Long-term controlled-release oxycodone and pregabalin in the treatment of non-cancer pain: an observational study.

AIMS: This study evaluates the efficacy and tolerability of long-term controlled-release (CR) oxycodone + pregabalin in patients with non-cancer pain, in a real-life setting. METHODS: Patients (n = 1,051) with chronic uncontrolled non-cancer pain received CR oxycodone + pregabalin for 1 year. Pain intensity was rated on an 11-point numerical rating scale (NRS) at months 1, 2, 4, 6, 9 and 12. RESULTS: Throughout the study period, the NRS score decreased significantly (baseline: 7.02 ± 1.26; 12 months: 1.45 ± 0.92; p = 0.00001). Following an initial increase in the mean daily doses of CR oxycodone (starting dose: 12.5 ± 8.4 mg) and pregabalin (starting dose: 121.7 ± 97.2 mg), dose reductions were seen for both drugs with the trend particularly evident for CR oxycodone. 23% of patients withdrew from the study, mainly due to adverse events (67.9% of withdrawn subjects). However, 19.7% of withdrawn patients were removed from the study due to complete relief from chronic pain. The combination was generally well tolerated and there were no reports of addiction. CONCLUSION: The combination of CR oxycodone + pregabalin could represent a valuable long-term therapeutic addition to existing pharmacological options for the treatment of non-cancer pain.

Postoperative pain treatment SIAARTI Recommendations 2010. Short version.

The aim of these recommendations is the revision of data published in 2002 in the "SIAARTI Recommendations for acute postoperative pain treatment". In this version, the SIAARTI Study Group for acute and chronic pain decided to grade evidence based on the "modified Delphi" method with 5 levels of recommendation strength. Analgesia is a fundamental right of the patient. The appropriate management of postoperative pain (POP) is known to significantly reduce perioperative morbidity, including the incidence of postoperative complications, hospital stay and costs, especially in high-risk patients (ASA III-V), those undergoing major surgery and those hospitalized in a critical unit (Level A). Therefore, the treatment of POP represents a high-priority institutional objective, as well as an integral part of the treatment plan for "perioperative disease", which includes analgesia, early mobilization, early enteral nutrition and active physiokinesitherapy (Level A). In order to improve an ACUTE PAIN SERVICE organization, we recommend: --a plan for pain management that includes adequate preoperative evaluation, pain measurement, organization of existing resources, identification and training of involved personnel in order to assure multimodal analgesia, early mobilization, early enteral nutrition and active physiokinesitherapy (Level A); --the implementation of an Acute Pain Service, a multidisciplinary structure which includes an anesthetist (team coordinator), surgeons, nurses, physiotherapists and eventually other specialists; --referring to high-quality indicators in establishing an APS and considering the following key points in its organization (Level C): --service adoption; --identifying a referring anesthetist who is on call 24 hours a day; --patient care during the night and weekend; --sharing, drafting and updating written therapeutic protocols; --continuous medical education; --systematic pain assessment; --data collection regarding the efficacy and safety of the implemented protocols; --at least one audit per year. --a preoperative evaluation, including all the necessary information for the management of postoperative analgesia (Level C); --to adequately inform the patient about the risks and benefits of drugs and procedures used to obtain the maximum efficacy from the administered treatments (Level D). We describe pharmacological and loco-regional techniques with special attention to day surgery and difficult populations. Risk management pathways must be the reference for early identification and treatment of adverse events and chronic pain development.

Opioid-related bowel dysfunction: prevalence and identification of predictive factors in a large sample of Italian patients on chronic treatment.

BACKGROUND AND OBJECTIVES: Opioid-bowel dysfunction (OBD) is a broad range of symptoms potentially associated with opioid therapy. This prospective, multicentric study assesses the prevalence of OBD in patients on analgesic therapy for the treatment of pain from any cause and identifies the factors associated with the onset of this side effect. MATERIALS AND METHODS: Consecutive patients aged > 18 years, on analgesic treatment with opioids, non-steroidal anti-inflammatory drugs (NSAIDs) or other therapies for chronic pain of any aetiology were included in the study. The association of OBD with gender, age, pain aetiology and analgesic treatment was analyzed by multivariate analysis and logistic analysis. RESULTS: In total, 2324 patients were included in the study. The prevalence of OBD symptoms was 63.5%, despite that the wide majority of patients (89.5%) were receiving laxatives. OBD symptoms were judged as directly correlated with analgesic therapy in 85.1% of cases. The highest prevalence of constipation was reported with morphine, whereas the lowest was observed in patients on oxycodone CR and buprenorphine TTS. Statistical analysis showed that patients on opioids have a higher likelihood of experiencing OBD symptoms than those on NSAIDs or other treatments (66.2% vs 37.0%), and this probability is even higher in those with cancer-related pain (69.3%). Female gender and age > 70 years also appeared as risk factors. The logistic analysis indicated that cancer-related pain, increased age and the use of fentanyl are positive predictors of the presence of OBD, whereas the administration of oxycodone CR was associated with a decreased incidence of these symptoms. DISCUSSION: Even with the limitation of any observational experience, this study suggests, for the first time, the existence of some factors predictive of the onset of OBD symptoms in patients on analgesic treatment. Moreover, different opioids seem to be associated with a different risk of experiencing these symptoms.

Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences.

BACKGROUND: Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of clinical trials indicate that gabapentin and pregabalin could be effective as postoperative analgesics. This systematic-narrative review aims to analyse the most recent evidences regarding the effect of gabapentinoids on postoperative pain treatment. METHODS: Medline, The Cochrane Library, EMBASE and CINHAL were searched for recent (2006-2009) randomized clinical trials (RCTs) of gabapentin-pregabalin for postoperative pain relief in adults. Quality of RCTs was evaluated according to Jadad method. Visual analogue scale (VAS), opioid consumption and side-effects (nausea, vomiting, dizziness and sedation) were considered the most important outcomes. RESULTS: An overall of 22 gabapentin (1640 patients), 8 pregabalin (707 patients) RCTs and seven meta-analysis were involved in this review. Gabapentin provided better post-operative analgesia and rescue analgesics sparing than placebo in 6 of the 10 RCTs that administered only pre-emptive analgesia. Fourteen RCTs suggested that gabapentin did not reduce PONV when compared with placebo, clonidine or lornoxicam. Pregabalin provided better post-operative analgesia and rescue analgesics sparing than placebo in two of the three RCTs that evaluated the effects of pregabalin alone vs placebo. Four studies reported no pregabalin effects on preventing the PONV. CONCLUSION: Gabapentin and pregabalin reduce pain and opioid consumption after surgery in confront with placebo, but comparisons with other standard post-operative regimens are not sufficient. Gabapentin and pregabalin seem not to have any influence on the prevention of PONV.

Scrambler therapy.

UNLABELLED: In neuropathies there are complex reactions that modify the homeostatic equilibrium of pain system. In such a context the Scrambler Therapy (ST5) interferes with pain signal transmission, by ''mixing'' a ''non-pain'' information into the nerve fibres. The aim of this study is to evaluate the effectiveness of ST5 in the treatment of neuropathic pain. The ST5 consists of a multiprocessor apparatus able to simulate 5 artificial neurons by the application of surface electrodes on skin pain areas. A total of 226 patients, all suffering from intense drug-resistant neuropathic pain, were recruited for this trial in 2004. INCLUSION CRITERIA: neuropathic pain, very high baseline visual analogue scale (VAS). EXCLUSION CRITERIA: pacemaker users, neurolithic blocks or neurolesive pain control treatment. The treated neuropathic pain syndromes were: failed back surgery syndrome (FBSS), sciatic and lumbar painpost-herpetical (PHN), trigeminal neuralgia, post-surgery nerve lesion neuropathy, pudendal neuropathy, brachial plexus neuropathy, low back pain (LBP), others. The trial programme: 1 to 6 therapy sessions of 5 treatments, each one lasting 30 min. Pain intensity was evaluated using VAS before and after each treatment. The statistical significance of VAS was measured using the paired t-test. The total results show 80.09% of responders (pain relief>50%), 10.18% of partially responders (pain relief from 25% to 49%) and 9.73% of no responders (patients with pain relief<24% or VAS>3). The CONCLUSIONS: is draen that ST5 produced a statistically significant (P<0.0001) pain relief in all treated neuropathies.

Intentional lateral epidural catheter placement for anterior cruciate ligament reconstruction.

BACKGROUND: Unilateral epidural block might constitute a clinical option in lower limb orthopedic surgery. METHODS: Seventy-five patients undergoing anterior cruciate ligament reconstruction (ACLR) were randomized to either a laterally directed epidural catheter (IUEC, n = 40) or a classic midline catheter (CMEC, n = 35). Paresthesia encountered during catheter insertion was registered. The start dose of the anesthetic mixture clonidine 60 microg (0.4 ml), sufentanil 15 microg (0.3 ml) and ropivacaine 10 mg ml(-1)(10.3 ml) in 11 ml of total volume) was set at 5 ml and was increased by 2 ml if anesthesia was inadequate after assessment for sensory blockade to cold and pin-prick. Data were registered intra- and postoperatively regarding pain scores as well as motor block, hemodynamic parameters, adverse effects and need for supplemental analgesia other than a continuous postoperative epidural infusion. RESULTS: In the IUEC group 80% of patients reported a light paresthesia of the affected side during catheter insertion, whereas 71% of patients in the CMEC group reported no paresthesia at all. The amount of anesthetic used to establish surgical anesthesia was lower in the IUEC group (6.2 +/- 0.8 vs. 8 +/- 1.9 ml, P < 0.001). Motor block (Bromage score) of the unaffected side was significantly lower in the IUEC group (P < 0.001). Pain intensity scores, hemodynamic parameters, and supplemental analgesia given were similar between the two groups except for VAS scores at 12 h postoperatively, which were higher in the CMEC group (P < 0.01). Urinary retention was significantly more frequent in the CMEC group (19/35 vs. 5/40, P < 0.001). CONCLUSION: These results suggest that the IUEC technique is a feasible and efficient method for providing anesthesia and analgesia for ACLR and is associated with a lower consume of anesthetics, less motor block and a reduced incidence of urinary retention.

Combined general and epidural anesthesia with ropivacaine for renal transplantation.

AIM: To evaluate the effectiveness and safety of epidural ropivacaine anesthesia in association with light general anesthesia during renal transplantation and compare epidural and endovenous analgesia techniques for postoperative pain control. EXPERIMENTAL DESIGN: prospective randomized study. SETTING: Organ Transplantation Center, Department of Surgery, "Tor Vergata" University of Rome, St. Eugenio Hospital, Rome. PATIENTS: 25 patients affected by chronic renal failure were enrolled in this study. Thirteen constituted the combined epidural-general anesthesia group (EPI-GEN), mean age 40.15+/-9.81 years; while the others constituted the general anesthesia group (GEN), mean age 46.75+/-7.45 years. Operation: cadaveric renal transplantation. Group EPI-GEN: epidural anesthesia performed with 12-15 ml of a ropivacaine 0.75% and fentanyl 5 microg/ml solution followed by light intravenous or inhalatory general anesthesia and postoperative epidural analgesia with ropivacaine 0.2% and fentanyl 2 mg/ml. Group GEN: inhalatory or intravenous general anesthesia and intravenous tramadol postoperative analgesia. MEASUREMENTS: hemo-dynamics, renal function, arterial blood gases analysis, acid-base balance and postoperative pain data was collected and examined. RESULTS: Postoperative epidural analgesia resulted significantly more effective than intravenous tramadol. PaO(2)/FiO(2) ratio was significantly higher in group EPI-GEN patients both on awakening and throughout postoperative observation. Hemodynamics and renal function did not appear to differ significantly. CONCLUSION: Combined epidural-general anesthesia is as valid a technique as any for renal transplantation; however postoperative epidural ropivacaine analgesia resulted more effective than intravenous tramadol. Respiratory function appeared less affected, facilitating a fast and uncomplicated postoperative recovery.

Comparison of epidural, continuous femoral block and intraarticular analgesia after anterior cruciate ligament reconstruction.

BACKGROUND: The purpose of this study was to compare three locoregional techniques of pain management after arthroscopic anterior cruciate ligament reconstruction (ACLR). METHODS: Sixty ASA I-II subjects were enrolled after obtaining written informed consent. Patients were randomly allocated to three groups of 20 subjects. The first group (EPI) received epidural ropivacaine 0.2% plus sufentanil 0.2 micro g ml-1, at 5 ml h-1. Patients in the second group (CFB) were given a continuous infusion of the same analgesic mixture through a femoral catheter. The third group (IA) received a continuous intraarticular infusion of ropivacaine 0.2% plus sufentanil 0.2 micro g ml-1, at 5 ml h-1. All subjects were allowed PCA boluses of 5 ml of local anesthetic. Analgesia was assessed for 36 h after the end of surgery by means of a visual analog scale (VAS) and a verbal scale (VS), as well as the number of PCA boluses administered and the amount of supplementary i.v. ketorolac, if given. RESULTS: The VAS and VS scores were significantly higher in group IA during the 24 h following surgery. Ketorolac requirement was higher in group IA throughout the postoperative observation. Adverse effects were similar in all groups except for urinary retention, which was significantly more frequent in group EPI. CONCLUSIONS: We conclude that either epidural or continuous femoral nerve block provide adequate pain relief in patients who undergo ACLR, whereas intraarticular analgesia seems unable to cope satisfactorily with the analgesic requirements of this surgical procedure.

Curariform peripheral block of muscular tone selectively increases precentral N30 somatosensory evoked potentials component. A pharmacological study carried out on healthy subjects and parkinsonian syndromes.

In the present study we investigated whether the precentral component (N30) of short somatosensory evoked potentials (SEPs) to median nerve stimulation may be modified by peripheral neuromuscular blocking agent in patients affected by rigidity. We, therefore, recorded SEPs in nine Parkinson's disease (PD) patients and in seven psychotic patients affected by neuroleptic malignant syndrome (NMS), all showing severe rigidity. Each patient group was studied before and after the placebo, and before and after an atracurium besilate bolus of 0.05 mg/kg, in a single recording session. At the time of the test the PD patients had not taken any antiparkinsonian therapy for at least 48 h. The same recordings were also taken on nine neurologically normal subjects undergoing surgical procedures. Atracurium administration produced a remarkable amplitude increase of the major precentral component (N30) of SEPs. An atracurium-induced N30 amplitude increase was observed in both PD patients (from 2.41 to 4.07 microV) and NMS psychotic patients (from 2.03 to 3.97 microV), whereas there was a minor N30 amplitude increase in healthy subjects (from 3.53 to 4. 10 microV). The N30 latency was unaffected. Amplitude and latency of the major parietal SEPs component (N20) was unchanged in the three groups studied. Our results lead to the conclusion that a neuromuscular blocking agent is capable of increasing the N30 amplitude in patients affected by severe rigidity, exclusively reducing their muscular tone without interfering with the central dopaminergic system. Thus, a "peripheral gating" of sensory input to the supplementary motor area due to rigidity may play a relevant role in producing the N30 amplitude decrease described in patients affected by degenerative or pharmacologically induced parkinsonism. The reduction of rigidity could be the mechanism by which dopamine may increase the precentral N30 amplitude in parkinsonian syndromes.

Unilateral thoracoscopic reduction pneumoplasty for asymmetric emphysema.

OBJECTIVE: We prospectively analyzed the surgical and functional results of unilateral thoracoscopic reduction pneumoplasty which we performed by choice in patients with asymmetric emphysema. METHODS: Between October 1995 and June 1997, 119 emphysematous patients were examined and 34 were operated upon. Among these, 14 selected patients with asymmetric distribution of emphysema in the lungs underwent unilateral reduction pneumoplasty (ten right, and four left). There were 13 males and one female, with a mean age of 62 years. Eligibility criteria included bullous and non-bullous end-stage emphysema with severe limitation to daily activity. RESULTS: No patient required conversion to thoracotomy. Mean operative time ranged between 70 and 240 min with a mean of 103 min. There was no postoperative mortality but five patients developed one or more complications: five prolonged air leaks (>7 days); two pulmonary infections; one empyema. No patient required postoperative mechanical ventilation. Median hospital stay was 8 days. At the 3-month follow-up the mean FEV1 increased from 0.8 l to 1.2 l (P < 0.001). Mean FVC increased from 2.6 l to 2.9 l (P < 0.001). The Medical Research Council dyspnea score decreased from a mean of 3.2 to 1.8 (P < 0.001). CONCLUSIONS: Asymmetric distribution is a frequent finding in patients with severe emphysema. Unilateral thoracoscopic reduction pneumoplasty may represent an ideal approach in this selected group of patients.

Adjuvant pneumomediastinum in thoracoscopic thymectomy for myasthenia gravis.

To facilitate initial visualization and subsequent mobilization of the thymus, adjuvant pneumomediastinum was preoperatively induced in 4 patients who underwent video-assisted thoracoscopic thymectomy. Neither mortality nor technique-related morbidity was observed. This experience shows video-assisted thoracoscopic thymectomy to be a safe and reliable procedure. In addition, we believe that adjuvant pneumomediastinum seems to facilitate the dissection maneuvers and could shorten operative time.

Biochemical changes in neurosurgical patients under critical care treated with mannitol.

A Study was carried out on ten patients undergoing operations for brain tumors, who were treated with mannitol solutions. This caused a significant depletion of serum sodium ion and in an increase of discriminate osmolality (to 60 mosM/kg H2O). A hypothesis about the particular biochemical mechanism, involving the electrolyte and water distribution, is presented.