Ioanna Siafaka

gabapentin attenuates late but not acute pain after abdominal hysterectomy

Background and objective: Gabapentin has been suggested to decrease acute postoperative pain. We evaluated the effect of gabapentin on pain after abdominal hysterectomy. Methods: Sixty patients scheduled for abdominal hysterectomy were randomized to receive orally gabapentin 400 mg 6 hourly or placebo. Treatment started 18 h preoperatively and continued for 5 postoperative days. Pain (visual analogue score) and consumption of morphine for 48 h and of oral paracetamol/codeine were recorded after 2, 4, 8, 24 and 48 h and on days 3‐5 postoperatively. After 1 month, patients were interviewed by phone for pain, and analgesic intake after hospital discharge. Results: Morphine consumption (mean ± SD) was 35 ± 15.7 mg in the control and 28 ± 12.1 mg in the gabapentin group (P = 0.21). Median number (range) of paracetamol 500 mg/codeine 30 mg tablets taken during days 3‐5 was 1.0 (0‐6) in the control and 2.0 (0‐9) in the gabapentin group (P = 0.35). The visual analogue scores at rest and after cough did not differ between the two groups (F = 0.92, df = 1, P = 0.34 and F = 0.56, df = 1, P = 0.46, respectively). One month after surgery, 22/27 (81%) of the control group and 9/25 (36%) of the gabapentin group reported pain in the surgical area (χ2 = 11.15, P = 0.002), while 11/27 (41%) of controls and 7/25 (28%) of gabapentin patients consumed analgesics for pain (χ2 = 0.93, P = 0.39). The intensity of pain was decreased in the gabapentin group (χ2 = 12.6, P = 0.003). Conclusions: Gabapentin has no effect on immediate pain after abdominal hysterectomy but decreases pain 1 month postoperatively.

Pharmacological Treatment of Neuropathic Cancer Pain: A Comprehensive Review of the Current Literature

Abstract:  Neuropathic cancer pain (NCP), commonly encountered in clinical practice, may be cancer‐related, namely resulting from nervous system tumor invasion, surgical nerve damage during tumor removal, radiation‐induced nerve damage and chemotherapy‐related neuropathy, or may be of benign origin, unrelated to cancer. A neuropathic component is evident in about 1/3 of cancer pain cases. Although from a pathophysiological perspective NCP may differ from chronic neuropathic pain (NP), such as noncancer‐related pain, clinical practice, and limited publications have shown that these two pain entities may share some treatment modalities. For example, co‐analgesics have been well integrated into cancer pain‐management strategies and are often used as First‐Line options for the treatment of NCP. These drugs, including antidepressants and anticonvulsants, are recommended by evidence‐based guidelines, whereas, others such as lidocaine patch 5%, are supported by randomized, controlled, clinical data and are included in guidelines for restricted conditions treatment. The vast majority of these drugs have already been proven useful in the management of benign NP syndromes. Treatment decisions for patients with NP can be difficult. The intrinsic difficulties in performing randomized controlled trials in cancer pain have traditionally justified the acceptance of drugs already known to be effective in benign NP for the management of malignant NP, despite the lack of relevant high quality data. Interest in NCP mechanisms and pharmacotherapy has increased, resulting in significant mechanism‐based treatment advances for the future. In this comprehensive review, we present the latest knowledge regarding NCP pharmacological management.

Therapeutic management of chronic neuropathic pain : An examination of pharmacologic treatment

Abstract:  Neuropathic pain is defined as pain caused by a lesion in the nervous system and is common in clinical practice. Diagnosis can be difficult. Recommendations for first‐line pharmacologic treatments are based on positive results from multiple, randomized, controlled trials, and recommendations for second‐line pharmacologic treatments are based on the positive result of a single, randomized, controlled trial or inconsistent results of multiple, randomized, controlled trials. The results of published trials and clinical experience provide the foundation for specific recommendations for first‐line treatments, which include gabapentin, 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants (TCAs). Gabapentin (up to 3,600 mg/day) significantly reduced pain compared with placebo; improvements in sleep, mood, and quality of life were also demonstrated. Adverse effects of gababentin include somnolence and dizziness, and, less commonly, gastrointestinal symptoms and mild peripheral edema. Thus, monitoring and dosage adjustment are required, without discontinuation of the drug. Gabapentin combined with morphine achieved better analgesia at lower doses of each drug than each drug alone, with only mild adverse effects. The first medication that proved effective for neuropathic pain in placebo‐controlled trials was TCAs. Treatment decisions for patients with neuropathic pain can be difficult. Interest in the mechanisms and treatment of chronic neuropathic pain has increased during the past years, resulting in significant treatment advances in the future. In this article all recent knowledge on therapeutic management of chronic neuropathic pain is presented.

Postoperative Pain and Analgesic Requirements After Anesthesia with Sevoflurane, Desflurane or Propofol

BACKGROUND: General anesthetics may have nociceptive actions that affect postoperative pain. In studies evaluating postoperative pain, the effect of general anesthetics on analgesic requirements has not been considered except for one recent study suggesting that propofol anesthesia provides better analgesia after surgery than isoflurane. METHODS: In this prospective, blind, randomized trial we recorded postoperative analgesic requirements (mg of morphine) and pain scores (visual analog scale in mm) 2, 4, 8, and 24 h postoperatively in patients undergoing abdominal hysterectomy or myomectomy under sevoflurane, desflurane or propofol anesthesia, titrated to maintain Bispectral Index values between 35 and 45. Pain scores were also recorded immediately after transfer to the postanesthesia care unit. RESULTS: Cumulative morphine consumption did not differ among the three groups 2, 4, 8, or 24 h postoperatively (P = 0.50). The morphine consumed within 24 h postoperatively was 28 ± 13.8 mg in the sevoflurane group, 25 ± 11.7 mg in the desflurane group and 27 ± 16.1 mg in the propofol group. The visual analog scale values at rest or after cough immediately after patient transport to the postanesthesia care unit and 2, 4, 8, and 24 h after surgery did not differ among the three groups (P = 0.40, 0.39, 0.50, 0.47, 0.06 at rest and P = 0.67, 0.45, 0.22, 0.26, 0.29 after cough respectively). CONCLUSION: Morphine consumption and pain 24 h postoperatively did not differ among the sevoflurane, desflurane, and propofol groups.

Validation of the Dutch Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain

The Douleur Neuropathique 4 questionnaire (DN4) was developed by the French Neuropathic Pain Group and is a simple and objective tool, primarily designed to screen for neuropathic pain. The aim of our study is to validate the DN4 in the Greek language.

Pregabalin Vs. Opioids for the Treatment of Neuropathic Cancer Pain: A Prospective, Head-to-Head, Randomized, Open-Label Study

Neuropathic cancer pain (NCP) is a common manifestation of cancer and/or its treatment. Treatment following the WHO analgesic ladder provides relief for the majority of cancer pain patients; however, concern remains that opioids may be less efficacious for neuropathic pain (NP) compared with nociceptive pain, often necessitating the use of higher doses. Adjuvants, such as pregabalin, have shown to be efficacious for the treatment of NP, although data come mostly from noncancer studies. The comparative efficacy and safety of opioids versus adjuvants has not been studied for NCP. The aim of this study was to directly compare pregabalin versus a strong opioid for the treatment of NCP.

A randomized study of maternal serum cytokine levels following cesarean section under general or neuraxial anesthesia

BACKGROUND Cytokines are significant mediators of the immune response to surgery and also play a role in parturition. The aim of the study was to investigate the impact of the anesthetic technique for cesarean section on plasma levels of cytokines IL-6 and TNF-alpha. METHODS Thirty-five parturients scheduled for elective cesarean section were randomly assigned to general (n=18) or neuraxial (n=17) anesthesia. The general anesthesia group received thiopental 4 mg/kg, succinylcholine 1-1.5 mg/kg and 1% end-tidal concentration of sevoflurane in nitrous oxide and 50% oxygen. The neuraxial anesthesia group received intrathecal 0.5% levobupivacaine 1.8-2.2 mL and epidural fentanyl 1 microg/kg. Blood samples were taken for IL-6 and TNF-alpha immediately after positioning the parturient on the operating table, after uterine incision and before the umbilical cord clamping and 24h after surgery (T(1), T(2) and T(3) respectively). RESULTS The two groups did not differ in IL-6 (P=0.15) or TNF-alpha (P=0.73) serum concentrations at any time point. In the general and neuraxial anesthesia groups, IL-6 serum concentrations were significantly higher in the third blood sample, T(3) (12.2+/-5.0 and 15.2+/-4.3 pg/mL), than in T(1) (0.41+/-0.38 and 0.29+/-0.10 pg/mL) and T(2) (0.37+/-0.47 and 0.24+/-0.05) respectively (P<0.001). Within each group, serum TNF-alpha concentrations did not differ significantly over time (P=0.44). CONCLUSIONS Under the present study design anesthetic technique did not affect IL-6 or TNF-alpha concentrations in parturients undergoing elective cesarean section. Serum IL-6 levels increased 24 h postoperatively independently of anesthetic technique.

Accidental Epidural Injection of Vecuronium

IMPLICATIONS We report a case of accidental epidural injection of vecuronium in a female patient who underwent hemorrhoidectomy using epidural anesthesia. Because epidural injection of muscle relaxants may have serious side effects, immediate establishment of airway protection, monitoring of muscle relaxation, and follow-up for clinical signs of neurotoxicity are recommended.

Postoperative Pulmonary Function After Open Abdominal Aortic Aneurysm Repair in Patients With Chronic Obstructive Pulmonary Disease: Epidural Versus Intravenous Analgesia

BACKGROUND We reviewed our experience to determine the effect of epidural versus intravenous analgesia on postoperative pulmonary function and pain control in patients with chronic obstructive pulmonary disease (COPD) undergoing open surgery for abdominal aortic aneurysm. METHODS A retrospective study with prospective collection of data of 30 COPD patients undergoing open abdominal aortic aneurysm repair, during a 5-year period. Group I (n = 16) was operated under combined general and epidural anesthesia and epidural analgesia; group II (n = 14), under general anesthesia and intravenous analgesia. All patients performed pulmonary function tests (PFTs) preoperatively and during postoperative days 1 and 4. Pain assessment was performed on all patients during rest and activity on postoperative days 1, 2, and 4 by using the visual analog scale. Data were recorded for PFTs, postoperative pain, length of hospital stay, length of ICU stay, and postoperative pulmonary morbidity, including atelectasis and pulmonary infections. RESULTS There was no in-hospital mortality. Hospital stay was similar between the two groups (group I: 7.1 ± 1.0, group II: 7.5 ± 1.1). Group I patients showed significantly increased postoperative PFT values compared with group II patients at all time points (postoperative day 1: FEV(1)(%): 32.3 ± 4.4 vs. 27.1 ± 1.6, p = 0.007, FVC(%): 35.4 ± 8,5 vs. 28.3 ± 2.3, p = 0.035; postoperative day 4: FEV(1)(%): 50.4 ± 6.8 vs. 41.9 ± 6.8, p = 0.017, FVC(%): 51.3 ± 8.3 vs. 43.0 ± 7.9, p = 0.046). However, postoperative clinical pulmonary morbidity was not different between groups. Group I patients showed significantly reduced postoperative pain at all time points compared with group II patients. These differences were more pronounced during postoperative days 1 and 2, both at rest (visual analog score: 1.1 ± 0.9 vs. 2.6 ± 1.6, p = 0.02 and 0.7 ± 0.8 vs. 1.9 ± 1.1, p = 0.021, respectively) and during activity (2.3 ± 0.8 vs. 4.0 ± 1.7, p = 0.013 and 1.6 ± 0.7 vs. 2.8 ± 1.2, p = 0.019, respectively). CONCLUSIONS Epidural anesthesia and postoperative epidural analgesia improve the postoperative respiratory function, compared with general anesthesia and systemic analgesia, and reduce postoperative pain as well, in COPD patients undergoing elective infrarenal abdominal aortic aneurysm repair.

Modulation of synaptosomal plasma membrane-bound enzyme activity through the perturbation of plasma membrane lipid structure by bupivacaine

We investigated modulations of lipid dynamics and lipid-protein interactions of rat brain synaptosomal plasma membrane (SPM) as one of the possible mechanisms by which the local anesthetic bupivacaine (BPV) has an adverse effect on nerve cell function, with SPM-bound enzyme activity used as a functional probe. The kinetics of BPV impact on the activity of the endoenzymes Ca2+/Mg2+-stimulated ATPase and Na+/K+-stimulated ATPase and the active concentrations of the drug were relevant to those that produce biphasic systemic toxicity. Arrhenius plots of these enzymes showed a transition temperature of 26.6 +/- 1.8[degree sign]C and 24.5 +/- 1.2[degree sign]C (mean +/- SD), respectively, in control SPM, which shifted to 17.1 +/- 0.95[degree sign]C (P < 0.01) and 18.2 +/- 0.85[degree sign]C (P < 0.05) in SPM treated with 10-5 M BPV. The Hill coefficients for the allosteric inhibition of Ca2+/Mg2+-stimulated ATPase by Na+ and Na+/K+-stimulated ATPase by fluoride decreased from 1.73 +/- 0.20 and 1.95 +/- 0.25, respectively, in controls to 0.92 +/- 0.09 (P < 0.001) and 1.09 +/- 0.11 (P < 0.001) in the presence of 10-5 M BPV. The fluidity perturbation in the microenvironment of the ectoenzyme acetylcholinesterase was observed only at 5 x 10-3 M BPV, as confirmed by the disparity in transition temperature between the controls (22.3 +/- 1.2[degree sign]C) and the BPV-treated SPM (17.5 +/- 0.8[degree sign]C, P < 0.01) and that in the Hill coefficient in the two groups: 2.15 +/- 0.24 and 0.97 +/- 0.12 (P < 0.001), respectively. Implications: We propose that under physiological conditions, the neutral and protonated forms of local anesthetics can affect nerve cell function through the asymmetric perturbation of the membrane lipid structure, accompanied by synaptosomal plasma membrane-bound enzyme dysfunction. (Anesth Analg 1997;85:1337-43)