Alessandro Fabrizio Sabato

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.

Controlled-Release Oxycodone and Pregabalin in the Treatment of Neuropathic Pain: Results of a Multicenter Italian Study

Aims: The aim of our study was to compare the efficacy, safety, and quality of life of combination therapy with controlled-release (CR) oxycodone plus pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients with neuropathic pain. Materials and Methods: Patients with moderate to severe neuropathic pain, despite the use of various pharmacologic treatments prior to study entry, were enrolled (n = 409) and treated with CR oxycodone plus pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain intensity was rated on an 11-point numerical rating scale (NRS). Results: The combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were both more effective for alleviating neuropathic pain than pregabalin monotherapy (reduction in NRS value: 80, 76, and 46%, respectively; p ≤ 0.003). Significantly greater improvements from baseline in quality of life were reported with combination therapy than with monotherapy (p = 0.0009). At the end of treatment, the majority (91.2%) of patients receiving CR oxycodone plus pregabalin found that the treatment had been ‘effective’ or ‘very effective’. Combination therapy also allowed a dose reduction of both agents (22% for CR oxycodone and 51% for pregabalin) compared with the dosages of the respective monotherapies. Combination therapy had a superior safety profile compared with pregabalin monotherapy. Conclusions: The combination of CR oxycodone plus pregabalin may represent a valuable addition to the existing pharmacotherapy for neuropathic pain and warrants further investigation.

A Prospective Comparison of Continuous Wound Infiltration with Ropivacaine Versus Single-Injection Paravertebral Block After Modified Radical Mastectomy

BACKGROUND: The efficacy of continuous wound infiltration with local anesthetic has not been compared with that of thoracic paravertebral block (PVB) after breast surgery. In this study, we evaluated the analgesic efficacy and morphine consumption of the two techniques after mastectomy. METHODS: Forty-eight patients undergoing modified radical mastectomy with axillary dissection were randomly assigned to either a preoperative PVB with 20 mL of ropivacaine 0.5% (group PVB) or a continuous ropivacaine 0.5% infusion (CRI) at a 2 mL/h rate for each of two multilumen catheters placed subcutaneously at the end of the procedure (group CRI). The catheters were left in place for 24 h postoperatively. A standardized general anesthetic was administered to all patients. Postoperative morphine consumption, pain scores and painful restricted movement of the shoulder for 24 h postoperatively as well as incidence of adverse events, including postoperative nausea and vomiting, were recorded. RESULTS: Morphine consumption was similar between groups (PVB: 42.6 ± 11 vs CRI: 38.7 ± 11 mg in 24 h, P = 0.225). Absolute pain scores were low in both groups. Four hours after surgery, group PVB showed a significant reduction in postoperative pain (PVB: 0 [0–10] vs CRI: 0 [0–30], P = 0.002) and reduced painful restricted movement (P = 0.004), whereas the CRI group had lower pain scores (PVB: 10 [0–30] vs CRI: 0 [0–20], P = 0.034) and painful restricted movement (P = 0.043) 16 and 24 h (PVB: 10 [0–30] vs CRI: 0 [0–30], P = 0.012) after surgery. Postoperative nausea and vomiting was significantly more frequent in the CRI group (P = 0.017). CONCLUSIONS: Continuous wound infiltration of local anesthetics is an effective alternative to paravertebral analgesia after mastectomy with axillary dissection.

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).

Clinical and psychosocial correlates of post-herpetic neuralgia

Post‐herpetic neuralgia is the most challenging and debilitating complication of herpes zoster in the immunocompetent host. Because the effect of treatment is disappointing once the syndrome has developed, it is important to know which factors predict post‐herpetic neuralgia occurrence to facilitate selection of herpes zoster patients with a higher risk of developing neuralgia and undertake preventative strategies. The present study aimed at identifying demographic, clinical and psychosocial correlates of post‐herpetic neuralgia in a sample of 219 immunocompetent patients, who were examined by dermatologists in private practice in Italy and who completed a questionnaire designed to evaluate their clinical and psychosocial profile at the time of clinical diagnosis of herpes zoster and at a follow‐up visit 6 months later. In a univariate analysis, post‐herpetic neuralgia was associated significantly with older age, longer duration of prodromal pain, greater acute pain intensity, greater extent of rash, presence of abnormal sensations and use of systemic antiviral therapy. Compared to the values at herpes zoster onset, at the follow‐up visit patients with post‐herpetic neuralgia presented with similar high mean scores of pain intensity, anxiety and depression and greatly reduced quality of life, whereas patients without neuralgia presented with improved scores. In a multivariate model, older age, greater acute pain intensity, greater extent of rash and longer duration of prodromal pain were independently associated with post‐herpetic neuralgia. The results of this study may help physicians to identify patients with a higher risk of developing post‐herpetic neuralgia and undertaking preventative strategies. J. Med. Virol. 80:1646–1652, 2008.

Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis

OBJECTIVE To assess the efficacy and safety of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the N-acylethanolamines family, in reducing pain severity in patients with pain associated to different pathological conditions. METHODS This was an observational study conducted on 610 patients who were unable to effectively control chronic pain with standard therapies. PEA (600 mg) was administered twice daily for 3 weeks followed by single daily dosing for 4 weeks, in addition to standard analgesic therapies or as single therapy. The primary outcome measure was the mean score pain severity evaluated by the numeric rating scale. Safety was also evaluated. RESULTS PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without concomitant analgesic therapy. Importantly, PEA showed no adverse effects. CONCLUSIONS In this study, PEA was effective and safe in the management of chronic pain in different pathological conditions.

Continuous femoral nerve block provides superior analgesia compared with continuous intra-articular and wound infusion after anterior cruciate ligament reconstruction

Background and Objectives: This prospective, randomized, clinical trial compared pain intensity and analgesic drug consumption after anterior cruciate ligament (ACL) reconstruction with patellar tendon under femoral-sciatic nerve block anesthesia in patients who received either a continuous femoral nerve block (CFNB) or continuous local anesthetic wound and intra-articular infusions. Methods: Fifty patients were randomized to CFNB (n = 25) or an ON-Q device (I-Flow Corp, Lake Forest, Calif) (n = 25). All patients received sciatic nerve block (25 mL of ropivacaine 7.5 mg/mL and clonidine 30 &mgr;g). The first group received a CFNB (2 mg/mL of ropivacaine at 7 mL/hr), and the second group received a single-shot femoral nerve block (both using 25 mL of ropivacaine 7.5 mg/mL and clonidine 30 &mgr;g). At the end of the intervention, an ON-Q device was positioned on the ON-Q patients to continuously infuse the patellar tendon wound and intra-articular cavity with ropivacaine 2 mg/mL at 2 mL/hr for each catheter. Data regarding demographic, hemodynamic, pain scores, adverse effects, and need for supplemental analgesia were registered in a 36-hr follow-up period. Results: The CFNB group reported lower visual analog scale values than the ON-Q group: at rest at 12 hrs (2.4 [SD, 2.2] vs 5.4 [SD, 3.1]; P < 0.001) and on movement at 12 (3.1 [SD, 2.5] vs 6.3 [SD, 2.9]; P < 0.001) and 24 hrs (2.7 [SD, 1.9] vs 4.6 [SD, 2.6]; P = 0.01) after surgery. The number of morphine and ketorolac boluses was lower in the CNFB group (morphine: 3.2 [SD, 2.2] vs 6.2 [SD, 2.5]; P < 0.001; ketorolac: 1.1 [SD, 1.0] vs 2.4 [SD, 0.9]; P < 0.001). Conclusion: Continuous femoral nerve block provides better analgesia than the continuous patellar tendon wound and intra-articular infusions after anterior cruciate ligament reconstruction with patellar tendon.

Efficacy of Continuous Femoral Nerve Block With Stimulating Catheters Versus Nonstimulating Catheters for Anterior Cruciate Ligament Reconstruction

Background and Objectives: This prospective randomized controlled trial investigated the clinical efficacy of stimulating catheters for continuous femoral nerve block in patients who underwent anterior cruciate ligament reconstruction. Methods: Seventy patients were randomized to either a stimulating catheter (SC, n = 35) or a nonstimulating catheter (NSC, n = 35) for femoral nerve block using 25 mL ropivacaine 7.5 mg/mL and clonidine 50 &mgr;g injected through the catheter. A single-injection sciatic block was also given to ensure surgical anesthesia. The time to loss of sensation to cold and pinprick of the femoral nerve was registered as the onset time. Data were registered intra- and postoperatively regarding pain scores, adverse effects, and need for supplemental anesthesia and analgesia other than a continuous postoperative infusion of ropivacaine 2 mg/mL through the continuous femoral nerve catheter set at 7 mL/h. Results: Onset time was faster in the SC group (SC: 6.4 ± 2.5, NSC: 8.3 ± 2.9 min, P = .006). Visual analog scale pain scores were similar in both groups. The number of patient-controlled regional analgesia boluses (SC: 14.6 ± 12.6, NSC: 23.2 ± 13.6 mg ropivacaine 2 mg/mL, P = .008) as well as intravenous rescue ketorolac (SC: 34.3 ± 35.7, NSC: 54 ± 39.7 mg, P = .033) administered were higher in the NSC group. Conclusion: Although the use of a stimulating catheter was associated with faster onset time for the femoral nerve block and lower additional analgesics postoperatively, the clinical superiority (analgesia; lateral femoral cutaneous, and obturator nerve block) of stimulating catheters was not evident in this clinical setting.

No Evidence of Family History as a Risk Factor for Herpes Zoster in Patients with Post-Herpetic Neuralgia

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Risk factors include age, sex, ethnicity, exogenous boosting of immunity from varicella contacts, underlying cell‐mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. An association between herpes zoster and family history of zoster has been proposed. A case‐control study involving patients affected by post‐herpetic neuralgia, which usually follows more severe acute herpes zoster, was performed. The patients with post‐herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. The controls matched for sex and age were chosen among healthy subjects without a history of herpes zoster presenting at the Internal Medicine Outpatient Clinic for hypertension in the same time period. All the participants in the study gave informed consent and were interviewed by medically trained and blinded investigators using a questionnaire. Similar proportions of the patients and the controls reported a family history of herpes zoster irrespective of the degree of relationship, i.e., 17.4% and 18.2%, respectively, by analyzing only the first‐degree relatives [RR 1.03 (CI 95%: 0.78–1.37)], and 28.4% and 29.6%, respectively, by analyzing the total number of relatives [RR 1.03 (CI 95%: 0.81–1.31)]. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings. J. Med. Virol. 82:1007–1011, 2010.

Italian Oncological Pain Survey (IOPS) A Multicentre Italian Study of Breakthrough Pain Performed in Different Settings

Objective:A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC). Methods:A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings. Results:1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs. Conclusion:This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient’s quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics.