigo recomendado: Epigenetic Regulation of Spinal CXCR2 Signaling in Incisional Hypersensitivity in Mice

Yuan Sun, Peyman Sahbaie, De-Yong Liang, Wen-Wu Li, Xiang-Qi Li, Xiao-You Shi, J. David Clark

Anesthesiology 2013; 119:1198-208

Background: The regulation of gene expression in nociceptive pathways contributes to the induction and maintenance of pain sensitization. Histone acetylation is a key epigenetic mechanism controlling chromatin structure and gene expression. Chemokine CC motif receptor 2 (CXCR2) is a proinflammatory receptor implicated in neuropathic and inflammatory pain and is known to be regulated by histone acetylation in some settings. The authors sought to investigate the role of histone acetylation on spinal CXCR2 signaling after incision.

Methods: Groups of 5–8 mice underwent hind paw incision. Suberoylanilide hydroxamic acid and anacardic acid were used to inhibit histone deacetylase and histone acetyltransferase, respectively. Behavioral measures of thermal and mechanical sensitization as well as hyperalgesic priming were used. Both message RNA quantification and chromatin immunoprecipitation analysis were used to study the regulation of CXCR2 and ligand expression. Finally, the selective CXCR2 antagonist SB225002 was administered intrathecally to reveal the function of spinal CXCR2 receptors after hind paw incision.

Results: Suberoylanilide hydroxamic acid significantly exacerbated mechanical sensitization after incision. Conversely, anacardic acid reduced incisional sensitization and also attenuated incision-induced hyperalgesic priming. Overall, acetylated histone H3 at lysine 9 was increased in spinal cord tissues after incision, and enhanced association of acetylated histone H3 at lysine 9 with the promoter regions of CXCR2 and keratinocyte-derived chemokine (CXCL1) was observed as well. Blocking CXCR2 reversed mechanical hypersensitivity after hind paw incision.

Conclusions: Histone modification is an important epigenetic mechanism regulating incision-induced nociceptive sensitization. The spinal CXCR2 signaling pathway is one epigenetically regulated pathway controlling early and latent sensitization after incision.

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8 de novembro de 2013

Artigo recomendado: Positive End-expiratory Pressure Influences Echocardiographic Measures of Diastolic Function

A Randomized, Crossover Study in Cardiac Surgery Patients

Peter Juhl-Olsen, Johan Fridolf Hermansen, Christian Alcaraz Frederiksen, Linda Aagaard Rasmussen, Carl-Johan Jakobsen, Erik Sloth

Background: Ultrasonography of the cardiovascular system is pivotal for hemodynamic assessment. Diastolic function is evaluated with a combination of tissue Doppler (e’ and a’) and pulsed Doppler (E and A) measures of transmitral- and mitral valve annuli velocities. However, accurate echocardiographic evaluation in the intensive care unit or perioperative setting is contingent on relative resistance to positive pressure ventilation and changes in preload. This study aimed to evaluate the effects of positive end-expiratory pressure (PEEP) and positioning on echocardiographic measures of diastolic function.

Methods: The study was a prospective, randomized, crossover study. Cardiac surgery patients with ejection fraction greater than 45% and averaged e’ of 9 or more were included. Postoperatively, anesthetized patients were randomized into six combinations of PEEP (0, 6, 12 cm H2O) and positions (horizontal, Trendelenburg). At each combination, e’ (primary endpoint), a’, E, and A were obtained with transesophageal echocardiography along with left ventricular area. Image analysis was performed blinded to the protocol.

Results: Thirty patients completed the study. PEEP decreased lateral e’ from 6.6 ± 3.6 to 5.3 ± 3.0 cm/s (P < 0.001) in the horizontal position and from 7.4 ± 4.2 to 6.5 ± 3.3 cm/s (P < 0.001) in Trendelenburg. Similar results were found for septal e’, a’ bilaterally and transmitral pulsed Doppler measures, and PEEP decreased left ventricular area. E/A, E/e’, and e’/a’ remained unaffected by PEEP and positioning.

Conclusions: When evaluating diastolic function by echocardiography, the levels of PEEP and its effect on ventricular area have to be taken into account. In addition, this study dissuades the use of E/e’ for tracking changes in left ventricular filling pressures in cardiac surgery patients.

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5 de novembro de 2013

Artigo recomendado: Perioperative Gabapentinoids

Choice of Agent, Dose, Timing, and Effects on Chronic Postsurgical Pain

Peter C. Schmidt, Gabriela Ruchelli, Sean C. Mackey, Ian R. Carroll

The gabapentinoids pregabalin and gabapentin are both indicated for the treatment of postherpetic neuralgia and as adjuvant therapy for seizure disorders. Pregabalin is additionally approved for the treatment of fibromyalgia and neuropathic pain associated with diabetes mellitus or spinal cord injury. There are now more than 100 clinical trials examining the use of gabapentin perioperatively to reduce postoperative pain and a smaller but growing number of clinical trials examining the efficacy of pregabalin. As a body of work, they support the conclusion that perioperative use of gabapentinoids reduces early postoperative pain and opioid use.1–3 This article describes how this body of work may inform a surgeon’s or anesthesiologist’s optimization of perioperative use of gabapentinoids, including choice of agent, dose, timing, and duration of therapy. In addition, we described the less clear data for and against gabapentinoid efficacy in preventing the emergence of chronic postsurgical pain.

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