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Is it safe to take 2 neurabol capsules per day for bodybuilding?

Thanks for the a2a.No it isn't. This is an anabolic steroid called Stanozolol (Winstrol). There used to be a misconception that because it had weak anabolic and androgenic effect (making it useful only in a cutting phase, not for building mass), that it was less toxic. Unfortunately, the opposite seems to be true.Neurabol is just another brandname of stanozolol. The commonly known brand is Winstrol. Read about the negative effects in the article pasted below.HTHUpdate: Instead of pasting links, I’m pasting the entire article (including references) here. Credits go to Dan Gwartney, MD:Winstrol: Bad News and More Bad NewsWritten by Dan Gwartney, MDWednesday, 06 January 2010In 1988, the sporting world was rocked by the announcement proclaiming that Ben Johnson, a Canadian sprinter who’d just shamed Carl Lewis in the Olympic 100-meter race, tested positive for anabolic steroid use. Johnson, who tested positive for stanozolol, was banned for several years from competition, losing his gold medal and an estimated $8.2 million in endorsements.1 Then, the Steroid Control Act of 1990 was passed and steroids became classified as a controlled substance.Little Potency, Lots of DangerStanozolol, known classically by the trade name Winstrol, is a relatively mild steroid in terms of mass or strength gains, yet is extremely popular, particularly with bodybuilders and performance athletes.2 Winstrol (now sold under a variety of brand names and varying tablet strengths and concentrations) was originally available either as a low-strength tablet of two milligrams or as an aqueous suspension containing 50 milligrams per milliliter (mg/ml). Its use was commonly reserved for pre-competition phases for bodybuilders, as it aided in imparting a hardened appearance. In an audiotape series released in 1995 by the magazine Muscle Media 2000, one speaker suggested that a number of runners, particularly endurance runners, used a comparatively low dose of Winstrol to prevent muscle loss secondary to the catabolism experienced during long-distance training and competitions.Stanozolol is the generic name for the chemical 17-Methyl-5alpha-androstano(3,2-c)pyrazol-17beta-ol, identified as CAS registry number 302-96-5.3 Considered to be a highly anabolic steroid due to its impressive anabolic/androgenic ratio, it’s in fact a very mild steroid in terms of muscle or strength gains. The surprising lack of potency is explained by the fact that stanozolol is a very weak androgen and as an anabolic agent, is less effective than a comparable dose of testosterone.4Despite its relatively low potency, stanozolol is still commonly abused, in part due to its reputation for being a “safe” steroid. While stanozolol does not have the more dramatic or obvious side effects seen with many of the highly androgenic steroids, it’s by no means safe. In fact, the published record of medical reports suggests stanozolol may be one of the most dangerous forms of steroids to use.State of ConfusionThe confusion surrounding stanozolol is understandable as its actions are complex and poorly understood. Stanozolol, based upon the highly androgenic, reduced form of testosterone, DHT, would seemingly be a potent androgen, responsible for increased aggression, hair loss and acne. In fact, stanozolol is a very weak androgen4 and rather than promoting aggression, it’s been found to suppress aggression in animals such that they will not even respond to physical provocation or the presence of a male intruder.5,6 Further, the male sex glands, specifically the seminal vesicles, do not respond to stanozolol as a testosterone substitute and rats maintained on stanozolol lose the ability to ejaculate,6,7 eventually eliminating all sexual behavior.8 A similar response is seen in female rats failing to become sexually receptive under the influence of estrogen.9 Thus, in terms of behavior, stanozolol appears to act more as an anti-androgen, rather than an androgen. If these results are applicable to humans, it would make an athlete less competitive and interfere with normal sexual relations.Complicating the social and psychological effects of stanozolol are the numerous reports demonstrating that stanozolol actively blocks normal brain function in a variety of receptor systems, and may interfere with anti-depressants and anxiety medications.10-12 Many steroid users describe a period of “depression” after completing a cycle of steroids and the findings from these studies suggest stanozolol may be exceptionally problematic for those who are subject to the psychological effects of steroid withdrawal. While stanozolol may be a less likely candidate to cause events described as “roid rage,” it may be a dangerous drug for anyone predisposed to suicide or other psychological trauma.Examined by ScienceReferring back to its chemical structure, as a DHT derivative, stanozolol is a reduced steroid, meaning it’s not a substrate for the enzyme aromatase, which is the enzyme responsible for converting most androgens into estrogens (female hormones). Indeed, few bodybuilders report estrogen-related side effects during or following a stanozolol-only cycle. However, the safety of stanozolol in this regard appears to be overstated; drawing upon an animal study, stanozolol was found to accelerate sexual maturation in female, pre-pubescent mice.13 This effect was prevented when an estrogen blocker was given to the mice prior to the stanozolol treatment. Interestingly, though stanozolol caused early changes in the vaginas of these mice, it was not strong enough at the dose studied to cause complete sexual maturation.While this study is inconclusive, it might suggest that stanozolol may be capable of acting as a partial-agonist for the estrogen receptor, similar to the more familiar Nolvadex (Tamoxifen). Though it may not be a substrate for aromatase, meaning it is resistant to being converted into an estrogenic (female) hormone, stanozolol can modestly stimulate aromatase activity, possibly adding to the potential for other androgens to be converted to estrogens.14Another study, examining the effects of stanozolol on skin cells in a lab, discovered that some of the results produced by stanozolol were unique, not explained by its chemical relationship to testosterone.15 Stanozolol has been shown to increase collagen production,16 as well as certain prostaglandins and enzymes within the skin. Investigating this phenomenon, researchers discovered that in the skin fibroblast (an early, undeveloped skin cell), stanozolol could not be displaced (removed) by nortestosterone (an androgen), dexamethasone (a cortisol derivative) or estradiol (an estrogen). Rather, it was partially displaced by progesterone, another female hormone.15 Again, it was interesting to note that though progesterone could displace stanozolol from receptors in the skin cells, progesterone failed to cause the same response. The actions of stanozolol are unclear from this study. It may be possible that stanozolol is capable of interacting with many different receptors, either interfering with other hormones or acting as a weak substitute.None of these studies directly implicate stanozolol as an estrogenic or feminizing compound, and most users’ experiences with stanozolol would confirm that it is non-estrogenic, leading to a hardened appearance with minimal water retention and few reports of gynecomastia. However, the effect of stanozolol, when combined with other agents, may not be as worry free.Liver ToxicityStanozolol is provided in both oral and injectable forms. The chemical is identical in both preparations, the practical difference being that the injectable suspension allows for a higher concentration, usually at a lower cost.2 Stanozolol may be taken orally due to the presence of a methyl group (a small side chain) added to the steroid structure. This addition of the methyl group makes stanozolol one of the 17-alkylated steroids, which are commonly known for being more toxic to the liver than the injectable steroid esters.The liver toxicity of stanozolol is often understated, with most users believing stanozolol is among the least toxic of steroids. In fact, the exact opposite may be closer to the truth. Oral stanozolol has been used for many years in the treatment of a variety of medical conditions, and new uses are being investigated.17-28 Even under conditions in which the drug is prescribed by a physician, dispensed from a legitimate pharmacy, and taken as directed, serious liver damage can occur. In some of the long-term studies reported, half or more of the subjects needed to have the dose lowered or even discontinue treatment due to elevations of the liver enzymes, a sign of cellular damage.22,26 However, most studies concluded that in nearly all cases, the signs and symptoms of liver damage went away with proper intervention and that stanozolol was felt to be a safe treatment alternative for certain conditions.18-20,22,25,27,28The damaging effect of stanozolol upon the liver appears to be very common, and is of greater severity at higher doses. A binding protein has been discovered in rat and human liver specific for stanozolol and danazol, another steroid.29 Studies have proven stanozolol to be hepatotoxic (damaging to the liver).30-32 The effect of an extremely high level of stanozolol (400 times the recommended dose) upon liver cells failed to show any evidence of stanozolol causing or promoting cancer in those cells, even when exposed to other known carcinogens.33 This does not mean, however, that stanozolol is protective against cancer or risk-free, as these results would have to be confirmed and other chemicals may interact with stanozolol in a way that was not evaluated.A case report has been published detailing severe liver damage and acute renal failure in a bodybuilder following the use of stanozolol (i.m. 50 mg every other day) stacked with metandienone (10-50 mg/day) for 80 days.34 This 28-year-old man showed up jaundiced (yellow skin and eyes) three weeks after completing his cycle, and deteriorated for seven weeks until time and treatment allowed him to recover (at significant expense).More Bad NewsThis is not the only reported case of serious health consequences associated with stanozolol. A brief literature search revealed two deaths due to heart attacks,35 two heart attack survivors,36,37 one dangerous cardiac rhythm38 and a life-threatening blood loss,39 all in young men. Few steroids are so commonly associated with serious events such as these, which suggests stanozolol is not yet fully understood.There are a number of other side effects and consequences associated with stanozolol use, but these are well known and generally accepted by the professional and athletic community. Briefly, stanozolol negatively affects the risk of heart attack or stroke by lowering the “good cholesterol” and raising the “bad cholesterol.”25,40,41 Women may experience masculinizing effects even at very low doses (2 mg/day).2,22,26,28 Stanozolol also increases the risk of serious bleeding, from the annoyance of nosebleeds to the life-threatening condition known as esophageal varices;23-25,31,39 may make tendons more prone to injury;42,43 is easily detected in hair and urine and remains detectable for several months following discontinuation;44-48 suppresses natural testosterone production;49,50 and dramatically lowers the carrier protein for androgens in the blood, called sex-hormone binding protein (SHBG).51,52SHBG, which protects androgens from being metabolized and cleared from the body, is decreased by 50 percent with three days’ use of a low dose of stanozolol.51,52 At first glance, this may appear to be a positive effect, making what androgens are injected or swallowed less likely to be “bound” (prevented from stimulating muscle growth), instead allowing the steroid to float in the bloodstream as a “free” steroid, whereby it can interact with the muscle cell and cause hypertrophy. This is not such a benefit in the body, as SHBG protects androgens from rapid degradation and allows for the effect of testosterone or other androgens to persist for a longer period. SHBG lowers as a defense mechanism, allowing the body to shed excess androgens more quickly.Summing UpIn conclusion, stanozolol, generally known as Winstrol, is a commonly abused steroid that’s felt by many users to be a very mild and safe anabolic. Though stanozolol doesn’t carry the risk of the more obvious and dramatic androgenic or estrogenic side effects of other drugs, it may be all the more dangerous for its subtle nature. Stanozolol appears to act upon many different systems in the body and brain, affecting many functions beyond androgen-stimulated hypertrophy of the muscle.It’d been shown to mimic the effects of estrogen and shares a binding site with progesterone (female hormones); decreases sexual drive, sexual function and aggression; may cause or interfere with the treatment of psychological disorders; is highly likely to cause liver damage (fortunately this appears to be reversible in most cases); and may be involved with the development of life-threatening or fatal events, including heart attacks and bleeding. It may cause the body to more rapidly clear androgens and is easily detectable for long periods in both hair and urine.Bodybuilders report using doses of 50-100 mg/day,2 yet doses as low as six to 10 mg/day have been shown to increase nitrogen retention greater than 200-300 milligrams of testosterone enanthate/week.53 This low dose has been used safely in studies monitored by physicians, though more than half of users, even at this low dose, need to have the dose lowered or discontinued due to liver damage or other side effects. Given that there are other steroids with fewer known risks, and that stanozolol is comparatively weak as both an androgen and an anabolic steroid, greater caution should be used by those considering stanozolol.References1. Benjamin D. Shame of the Games. Available through Time Magazine online, http://www.time.com/time/daily/newsfiles/olympics/summer88/johnson.html accessed June 28, 2002.2. Llewellyn W. Anabolics 2002. Molecular Nutrition Press, Patchogue NY, 2002 pp 177-80.3. ChemIDPlus. Provided through the National Library of Medicine. Available at Chemical information with searchable synonyms, structures, and formulas accessed June 28, 2002.4. Saartok T, Dahlberg E, et al. Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin. Endocrinology 1984 Jun;114(6):2100-6.5. McGinnis MY, Lumia AR, et al. Physical provocation potentiates aggression in male rats receiving anabolic androgenic steroids. Horm Behav 2002 Feb;41(1):101-10.6. Clark AS, Barber DM. Anabolic-androgenic steroids and aggression in castrated male rats. Physiol Behav 1994 Nov;56(5):1107-13.7. Clark AS, Harrold EV. Comparison of the effects of stanozolol, oxymetholone, and testosterone cypionate on the sexual behavior of castrated male rats. Behav Neurosci 1997 Dec;111(6):1368-74.8. Clark AS, Harrold EV, et al. Anabolic-androgenic steroid effects on the sexual behavior of intact male rats. Horm Behav 1997 Feb;31(1):35-46.9. Blasberg ME, Clark AS. Anabolic-androgenic steroid effects on sexual receptivity in ovariectomized rats. Horm Behav 1997 Dec;32(3):201-8.10. Masonis AE, McCarthy MP. Direct interactions of the androgenic/anabolic steroids with the peripheral benzodiazepine receptor in rat brain: implications for the psychological and physiological manifestations of androgenic/anabolic steroid abuse. J Steroid Biochem Mol Biol 1996 Aug;58(5-6):551-5.11. Masonis AE, McCarthy MP. Effects of the androgenic/anabolic steroid stanozolol on GABAA receptor function: GABA-stimulated 36Cl-influx and [35S] TBPS binding. J Pharmacol Exp Ther 1996 Oct;279(1):186-93.12. Masonis AE, McCarthy MP. Direct effects of the anabolic/androgenic steroids, stanozolol and 17 alpha-methyltestosterone, on benzodiazepine binding to the gamma-aminobutyric acid(a) receptor. Neurosci Lett 1995 Apr 7;189(1):35-8.13. Whitney AC, Clark AS. Effects of acute stanozolol treatment on puberty in female rats. Biol Reprod 2001 May;64(5):1460-5.14. Roselli CE. The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area. Brain Res 1998 May 11;792(2):271-6.15. Ellis AJ, Cawston TE, et al. The differential effects of stanozolol on human skin and synovial fibroblasts in vitro: DNA synthesis and receptor binding. Agents Actions 1994 Mar;41(1-2):37-43.16. Falanga V, Greenberg AS, et al. Stimulation of collagen synthesis by the anabolic steroid stanozolol. J Invest Dermatol 1998 Dec;111(6):1193-7.17. Revenga F, Aguilar C, et al. Cryofibrinogenaemia with a good response to stanozolol. Clin Exp Dermatol 2000 Nov;25(8):621-3.18. Parsad D, Pandhi R, et al. Stanozolol in chronic urticaria. J Dermatol 2001 Jun;28(6):299-302.19. Helfman T, Falanga V. Stanozolol as a novel therapeutic agent in dermatology. J Am Acad Dermatol 1995 Aug;33(2 Pt 1):254-8.20. Daniel F, Rao DG, et al. A pilot study of stanozolol for advanced breast carcinoma. Cancer 1991 Jun 15;67(12):2966-8.21. Cooper RG, Mitchell WS, et al. Fibrinolytic enhancement with stanozolol fails to improve symptoms and signs in patients with post-surgical back pain. Scand J Rheumatol 1991;20(6):414-8.22. Sheffer AL, Fearon DT, et al. Hereditary angioedema: a decade of management with stanozolol. J Allergy Clin Immunol 1987 Dec;80(6):855-60.23. Broekmans AW, Conard J, et al. Treatment of hereditary protein C deficiency with stanozolol. Thromb Haemost 1987 Feb 3;57(1):20-4.24. Belch JJ, Madhok R, et al. The effect of increasing fibrinolysis in patients with rheumatoid arthritis: a double blind study of stanozolol. Q J Med 1986 Jan;58(225):19-27.25. Kluft C, Preston FE, et al. Stanozolol-induced changes in fibrinolysis and coagulation in healthy adults. Thromb Haemost 1984 Apr 30;51(2):157-64.26. Chesnut CH, Ivey JL, et al. Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action. Metabolism 1983 Jun;32(6):571-80.27. Cicardi M, Bergamaschini L, et al. Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives. J Allergy Clin Immunol 1983 Sep;72(3):294-8.28. Cicardi M, Bergamaschini L, et al. Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience. J Allergy Clin Immunol 1991 Apr;87(4):768-73.29. Luzardo OP, Machin RP, et al. Photoaffinity labeling identification of a specific binding protein for the anabolic steroids stanozolol and danazol: an oligomeric protein regulated by age, pituitary hormones, and ethyl estradiol. Endocrinology 2000 Sep;141(9):3377-87.30. Boada LD, Zumbado M, et al. Evaluation of acute and chronic hepatotoxic effects exerted by anabolic-androgenic steroid stanozolol in adult male rats. Arch Toxicol 1999 Nov;73(8-9):465-72.31. Harkin KR, Cowan LA, et al. Hepatotoxicity of stanozolol in cats. J Am Vet Med Assoc 2000 Sep 1;217(5):681-4.32. Welder AA, Robertson JW, et al. Toxic effects of anabolic-androgenic steroids in primary rat hepatic cell cultures. J Pharmacol Toxicol Methods 1995 Aug;33(4):187-95.33. Ghia M, Mereto E. Assay of stanozolol for tumor initiating and promoting activity in two rat liver foci bioassays. Cancer Lett 1992 Apr 30;63(3):203-9.34. Habscheid W, Abele U, et al. Severe cholestasis with kidney failure from anabolic steroids in a bodybuilder. Dtsch Med Wochenschr 1999 Sep 10;124(36):1029-32.35. Fineschi V, Baroldi G, et al. Anabolic steroid abuse and cardiac sudden death: a pathologic study. Arch Pathol Lab Med 2001 Feb;125(2):253-5.36. Mewis C, Spyridopoulos I, et al. Manifestations of severe coronary heart diease after anabolic drug abuse. Clin Cardiol 1996 Feb;19(2):153-5.37. Goldstein DR, Dobbs T, et al. Clenbuterol and anabolic steroids: a previously unreported cause of myocardial infarction with normal coronary angiograms. South Med J 1998 Aug;91(8):780-4.38. Sullivan ML, Martinez CM, et al. Atrial fibrillation and steroids. J Emer Med 1999 Sep-Oct;17(5):851-7.39. Winwood PJ, Robertson DA, et al. Bleeding oesophageal varices associated with anabolic steroid use in an athlete. Postgrad Med J 1990 Oct;66(780):864-5.40. Thompson PD, Cullinane EM, et al. Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA 1989 Feb 24;261(8):1165-8.41. Bausserman LL, Saratelli AL, et al. Effects of short-term stanozolol administration on serum lipoproteins in hepatic lipase deficiency. Metabolism 1997 Sep;46(9):992-6.42. Inhofe PD, Grana WA, et al. The effects of anabolic steroids on rat tendon. An ultrastructural, biomechanical, and biochemical analysis. Am J Sports Med 1995 Mar-Apr;23(2):227-32.43. Miles JW, Grana WA, et al. The effect of anabolic steroids on the biomechanical and histological properties of rat tendon. J Bone Joint Surg Am 1992 Mar;74(3):411-22.44. Cirimele V, Kintz P, et al. Testing of anabolic stanozolol in human hair by gas chromatography-negative ion chemical ionization mass spectrometry. J Chromatogr B Biomed Sci Appl 2000 Apr 14;740(2):265-71.45. Schanzer W, Opfermann G, et al. Metabolism of stanozolol: identification and synthesis of urinary metabolites. J Steroid Biochem 1990 Jun;36(1-2)):153-74.46. Choo HY, Kwon OS, et al. Quantitative determination of stanozolol and its metabolite in urine by gas chromatography/mass spectrometry. J Anal Toxicol 1990 Mar-Apr;14(2):109-12.47. Schanzer W, Delahaut P, et al. Long-term detection and identification of metandienone and stanozolol abuse in athletes by gas chromatography-high-resolution mass spectrometry. J Chromatogr B Biomed Appl 1996 Dec 6;687(1):93-108.48. Dumestre-Toulet V, Cirimele V, et al. Hair analysis of seven bodybuilders for anabolic steroids, ephedrine, and clenbuterol [In Process Citation] J Forensic Sci 2002 Jan;47(1):211-4.49. Ballarin E, Guglielmini C, et al. Unmodified performance in runners following anabolic steroid administration. Int J Sports Med 1986 Dec;7(6):302-6.50. Small M, Beastall GH, et al. Alteration of hormone levels in mormal males given the anabolic steroid stanozolol. Clin Endocrinol (Oxf) 1984 Jul;21(1):49-55.51. Sinnecker GH, Hiort O, et al. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur J Pediatr 1997 Jan;156(1):7-14.52. Sinnecker G, Kohler S. Sex hormone-binding globulin response to the anabolic steroid stanozolol: evidence for its suitability as a biological androgen sensitivity test. J Clin Endocrinol Metab 1989 Jun;68(6):1195-200.53. Fryburg DA, Weltman A, et al. Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men: impact of gonadal steroid and GH secretory changes on metabolic outcomes. J Clin Endocrinol Metab 1997 Nov;82(11):3710-9.

Why is my knee still stiff a year after a total knee replacement?

ABSTRACT:Objective:To study and understand the side effects, efficiency and outcomes of Gabapentin, Intravenous Lidocaine and their combination for the reduction of postoperative pain after the total knee replacement.Study design:After understanding the objective, a case-control study was done and all the side effects, as well as benefits, were observed after ensuring the safety of all the patients.Place and Duration of study:The study was performed in Tertiary Care Hospital and the duration for the study was six months.Methodology:Sixty-six patients were included in the study. Group A, B and C were given Gabapentin, lidocaine and their combination respectively. For the data analysis procedure, Statistical Package for Social Science Software of version 22 was used. Chi-square test was used to collect categorical data and p-value less than 0.05 was considered significant.Results:Age, weight, gender and duration of surgery were some factors that did not differ significantly in all groups. Relief of pain was observed in all three groups within 24 hours. Blurred vision, uncontrolled eye movement and dizziness were observed in patients of group B. Whereas in Group A, vomiting and change of body temperature were observed.Conclusion:To reduce the postoperative pain by analgesic effect, intravenous lidocaine as well as Gabapentin, both are effective, safe and significant but have some side effects too. Also, their combination reduces the pain, but the side effects are decreased by its use. For overcoming postoperative nausea and vomiting, Gabapentin is the most suitable drug.Keywords: anaesthesia, Gabapentin, intravenous lidocaine, postoperative pain, surgerytotal knee replacementINTRODUCTION:End-stage Osteoarthritis, rheumatic arthritis, trauma, and other joint disorders can cause severe pain, restrict mobility and physical inactiveness. These joint destructive disorders are usually common in older and mid-aged adults. Inflammation of the synovial membrane and damage to knee cartilage are some of the consequences of these disorders. To have a pain-free life and increased mobility, total knee replacement, also known as total knee arthroplasty is recommended in these severe conditions (1)(2).In the United States, osteoarthritis is the major cause of total knee replacement. The damaged cartilage and the bone are removed from that point where femur and tibia meet on the knee joint. Then these damaged parts of the knee joint are replaced by metal and plastic artificial parts in the surgery so that, you can move and bend your knee without any pain. Postoperative pain is usually associated with this procedure. 60% of the patients experience chronic pain whereas 30% face moderate pain. Not all the patients have the courage to have this surgery, because of the fear of postoperative pain. Moreover, thromboembolism risk and early ambulation are consequences of postoperative pain. So, the need for the management of postoperative pain after the knee replacement is obvious (3)(4).Opioid analgesics are mostly used to reduce the postoperative pain, but they are also associated with high morbidity rate and hospital costs. Not only this, but it also comes with some severe side effects including development of tolerance, constipation, pruritus and respiratory depression. Several analgesics and anaesthetic medications are used to overcome the pain. But, every medicine, along with its benefits, has some side effects (5). In this research, we will discuss two medicines, Gabapentin and Intravenous Lidocaine, their efficiency and side effects as a treatment for the postoperative pain.Gabapentin (1-aminomethyl cyclohexane acetic acid) is an anticonvulsant drug that is usually used to treat migraine and other several neuropathic pain syndromes (6)(7). It is associated with alpha 2-delta subunit of voltage-gated calcium channels. Some of the recent studies have proved that Gabapentin can be used as an analgesic agent for postoperative pain after the total knee replacement. It is not an analgesic drug, but the opioid requirement can be decreased by its use as well as it can improve analgesia. This non-epileptic drug has central and peripheral antalgic activity (6). Some research has shown that Gabapentin shows its effect within 24 hours of the surgery and also preoperative anxiety, postoperative nausea, vomiting, and pruritus can be treated by its use. Fatigue, dizziness, uncoordinated movement, tiredness, blurred vision, uncontrolled or repetitive eye movements and tremor can be some of the side effects of Gabapentin (8) (7). Another side effect on the drug is sleepiness but this side effect can be considered beneficial because it can soothe the patient and provide them with some rest after the surgery. This route of administration for this medication is oral.Lidocaine is an anaesthetic drug, also known as lignocaine, that is used to numb a specific area of the body to reduce the pain (9)(10). The chemical formula of the drug is 2-(Diethylamino)-N-(2,6-dimethyl phenyl) acetamide. In 1943, the medication was first used for pain as a result of a burn. peripheral nociceptors sensitization and central hyperexcitability, both the activities are supported by lidocaine. It can also play a role as an anti-inflammatory and anti-hyper analgesic drug. Intravenous lidocaine has some benefits that the other local anaesthetics lack including the perioperative infusion. It has been observed that postoperative pain is reduced after the introduction of lidocaine in the dorsum of the foot. The half-life of the drug is increased by more than 5.5 times after it is introduced. Other benefits include a lesser opioid requirement, first flatus in a very short time, reduce hospital stay and decrease nausea. Whereas the common side effects are dizziness, vomiting, feeling hot or cold, confusion, ringing in your ears and blurred vision. Apart from the separate use of these two drugs, some studies have analysed that the combination of both the drugs can give the best results and reduce the pain after the surgery. (11)(12).The time duration during which the Gabapentin's peak plasma level is obtained is 2-3 hours after its intake. Metabolism does not occur and it is removed from the body in some form, from the urine. Multiple types of research have been done and the results showed that dose of Gabapentin, surgery nature and administration, all factors are not the same for every patient. Ho et al. performed a study in which the dose of Gabapentin used was 1200 mg before the surgery. This was done to make sure that the consumption of opioid should be minimized after the surgery (13). Sedation was an expected side effect of this procedure but the patients did not have to face the side effects of opioid consumption. (14) Pandey et al. made a review in which he kept on rising the dose from 600mg to 1200mg. The increased dosage did not lessen the postoperative pain hence, 600 mg was considered as the ideal dosage (15). Another study performed to reduce the postoperative pain after total knee replacement showed that 300mg of Gabapentin given 90 hours before the surgery to the patients will show significant results. Farag et al. had a study in which IV lidocaine was given to the patients having spin surgery. The postoperative pain was reduced (P < 0.001. almost, 25% of the opioid consumption was also reduced in the study so, we can correlate this one with the present study (16).In some other researches, it has shown that intravenous lidocaine is not significant in treating postoperative pain. Also, the opioid consumption was not reduced in any kind of surgery by its use. Martin et al. performed a surgery that included the patients having total hip arthroplasty. The lidocaine bolus was given to the patients and no significant effect was noticed about pain score or opioid consumption(17)(18).Another study performed by De Oliveira and co-authors showed that if the patients of two groups, one has given IV lidocaine and other have given saline, no effect was noticed regarding pain as well as morphine consumption(17)(18).In addition to the above-discussed studies, this ineffective result of intravenous lidocaine was also observed in some other research. The mismatch between the results of the current study and these previous studies is due to the varying amount of dosage and different nature of surgeries. Also, we can say that the difference is due to the unique pain thresholds of a particular individual. So, each of them has a different response to each drug(19).So, according to the above-discussed literature, both the methods have some better results as well as bad side effects. We will study the significant effect of oral Gabapentin and intravenous lidocaine in patients undergoing total knee replacement. So, the side effects and results of both the drugs and their combined effects are observed in the study to understand the best way to overcome the postoperative pain after total knee replacement.METHODOLOGY:It was a case-control study performed at Tertiary Care Hospital and the duration of the study was 6 months. 66 patients that were suffering from any kind of arthritis or knee joint disorder were selected for the study. Ethical statement of the patient was the priority and written consent was also taken from every patient as a record. The whole procedure was explained to all patients and the choice of with-drawl at any time was provided as well. The inclusion criteria for the study included patients of age more than 18 years, both male and female gender, patients undergoing surgery with general anaesthesia and mainly the patients that were suffering from any kind of arthritis or knee joint disorder. Whereas the exclusion criteria included patients with neoplastic aetiology, infection, traumatic fracture, metal sensitivity, obstructive sleep apnea, revision surgery, mental diseases, and use of the local anaesthetic technique or a nerve block. Three groups were made and named as A, B and C. Patients were divided equally so that each group consists of 22 patients.Before the study, the whole procedure will be explained to the patients. All the steps will be performed after taking consent from them in a written form. Every minor detail including the delicacies, benefits, risks and complaints of the procedure will be made clear. No one will be forced to take part in the study. The Hospital ethical committee should also have approved the study.The patients of A group were given placebo capsules 1 hour before the surgery. Then, just before giving anaesthesia, IV bolus injection of 1.0 mg/kg lidocaine (Xylocaine 2%; AstraZeneca, 600 Capability Green, Luton, LU1 3LU, UK) was introduced to the patients. The solution was diluted by normal saline to a 10 ml volume. Then, it was infused continuously, until the skin was closed. A syringe was pumped at the rate of 2 mg/kg/h during surgery. In group B, 1 hour before the surgery, patients were given 600 mg gabapentin capsules (Neurontin; Pfizer, Cairo, Egypt). They were allowed to ingest the capsule. Then, before giving anaesthesia the patients were given 10 ml of the saline bolus. After that saline infusion was done intraoperatively (the same volume as lidocaine infusion in group A). The same syringe pump was used for the procedure until the closure of skin. Whereas in group c, patients were allowed to ingest 600 mg gabapentin capsules. Similar to group A and B, it was done 1 hour before surgery. Then, just before having anaesthesia, they received IV bolus of 1.0 mg/kg lidocaine. After that, the same syringe pump was used in this procedure for intraoperative lidocaine infusion. Before the closure of skin, the process was done at the rate of 2 mg/kg/h. there was no specific dose for the administration of IV drug. The amount to be given was calculated according to the weight of the patient. All the persons involved in the research including the surgeons, patients as well as anaesthesiologists did not know the allocation of the groups. So, they could deduce the result without any doubts. Preoperative condition of the patients including their assessment was done 24 hours before the surgery. The patients were explained how to express the intensity of pain ranging from 10-10 by using the visual analogue score (VAS; 0 = no pain and 10 = worst pain imaginable) (20).DATA ANALYSIS:For data analysis procedure, SPSS software (Statistical Package for the Social Science; SPSS Inc, Chicago, IL, USA) was used with version 22. In statistical analysis, data were explained as mean ± standard deviation (±SD), or frequencies (number of cases) and percentages when appropriate. All of the three groups were evaluated and the results were compared by one-way analysis of variance (ANOVA) test. Mann Whitney U test was used to evaluate the independent samples. Also, Bonferroni correction was used for several evaluations in every group for comparison. Categorical data were compared by using the Chi-square (χ2) test was used to collect categorical data. If the frequency was less than 5, Exact test was used. P-values less than 0.05 was considered significant (21)(22).RESULTS:The study was completed by sixty-six patients that were undergoing total knee replacement surgery by using general anaesthesia. 22 patients were present in each group (n=22 in group A, B and C). Age, weight, gender and duration of surgery were some factors that did not differ significantly in all groups. Relief of pain was observed in all three groups within 24 hours. Blurred vision, uncontrolled eye movement and dizziness were observed in patients of group B. Whereas in Group A, vomiting and change of body temperature were observed. Intra-operative heart rate, postoperative side-effects, and mean arterial pressure changes were also recorded as results.TABLE Ⅰ: Intra-operative heart rate.Time(A) Group(n=22)(B) Group(n=22)(C) Group(n=22)Before induction95.4 ± 12.294.8 ± 12.492.5 ± 11.9After induction99.2 ± 10.898.6 ± 11.696.9 ± 12.6After 15 min94.6 ± 9.893.7 ± 10.292.4 ± 10.3After 30 min95.4 ± 10.994.8 ± 10.793.8 ± 11.7After 45 min93.7 ± 10.294.7 ± 10.692.4 ± 10.2After 60 min92.6 ± 11.893.9 ± 11.792.6 ± 12.1After 75 min93.5 ± 10.593.5 ± 11.491.5 ± 11.6After 90 min92.5 ± 10.193.4 ± 9.692.4 ± 9.2At the end of surgery93.2 ± 10.894.6 ± 12.293.8 ± 12.8TABLE Ⅱ: Changes in mean arterial pressureTime(A) Group(n=22)(B) Group(n=22)(C) Group(n=22)Before induction86.4 ± 16.585.8 ± 16.782.2 ± 15.6After induction90.2 ± 7.890.6 ± 6.789.4 ± 9.5After 15 min87.6 ± 7.886.7 ± 6.986.5 ± 7.1After 30 min87.7 ± 7.988.4 ± 8.287.9 ± 8.4After 45 min86.5 ± 8.287.7 ± 8.485.8 ± 8.8After 60 min86.7 ± 7.489.6 ± 8.285.9 ± 7.9After 75 min91.4 ± 7.890.1 ± 7.990.2 ± 7.8After 90 min88.6 ± 8.287.3 ± 8.489.4 ± 8.6At the end of surgery90.7 ± 8.991.4 ± 8.489.4 ± 8.2TABLE Ⅲ: Post-operative side effectsPostoperative side effects(A) Group(n=22)(B) Group(n=22)(C) Group(n=22)Nausea5 (22.7%)2 (9%)2 (9%)Vomiting4 (18.1%)2 (9%)1 (4.5%)Dizziness4 (18%)6 (27%)7 (31%)Headache4 (18.1%)3 (13.6%)4 (18.1%)Dry mouth4 (18.1%)6 (27.2%)6 (27.2%)TABLE Ⅳ: Demographic Data of PatientsVariables(A) Group(n=22)(B) Group(n=22)(C) Group(n=22)Age (years)46.9 ± 7.745.4 ± 6.747.8 ± 8.2Male/female (n)6/165/177/15ASA class 1 / 2 (n)8/146/168/14Weight (kg)89 ± 8.790.2 ± 8.288.7 ± 8.6Duration of surgery (min)130 ± 28134 ± 29132 ± 28Intraoperative fentanyl227 ± 39.8220 ± 34.2180 ± 30.4Extubation time (min)10.4 ± 1.49.8 ± 1.710.6 ± 1.2DISCUSSION:Pre-operative anxiety is usually a serious issue, but postoperative pain is more a centre of attention here. Both of them are somehow connected as the anxiety leads to decreased pain thresholds as a result of which severe pain is suffered by the patients that have undergone knee surgery. Also, the pain and anxiety have a significant effect on wound healing time as well as the immune system. So, to overcome the pain, analgesics are sued. In this study, we used oral Gabapentin, intravenous lidocaine and their combination.Total knee replacement is major surgery with severe postoperative pain as a complication. To avoid a long-hospital stay, it is mandatory to manage postoperative pain. A method that has been used for 25 years to control the postoperative pain is a multimodal analgesic pathway which decreases the severity of pain. Gabapentin used to overcome this pain has varying effects on the patients. 6 out of 7 studies have reported that opioid use does not play role in releasing the pain in between the 24 hours of the surgery.The result of the present study shows that group C having a combination of Gabapentin and lidocaine shows fewer postoperative complications and side effects than the other two groups. Also, the other two groups A and B, Intravenous Lidocaine and Gabapentin respectively. The intravenous lidocaine was considered significant for improving the postoperative pain at the initial stage. Less pain was detected in the patients on each movement that were given the dose of lidocaine. In addition to it, the requirement of morphine was reduced in this case. Gabapentin was considered to decrease the postoperative pain in the first 24 hours of the surgery. If compared these three groups with placebo, then lidocaine group had no difference in the case of nausea and vomiting. In contrast, the gabapentin group and combined group were more significant than these two. (23)The postoperative sedation was found in all the three groups in the study. The level of sedation was different in the cases if compared to previous studies. In previous studies, the sedation level was higher in the gabapentin group just because of higher or repeated dosages. Other factors of Gabapentin that was compared to other groups were headache and dizziness. So, some research has shown that if the ideal amount of Gabapentin is used, i.e., 600-800mg is consumed, then all the postoperative effects can be overcome. (24)Kaba et al. performed a study in which patients who had laparoscopic colectomy were included. Intravenous lidocaine was given to these patients for the reduction of postoperative pain. His research showed significant results and postoperative pain, along with the need for opioid use was decreased. IV magnesium infusion and placebo infusion were compared to IV lidocaine in another study. The pain was reduced both by lidocaine and magnesium than placebo. The result of these studies supports the results of our research that IV lidocaine can manage postoperative pain (25).Now, there were some limitations to the study. A limitation was that the plasma lidocaine concentration was not measured. Also, the amount of lidocaine given to the patients in a short time was lesser as compared to other studies. These additional studies showed no side effects, and their toxic level was not found. Another limitation of the study is a smaller sample size which has limited the better exposure to the side effects of any group. Either it is gabapentin or IV lidocaine, both were significant in lowering the postoperative pain. Also, they were safe and inexpensive and a better solution as compared to opioid. Not only in knee surgery but different surgeries should also be studied profoundly, and the safe, optimum and effective dosage should be detected for them to reduce the postoperative pain.CONCLUSION:To reduce the postoperative pain by analgesic effect, intravenous lidocaine as well as Gabapentin, both are effective, safe and significant but have some side effects too including nausea, vomiting, headache, dizziness and dry mouth. Also, their combination reduces the pain, but the main point is that its use also decreases the side effects. Whereas, for overcoming postoperative nausea and vomiting, among all three methods, oral Gabapentin is the most suitable drug.REFERENCES:1. M.-L. W, Y.-J. F, C.-J. T, P.-J. Y, Y.-L. L, C.-C. J. Successful management of 73 patients for total knee arthroplasty using a combination of ultrasound-guided nerve block and targeted sedation. Anesth Analg. 2018;2. Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen O, et al. A randomized, controlled trial of total knee replacement. N Engl J Med. 2015;3. Petersen KK, Graven-Nielsen T, Simonsen O, Laursen MB, Arendt-Nielsen L. Preoperative pain mechanisms assessed by cuff algometry are associated with chronic postoperative pain relief after total knee replacement. Pain. 2016;4. Chou R, Gordon DB, De Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of postoperative pain: A clinical practice guideline from the American pain society, the American society of regional anesthesia and pain medicine, and the American society of anesthesiologists’ committee on regional anesthesia, executive commi. J Pain. 2016;5. Lovich-Sapola J, Smith CE, Brandt CP. Postoperative Pain Control. Surgical Clinics of North America. 2015.6. Gomes T, Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W. Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case–control study. PLoS Med. 2017;7. Cooper TE, Derry S, Wiffen PJ, Moore RA. Gabapentin for fibromyalgia pain in adults. Cochrane Database of Systematic Reviews. 2017.8. Evoy KE, Morrison MD, Saklad SR. Abuse and Misuse of Pregabalin and Gabapentin. Drugs. 2017.9. Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;10. Dunn LK, Durieux ME. Perioperative Use of Intravenous Lidocaine. Anesthesiology. 2017.11. Thomazeau J, Rouquette A, Martinez V, Rabuel C, Prince N, Laplanche JL, et al. Acute pain Factors predictive of postoperative pain and opioid requirement in multimodal analgesia following knee replacement. Eur J Pain (United Kingdom). 2016;12. Meissner W, Coluzzi F, Fletcher D, Huygen F, Morlion B, Neugebauer E, et al. Improving the management of postoperative acute pain: Priorities for change. Current Medical Research and Opinion. 2015.13. Cheng GS, Ilfeld BM. An Evidence-Based Review of the Efficacy of Perioperative Analgesic Techniques for Breast Cancer-Related Surgery. Pain medicine (Malden, Mass.). 2017.14. Thiruvenkatarajan V, Wood R, Watts R, Currie J, Wahba M, Van Wijk RM. The intraoperative use of non-opioid adjuvant analgesic agents: A survey of anaesthetists in Australia and New Zealand. BMC Anesthesiology. 2019.15. R. C. The state of the art for evidence-based non-opioid pain management. Am J Addict. 2017;16. Paul JE, Nantha-Aree M, Buckley N, Shahzad U, Cheng J, Thabane L, et al. Randomized controlled trial of Gabapentin as an adjunct to perioperative analgesia in total hip arthroplasty patients. Can J Anesth. 2015;17. Alviar MJM, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database of Systematic Reviews. 2016.18. Euasobhon P, Dej-arkom S, Siriussawakul A, Muangman S, Sriraj W, Pattanittum P, et al. Lidocaine for reducing propofol-induced pain on induction of anaesthesia in adults. Cochrane Database of Systematic Reviews. 2016.19. Estebe JP. Intravenous lidocaine. Best Practice and Research: Clinical Anaesthesiology. 2017.20. Seki H, Ideno S, Ishihara T, Watanabe K, Matsumoto M, Morisaki H. Postoperative pain management in patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis: A narrative review. Scoliosis Spinal Disord. 2018;21. NCT03198871. IV Acetaminophen for Post-Operative Pain Management in Enhanced Recovery After Surgery (ERAS) Population. http://Https://clinicaltrials.gov/show/nct03198871. 2017;22. Drudis R, Colomina J, Torra M, Villalba P, Marco G, Del Pozo D, et al. ESRA19-0442 Adductor canal block in an enhanced recovery program after total knee arthroplasty. In 2019.23. Ventham NT, Kennedy ED, Brady RR, Paterson HM, Speake D, Foo I, et al. Efficacy of Intravenous Lidocaine for Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis. World J Surg. 2015;24. Arai YCP, Hatakeyama N, Nishihara M, Ikeuchi M, Kurisuno M, Ikemoto T. Intravenous lidocaine and magnesium for management of intractable trigeminal neuralgia: A case series of nine patients. J Anesth. 2013;25. Gilron I, Tu D, Dumerton-Shore D, Duggan S, Rooney R, McGrath M, et al. The effect of triple vs. double nonopioid therapy on postoperative pain and functional outcome after abdominal hysterectomy. Eur J Anaesthesiol. 2015;

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