Effect Of Pregabalin Research Articles

The Effect Of The Use Of Pre-Emptive Oral Pregabalin On The Postoperative Spinal Analgesia In Patients Presented For Orthopedic Surgeries: Randomized Controlled Trial.

BackgroundPreoperative oral pregabalin could improve postoperative analgesia and prevent chronic pain development. The aim of this study is to evaluate the effect of oral pregabalin on the duration and quality of postoperative analgesia in spinal anesthesia.MethodsSixty adult patients presented for internal fixation of femoral fracture under spinal anesthesia were included in the study. They were randomly distributed to a placebo group and a pregabalin group receiving 150 mg pregabalin capsules 1 hr before surgery. The onset, duration, and regression of sensory and motor block were recorded. Rescue analgesia consumption, postoperative pain score, and quality of sleep were also assessed.ResultsOral pregabalin significantly prolonged the time to two-segment regression of sensory block, reaching 86.67±17.88 mins, the time required to regression of spinal block to L2, reaching 155.33± 34.71 mins, and the duration of motor block, reaching 138 ± 23.5 mins, with no effect on the onset of sensory or motor block (P = 0.60 and 0.62). It significantly decreased the VAS score 4 hrs, 6 hrs, and 12 hrs postoperatively, prolonged the duration of postoperative analgesia, reaching 392.00±47.23 mins, and decreased morphine consumption to 7.67±3.65 mg. It also improved the quality of sleep in the first night after surgery.ConclusionPreemptive oral pregabalin prolonged the time to the first request for postoperative analgesics and improved sleep in the first night after surgery.

The effect of gabapentin and pregabalin on bone turnover and bone strength: A prospective study in Wistar rats.

There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.

Investigating the possible pain attenuating mechanisms of pregabalin in chronic constriction injury-induced neuropathic pain in rats

Aim of the study: The current study was aimed to investigate the neuropathic pain attenuating mechanism of pregabalin using chronic constriction injury (CCI) model in rats.Material and Methods: The sciatic nerve was ligated by placing four loose ligatures around it to induce neuropathic pain. The pain development in terms of cold allodynia, mechanical hyperalgesia, and heat hyperalgesia was assessed on the 7th and 14th day after surgery, using acetone drop, pinprick, and hot plate tests. On the 14th day after the injury, pain parameters were assessed 30 minutes after administration of pregabalin (30 mg/kg) and sodium nitroprusside (5 mg/kg) in CCI-subjected rats.Results: CCI led to induction of neuropathic pain, which was more prominent on 14th day in comparison to 7th day. A single administration of pregabalin and sodium nitroprusside on 14th day, markedly reduced pain parameters and increased serum nitrite levels. Pretreatment with L-NAME abolished neuropathic pain attenuating effects of pregabalin suggesting that pregabalin may increase the levels of nitric oxide to mitigate neuropathic pain. Pretreatment with naloxone significantly abrogated pain attenuating effects of pregabalin and sodium nitroprusside in CCI-subjected rats suggesting that pregabalin and nitric oxide-mediated analgesic action are mediated through release of endogenous opioids. Moreover, naloxone failed to modulate pregabalin-induced increase in nitric oxide levels suggesting that the opioid system does not control the nitric oxide levels, and opioids may be downstream modulators of nitric oxide.Conclusion: Pregabalin may increase the release of nitric oxide, which may increase the release of endogenous opioids to attenuate neuropathic pain in CCI subjected rats.

Preemptive use of oral gabapentin or pregabalin for acute postoperative pain following lower limb orthopaedic surgery under spinal anaesthesia

Background: Postoperative pain is a major cause of perioperative morbidity and functional impairment. Preemptive analgesia is an analgesia regimen instituted before the surgery, to desensitize the pain pathways. Pregabalin and gabapentin have been claimed to be effective in reducing postoperative pain without significant alterations in hemodynamics.
 Objectives: This study was conducted to compare the effectiveness of pregabalin and gabapentin in reducing postoperative pain, total opioid consumption, postoperative nausea and vomiting and sedation in patients undergoing lower limb orthopaedic surgeries under spinal anaesthesia.
 Methodology: Eighty patients undergoing lower limb orthopaedic surgeries under spinal anaesthesia were divided into two groups, to either receive 300mg gabapentin or 150mg pregabalin, one hour before surgery. The patients were evaluated at one, two, six, 12 and 24 hours postoperatively and Visual Analogue Scale score for pain, postoperative nausea vomiting, and sedation score were monitored. Tramadol 50 mg was used as rescue analgesic and total consumption over 24 hours was recorded.
 Results: The mean duration of postoperative analgesia was significantly higher with pregabalin (282±106 minutes versus 234 ± 97minutes, p=0.009). The sedation score was significantly higher with pregabalin in the first hour (p=0.001). The total tramadol consumption was higher with gabapentin; however, it was statistically insignificant. The occurrence of postoperative nausea and vomiting was comparable between the groups. Minor adverse effects such as dizziness, sedation and headache were observed in both groups.
 Conclusion: Pregabalin 150 mg orally significantly increases the duration of postoperative analgesia than gabapentin 300mg following lower limb orthopaedic surgeries. Although sedation is frequently observed, it doesn’t alter the hemodynamics and thus, may be used safely.

Evaluation of opioid sparing effect of dexmedetomidine and pregabalin using acute pain model in male wistar rats

Background: Adjuvant analgesics are added to pain management regimen to reduce opioid consumption and minimise their side effect. Newer ones like dexmedetomidine and pregabalin have not been thoroughly researched. Objectives of the study to study the opioid sparing effect of dexmedetomidine and pregabalin using tail flick and hot plate method in male wistar rats.Methods: Forty two rats were grouped into seven groups with six in each group. Analgesic activity was tested using tail flick, where in the reaction time to flick its tail on a heated surface was noted. In the hot plate method, the reaction time to withdraw or lick the paws when placed on heated surface was noted.Results: The reaction time to flick its tail was prolonged with dexmedetomidine and pregabalin when combined with opioids even in sub therapeutic doses.Conclusion: Adjuncts like dexmedetomidine and pregabalin can be very useful in mutimodal pain management and also to reduce the opioid consumption.

Effect of Single Dose of Pregabalin on Post Tracheal Intubation Sore Throat after General Anesthesia

Background: Sore throat is one of the major complications of tracheal intubation after general anesthesia. Pregabalin is an analgesic, the anti neuropathic pain and analgesic effects of which have been demonstrated in various studies. This study examined the effects of single dose pregabalin one hour before tracheal intubation, to prevent sore throat after extubation. Methods: In a double-blind, randomized clinical trial, 60 patients who had undergone general and urologic surgeries at Imam Reza hospital in Tabriz, Iran, since March to July 2015 that required tracheal intubation, were included in the study. The patients were randomly divided into two groups (group A, 30 patients and group B, 30 patients). In the group A, an hour before anesthesia, one pregabalin tablet (300mg) was given to the patients. For the patients of the group B, the placebo was given. After awareness of patients, the severity of sore throat was measured and recorded by VAS scale after 2, 6 and 24 hours of the surgery. Results: Severity and incidence of sore throat after tracheal intubation were not significantly different between two groups. Meanwhile, no side effects of pregabalin were observed in the group A. Conclusion: Administration of pregabalin as a single dose of 300 mg one hour prior to anesthesia and intubation decreased the incidence and severity of sore throat in the case group than the control group, although the amount of this reduction was not statistically significant between the two groups.

Effect of Pregabalin on Perioperative Headache in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized Double-Blind, Placebo-Controlled Trial.

Background Patients with acute aneurysmal subarachnoid hemorrhage (aSAH) experience excruciating headache that is difficult to manage in resource-constrained settings. Pregabalin’s (β-isobutyl-GABA) analgesic, antiepileptic, and antiemetic properties make it an attractive adjuvant in pain management for these patients. Methods We conducted a double-blind, placebo-controlled, randomized clinical trial on 40 aSAH patients undergoing aneurysmal clipping to assess the effect of perioperative pregabalin in decreasing perioperative headache, anesthetic, and opioid requirement. Patients received either pregabalin (75 mg) or placebo twice daily soon after admission till 24-hour postoperative, in addition to paracetamol 650 mg thrice daily. Headache assessed using a visual analog scale (VAS) at five time points was compared using a mixed effects regression model. Results Pain assessed by VAS declined significantly more from the baseline in pregabalin recipients compared with placebo at preinduction (–3.6 vs.–1.8; p = 0.004), 12-hour (4.3 vs. 2.8; p = 0.014), and 24-hour postsurgery (4.7 vs. 2.9; p = 0.007), but not at the 6-hour postoperation (4.9 vs. 3.8; p = 0.065). Pregabalin recipients required a lower minimum alveolar concentration of sevoflurane to maintain a prespecified bispectral index of 40 and 60 (0.8 vs. 0.9; p = 0.014) and required fewer rescue analgesic doses in the 24 hours following surgery (1.8 vs. 3.3; p = 0.005). The intraoperative fentanyl requirement was not significantly different between the groups (10 μg/kg vs. 11.4 μg/kg; p = 0.065). There was no significant difference in the sedation scores. Conclusions Pregabalin 75 mg administered twice daily, during the perioperative period, was an effective adjunct in the management of the severe headache experienced by patients with aSAH and decreased the opioid and anesthetic requirement without significantly increasing sedation.

Preemptive analgesia after lumbar spine surgery by pregabalin and celecoxib: a prospective study.

ObjectiveTo evaluate the preemptive analgesic effect of combination pregabalin with celecoxib for lumbar spine surgery.MethodsA prospective, randomized study was conducted among 60 lumbar spine surgery patients and divided into two groups. Postoperative pain relief was achieved with intravenous patient-controlled analgesia with morphine. The preemptive analgesia group received oral pregabalin (150 mg) and celecoxib (200 mg) 2 hrs before surgery, and the control group received a placebo. Pain was assessed by visual analogue scale (VAS). Side effects and morphine consumption were monitored until 48 hrs after surgery.ResultsVAS score at rest and during movement was statistically significantly lower in the preemptive analgesia group at most time points (p<0.05). Morphine consumption was significantly lower in the preemptive analgesia group compared with control group in the 24 first hours (29.03±4.38 mg vs 24.43±4.94) and 48 hrs (52.23±9.57 mg vs 44.20±10.21 mg), p<0.05. Hemodynamics, respiratory rate, and SpO2 were similar for both groups. The sedation score was only statistically significant at H8 time point. The incidence of nausea/vomiting in the preemptive group did not statistically differ from the control group.ConclusionPreoperative administration of pregabalin combined with celecoxib had a good preemptive analgesia effect and reduced intravenous morphine consumption after lumbar spine surgery. Side effects were mild and transient.

Pregabalin-induced urticarial rash and neutropenia in a renal transplant recipient: a case report

BackgroundPregabalin is a medication used to treat epilepsy, neuropathic pain and generalised anxiety disorder. The most common side effects of pregabalin include dizziness, drowsiness, weight gain, ataxia and diplopia. On the other hand, neutropenia and rash are rare side effects of pregabalin, and at the time of writing, there are only two documented cases of neutropenia and one of rash in the literature, none of which involved renal transplant recipients.Case presentationWe present a 37-year-old renal transplant recipient who was admitted with lethargy, sore throat, urticarial rash and neutropenia after recently being commenced on pregabalin. On physical examination, he had erythematous urticarial rash near his renal transplant scar, on his right elbow, left knee and left wrist. Bacterial/viral serology and immunology were all negative. A blood film confirmed neutropenia and revealed reactive lymphocytes and neutrophil left shift, and those features were compatible with drug reaction. After cessation of the pregabalin, the neutropenia resolved. No other causes of neutropenia or urticarial rash were identified.ConclusionTo the best of our knowledge, we have described the first case of concomitant pregabalin-induced neutropenia and urticarial rash in a kidney transplant patient. This case report highlights the importance of close monitoring when starting any new medications, particularly in the immunosuppressed population, and is relevant because of the growing usage of pregabalin for treating neuropathic pain in such patients and the risk that a missed pregabalin-related neutropenia could lead to unnecessary modifications of the immunosuppressive treatment.

Skilled reaching deterioration contralateral to cervical hemicontusion in rats is reversed by pregabalin treatment conditional upon its early administration.

Introduction:Gabapentinoids are first-line treatments for painful traumatic and nontraumatic central nervous system disorders. Evidence from a large human study suggests that early use of gabapentinoids after spinal cord injury improves motor scores. The underlying mechanism is unknown.Objectives:We sought to examine the effects of early pregabalin (PGB, a gabapentinoid) treatment on performance in a fine motor task (skilled reaching) after cervical hemicontusion. We also asked whether early PGB administration affected PGB responsiveness later on.Methods:Rats received C4/5 cervical hemicontusions. Injury severities ranged from 80 to 150 kdyn. We monitored evidence of skin irritation (peri-incisional and elsewhere) and quantified food pellet retrieval using the Montoya staircase test. Behaviours were assessed in rats receiving early (for 3 weeks from injury induction) and/or late (resuming or beginning at week 8) PGB treatment in animals with 150-kdyn injuries.Results:Contralateral skilled reaching waned in control animals with 150-kdyn injuries. This was prevented in animals, which received early PGB as long as treatment continued. Deterioration of skilled reaching was reversed by later (week 8) PGB only in animals that had received early treatment. Ipsilateral reaching impairment was not improved by PGB. Relief of skin irritation verified early PGB efficacy.Conclusion:Hemicontusive spinal cord injury produces a contralateral motor phenotype evocative of on-going neuropathic pain. Early PGB preserves sensitivity to subsequent PGB treatment, indicating that motor function is impaired by neuropathic pain and can be improved indirectly by early PGB administration. Direct effects of PGB on motor circuitry cannot be excluded but are not supported by our data.

Effectiveness of pregabalin for treatment of chronic cervical radiculopathy with upper limb radiating pain: an 8-week, multicenter prospective observational study in Japanese primary care settings.

Background: Despite high prevalence of chronic neck pain in Japan and the negative impact pain has on patient’s quality of life (QoL), the therapeutic value of pregabalin for chronic neck pain with a neuropathic pain (NeP) component has not been assessed in a typical Japanese health care setting.Methods: An 8-week, non-interventional, multicenter, observational study of Japanese adults (≥20 years) with chronic refractory cervical pain including a NeP element (for ≥12 weeks) and sleep disturbance on the Pain-Related Sleep-Interference Scale (PRSIS) ≥1 (from 0 “does not interfere with sleep” to 10 “completely interferes”). Patients received either usual care with conventional analgesics or pregabalin (150–600 mg/day) for 8 weeks. “Usual care” with analgesics or other treatment(s) was determined based on physician’s best clinical judgment. Primary endpoint was change from baseline to week 8 in PRSIS. Secondary endpoints included: change from baseline to week 4 in PRSIS, and to week 4 and 8 in pain Numerical Rating Scale (NRS; from 0 “no pain” to 10 “worst possible pain”), and on the Neck Disability Index (NDI). Other assessments of QoL were undertaken. Safety was monitored.Results: Overall, 369 patients received pregabalin (n=145) or usual care (n=224). The median (range) dose of pregabalin was 49.6 (25.0–251.5) mg/day. Least-squares mean change in PRSIS from baseline to week 8 favored pregabalin (–1.167 vs –0.269; treatment difference –0.898 [95% CI –1.262, –0.535], P<0.001). Similar observations were seen at week 4 in favor of pregabalin versus usual care (P<0.001). Pregabalin significantly improved pain NRS and NDI scores at weeks 4 and 8 (all P<0.001). Improvements in QoL versus usual care were also observed. Pregabalin was generally well tolerated.Conclusion: In this open-label study, pregabalin improved PRSIS and resulted in clinically meaningful reductions in pain in Japanese patients with NeP associated with chronic cervical pain.ClinicalTrials.gov identifier: NCT02868359.

Cardiovascular Safety of Gabapentinoids

The objective of this manuscript is to describe the cardiovascular effects of the gabapentinoids gabapentin and pregabalin. The most frequent adverse effects of gabapentin and pregabalin affect the central nervous system, such as somnolence and fatigue. Additionally, pregabalin, and a much lesser extent, gabapentin, may adversely affect the cardiovascular system. Pregabalin induces peripheral edema and may cause or exacerbate heart failure. Pregabalin use has been associated with QTc prolongation in patients taking other QTc–prolonging agents, although the relative contributions of pregabalin to QTc prolongation may be minimal. Pregabalin and gabapentin have been associated with a dose-related increased risk of atrial fibrillation. Most evidence for adverse cardiovascular effects of gabapentinoids derives from case reports and observational studies. Clinicians should be aware of the potential for pregabalin and possibly gabapentin to contribute to cardiovascular dysfunction.

Pregabalin affords retinal neuroprotection in diabetic rats: Suppression of retinal glutamate, microglia cell expression and apoptotic cell death

Pregabalin is the first drug to receive FDA approval for treating diabetic neuropathic pain. This study investigated the neuroprotective effect of pregabalin in an experimental model of diabetic retinopathy and tested some possible mechanisms underlying the putative neuroprotective effect. Male Wistar rats received streptozotocin (45 mg/kg) to induce type 1 diabetes mellitus. After two weeks, a course of pregabalin (3, 10 and 30 mg/kg) has been launched for five consecutive weeks. Retinal expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was estimated by real-time PCR and retinal glutamate content was also estimated. Further, retinal caspase-3 immunoblotting and DNA fragmentation assays determined the degree of apoptosis. Pregabalin improved histopathological abnormalities in diabetic retinas and suppressed the diabetes-enhanced retinal expression of IL-1β, TNF-α, CD11b (a surface marker for microglia) while attenuated expression of caspase-3 and DNA fragmentation versus the diabetic group. In addition, diabetic rats treated with pregabalin displayed reductions in retinal glutamate, nitric oxide and malondialdehyde (MDA) and enhanced reduced glutathione (GSH) content versus the diabetic controls. Furthermore, pregabalin enhanced the histopathological picture and reduced fibrosis in the optic nerve of diabetic rats in addition to suppression of the content of the glia fibrillary acidic protein. The findings provide the first evidence demonstrating that pregabalin alleviates retinal neuroinflammation, apoptosis and oxidative stress in an experimental type 1 diabetes mellitus. Therefore, pregabalin might serve as a potential therapy for retinopathy after adequate clinical research.

The Involvement of GLT‐1 in The Drug Seeking Like Effects of Pregabalin

Pregabalin is a GABA analogue that can bind with high affinity to voltage‐gated calcium channel to minimize excitatory neurotransmitters release. However, several case reports in Middle East and other parts of the world raised the concern of its abuse potential. We have shown in our previous studies that higher doses of pregabalin can cause drug seeking like effect in conditioned place preference (CPP) mouse model. In this study, we tested the involvement of glutamate transporter 1 (GLT‐1), which has a significant role in glutamate homeostasis and in mediating the rewarding and drug seeking effects of several drugs of abuse. Male BALB/c mice were randomly separated into four groups; the control group (C‐C) received saline in home cages and during the conditioning training. The second group (CEF‐C) received ceftriaxone (CEF) in a dose that was consistently shown to upregulate GLT‐1, (200 mg/kg, i.p.), in home cages and received saline during conditioning training. The third group (C‐Preg) received saline in home cages and were administered pregabalin in a dose that previously shown to induce CPP (60 mg/kg) during conditioning training. The last group (CEF‐Preg) received CEF in home cages and injections of pregabalin during the conditioning training. Consistent with our previous studies, the time spent in drug‐paired chamber as compared to the vehicle‐paired chamber was significantly increased in C‐Preg group. Importantly, CEF treatment for eight days blocked pregabalin induced CPP. These results showed for the first time the possible involvement of GLT‐1 in mediating the rewarding effects of pregablin in animal model of drug addiction.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Systematic Review of the Efficacy and Safety of Gabapentin and Pregabalin for Pain in Children and Adolescents.

The barriers to opioid use in some countries necessitate the need to identify suitable alternatives or adjuncts for pain relief. The gabapentinoids (gabapentin and pregabalin) are approved for the management of persistent pain in adults, but not in children. Searches were conducted in Embase, Medline, Scopus, and Web of Science up until November 2017, for randomized controlled trials that investigated the analgesic effects of gabapentin or pregabalin in children and adolescents <18 years of age. A total of 7 publications were identified, 5 regarding gabapentin as prophylactic postsurgical pain relief for either adenotonsillectomy (n = 3) or scoliosis surgery (n = 2), and 1 for gabapentin treatment of chronic regional pain syndrome/neuropathic pain. One study investigated the efficacy of pregabalin as a treatment for fibromyalgia. Based on the studies' primary outcomes alone, neither of the chronic pain studies involving gabapentin and pregabalin showed significant efficacy compared with amitriptyline or placebo, respectively. Two of the prophylactic gabapentin studies for adenotonsillectomy and idiopathic scoliosis surgery reported significantly fewer children requiring analgesia and lower opioid requirement, respectively, compared with placebo. Two of the identified clinical trials (conducted by the same first author) on the efficacy of gabapentin for prophylactic postadenotonsillectomy pain relief were omitted from narrative synthesis due to clear evidence of fabricated data. Overall, this review identified a paucity of evidence for the analgesic effect and safety of gabapentinoids in children. We also suggest audit of any current evidence-based practice and clinical guidelines that have cited the research studies with fabricated data.

Therapeutic effect of pregabalin on radiotherapy-induced trismus in nasopharyngeal carcinoma patients

AimsTo evaluate the effect of pregabalin on radiotherapy-induced trismus in patients with nasopharyngeal carcinoma, a hospital-based, clinical retrospective cohort study was conducted. Materials and methodsData were collected on patients diagnosed with radiotherapy-induced trismus from March 2014 and March 2016 in the department of neurology in our hospital. Patients in the treatment group were administrated pregabalin for 8 weeks combined with rehabilitation, while the control group only received rehabilitation. The clinical therapeutic effects were observed and evaluated by mandibular motion, severity of trismus measured by late effects of normal tissues/subjective and objective medical analysis (LENT/SOMA) scales, and quality of life (QOL) assessed using the World Health Organization QOL instrument (WHOQOL-BREF) at baseline, week 4 and week 8 during treatment in these two groups, respectively. ResultsIn the treatment group, the number of patients with improvement on maximal vertical dimension (MVD) was significantly more than controls at week 4 and week 8 (P=0.013, P=0.004, respectively). Moreover, at week 4 and week 8, the severity of trismus was both significantly improved on LENT/SOMA grade in treatment group (P=0.047, P=0.032, respectively). And at week 8, the physical health and the whole life domain of the WHOQOL-BREF score were significantly increased (P=0.037, P=0.034, respectively). In the treatment group, 11 patients (36.7%) presented dizziness, and 7 patients (23.3%) presented somnolence. ConclusionsAdministration of pregabalin, in adjunct to rehabilitation, might provide a better outcome in patients with radiotherapy-induced trismus.

Pharmacological Prevention of Postoperative Delirium: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background The high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of delirium has become the focus of discussion in recent years. However, a consensus in this respect has yet to be reached. Methods Randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, ClinicalTrials.gov, and Embase databases from their inception through October 12, 2018. We included RCTs of pharmacological prevention for postoperative delirium in adults (at least 18 years), and the Cochrane risk of bias tool was used to evaluate the methodological quality of trials. The primary outcomes were the risk ratios (RRs) of incidence of postoperative delirium, and the secondary outcomes were the RRs of mortality and adverse events in the intervention and control groups. Results Thirty-eight trials, which comprised 20302 patients and 18 different drugs, were included in the analysis. Of the 38 studies, 17 were rated as low risk with respect to methodological quality. Dexmedetomidine administration (RR 0.58, 95%CI 0.44-0.76, P<0.01) was associated with a significantly lower incidence of postoperative delirium than the control conditions. However, the findings from the studies with a low risk of bias did not show a significant difference in this beneficial effect (RR 0.64, 95%CI 0.39-1.04, P=0.07). The antipsychotic drugs olanzapine (RR 0.44, 95%CI 0.30- 0.65, P<0.01) and risperidone (RR 0.42, 95%CI 0.19-0.92, P=0.03) had promising effects, but there was a lack of sufficient evidence to obtain a definitive conclusion. The beneficial effect of other drugs, including haloperidol, methylprednisolone, dexamethasone, gabapentin, ketamine, cyproheptadine, donepezil, hypertonic saline, melatonin, nimodipine, ondansetron, pregabalin, rivastigmine, TJ-54, and tryptophan, was not proven on the basis of present evidence. Conclusion Among the pharmacological prophylactic measures for postoperative delirium, dexmedetomidine, olanzapine, and risperidone showed higher efficacy than other drugs. However, more high-quality evidence is needed to confirm these results.

Perioperative Pregabalin and Intraoperative Lidocaine Infusion to Reduce Persistent Neuropathic Pain After Breast Cancer Surgery: A Multicenter, Factorial, Randomized, Controlled Pilot Trial

Persistent postsurgical pain is defined as pain localized to the area of surgery of a duration of ≥2 months and is, unfortunately, a common complication after breast cancer surgery. Although there is insufficient evidence to support any preventative strategy, prior literature suggests the possible efficacy of intravenous lidocaine and perioperative pregabalin in preventing persistent pain after surgery. To determine feasibility of conducting a larger definitive trial, we conducted a multicenter 2 × 2 factorial, randomized, placebo-controlled pilot trial of 100 female patients undergoing breast cancer surgery. Patients were randomized to receive an intraoperative lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) or placebo and perioperative pregabalin (300 mg preoperatively, 75 mg twice daily for 9 days) or placebo. All feasibility criteria were surpassed; recruitment of 100 patients was accomplished within 42 weeks, with a follow-up rate of 100% and study drug compliance of ≥80%. At 3 months, 53% of patients reported persistent neuropathic pain. Although there was no interaction between lidocaine and pregabalin, lidocaine decreased the development of persistent neuropathic pain (43.1% vs 63.3%; relative risk = .68; 95% confidence interval = .47–1.0). Pregabalin did not reduce persistent pain (60% vs 46%; relative risk = 1.3; 95% confidence interval = .90–1.90) and neither pregabalin nor lidocaine impacted acute postoperative pain, opioid consumption, pain interference, or quality of life. Our pilot trial successfully demonstrated feasibility and provided promising data for conducting further trials of intraoperative lidocaine infusions during breast cancer surgeries.Clinical trial number: NCT02240199 PerspectiveThis article reports the findings of a pilot randomized, controlled trial evaluating the effects of perioperative pregabalin and intraoperative lidocaine infusions in patients undergoing breast cancer surgery. This trial demonstrated the feasibility of conducting a larger trial and provided promising data that these interventions may decrease the development of persistent pain.

Blocking α2δ-1 Subunit Reduces Bladder Hypersensitivity and Inflammation in a Cystitis Mouse Model by Decreasing NF-kB Pathway Activation.

Bladder pain is frequently associated with bladder inflammation, as in conditions like interstitial cystitis (IC), for which current analgesic therapies have limited efficacy. The antinociceptive effect of alpha-2-delta (α2δ) ligands on inflammation-associated visceral pain like that experienced in cystitis has been poorly investigated. To investigate the effect of pregabalin (PGB), an α2δ ligand, we evaluated its impact on mechanical hyperalgesia in a mouse model of cystitis induced by cyclophosphamide (CYP). We further studied its effect on inflammation and NF-kB pathway activation. Acute cystitis was induced by intraperitoneal injection of 150 mg kg-1 of CYP in C57Bl/6J male mice. PGB was subcutaneously injected (30 mg kg-1) 3 h after CYP injection. The effect of PGB on CYP-induced mechanical referred hyperalgesia (abdominal Von Frey test), inflammation (organ weight, cytokine production, α2δ subunit level, NF-kB pathway activation) were assessed 1 h after its injection. In parallel, its effect on cytokine production, α2δ subunit level and NF-kB pathway activation was assessed in vitro on peritoneal exudate cells (PECs) stimulated with LPS. PGB treatment decreased mechanical referred hyperalgesia. Interestingly, it had an anti-inflammatory effect in the cystitis model by reducing pro-inflammatory cytokine production. PGB also inhibited NF-kB pathway activation in the cystitis model and in macrophages stimulated with LPS, in which it blocked the increase in intracellular calcium. This study shows the efficacy of PGB in hypersensitivity and inflammation associated with cystitis. It is therefore of great interest in assessing the benefit of α2δ ligands in patients suffering from cystitis.

Study to determine the effect of oral pregabalin premedication on haemodynamic response to laryngoscopy, intubation and carbon dioxide insufflation during laparoscopic cholecystectomy

Background: The process of laryngoscopy and endotracheal intubation is usually associated with exaggerated haemodynamic response. In extreme cases this response may result in myocardial ischaemia, cardiac failure, increase in intracranial pressure and intracranial haemorrhage. Hence our prospective randomized double blinded placebo control study was designed to observe the effect of pregabalin in attenuating this haemodynamic response. Method: In this study, 100 adult patients of ASAPS I and II undergoing elective laparoscopic cholecystectomy were included. The patients were randomly allocated into two groups, group P received 150mg oral pregabalin and group C received similarly looking B complex capsules one hour before the surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were observed. Sedation score was assessed using Ramsay sedation scale. Results: We observed an increase in all the haemodynamic parameters in both the groups. The percentage change in HR and MAP from baseline at one-minute following intubation was +33% and +28.5% in control group compared to +14% and +3% in pregabalin group. Similarly, the percentage change at five minutes after carboperitoneum was +24% and +26% in control group compared to +4% and +0.8% in pregabalin group. This difference was statistically significant with P value Conclusion: Oral pregabalin in a dose of 150mg one hour before the surgery is a safe and effective premedicant in attenuating pressor response to laryngoscopy, intubation and laparoscopy. It also produces good sedation without any adverse effects.