Effects of Body Mass Index on Parasympathetic Nervous System Reactivity and Recovery Following Orthostatic Stress.

Vagally mediated heart rate variability (vmHRV), defined as the beat-to-beat fluctuations in a heart series mediated by the vagus nerve, serves as a non-invasive index of parasympathetic nervous system (PNS) activity. Lower resting state vmHRV is associated with greater body mass index (BMI), providing a psychophysiological pathway linking obesity with health and disease. However little research has been conducted to examine how BMI may influence PNS reactivity to orthostatic stress. The present study sought to explore this in a sample of 59 individuals (44 females, mean age = 24.37 years, age range 19-65 years). VmHRV was measured throughout the 5-minute baseline (sitting), orthostatic (standing), and recovery (sitting) conditions. Individuals were stratified into low (BMI < 20), moderate (BMI 20-25), and high (BMI > 25) BMI groups. Results indicate that the high BMI group had a greater decrease in vmHRV from baseline to standing in comparison to the moderate BMI group. Furthermore, the low BMI group showed lower vmHRV during recovery compared to baseline, suggesting that these individuals did not fully recover from the standing position. Taken together, these results extend previous literature showing that those with low and high BMI can show different yet maladaptive patterns of vmHRV in response to orthostatic stress.

Early postoperative predictors of satisfaction following total knee arthroplasty.

BACKGROUND: Despite the excellent total knee arthroplasty (TKA) results reported using traditional outcome measures, dissatisfaction rates of up to 30% are reported following surgery. Although several preoperative factors have been identified as possible predictors of satisfaction, there is conflicting evidence. Identification of dissatisfaction in the early postoperative assessment may therefore be an alternative consideration. METHODS: We examined the relationship between 12-month satisfaction, and early post-operative outcomes in a cohort of 486 TKA patients. Preoperative, and postoperative outcome measures at 3- and 12-months (Oxford knee score, pain score, SF12, and knee motion), were analysed and compared between patients who were satisfied and dissatisfied at 12-months following TKA. Mean scores, and postoperative change in scores were calculated. Postoperative outcomes were examined for correlation with satisfaction, and multivariate logistic regression models used to identify potential predictors of dissatisfaction. RESULTS: Overall satisfaction was 77.0%. No preoperative differences were observed between groups. Dissatisfaction was associated with worse postoperative status across all outcome measures (p<0.001), except the 3-month SF12-physical component (p=0.052). Dissatisfied patients demonstrated minimal further improvement or even worsening of outcome scores between 3- and 12-months postoperatively (p<0.02). Both the 3-month OKS (OR=1.15, p<0.001), and knee flexion (OR=1.03, p=0.009) were significant predictors of subsequent 12-month satisfaction. CONCLUSIONS: Dissatisfaction following TKA is associated with worse outcomes as early as 3months following surgery, with minimal further improvement subsequently achieved at 12-months. Early postoperative assessment following TKA should therefore be considered, including clinical assessment, to identify those patients at risk of dissatisfaction.

Early revisions of the Femoro-Patella Vialla joint replacement.

The aim of this study was to review the early outcome of the Femoro-Patella Vialla (FPV) joint replacement. A total of 48 consecutive FPVs were implanted between December 2007 and June 2011. Case-note analysis was performed to evaluate the indications, operative histology, operative findings, post-operative complications and reasons for revision. The mean age of the patients was 63.3 years (48.2 to 81.0) and the mean follow-up was 25.0 months (6.1 to 48.9). Revision was performed in seven (14.6%) at a mean of 21.7 months, and there was one re-revision. Persistent pain was observed in three further patients who remain unrevised. The reasons for revision were pain due to progressive tibiofemoral disease in five, inflammatory arthritis in one, and patellar fracture following trauma in one. No failures were related to the implant or the technique. Trochlear dysplasia was associated with a significantly lower rate of revision (5.9% vs 35.7%, p = 0.017) and a lower incidence of revision or persistent pain (11.8% vs 42.9%, p = 0.045). Focal patellofemoral osteoarthritis secondary to trochlear dysplasia should be considered the best indication for patellofemoral replacement. Standardised radiological imaging, with MRI to exclude overt tibiofemoral disease should be part of the pre-operative assessment, especially for the non-dysplastic knee.

The effects of age on patient-reported outcome measures in total knee replacements.

We present a comparison of patient-reported outcomes (PROMs) in relation to patient age, in patients who had received a total (TKR) or unicompartmental knee replacement (UKR). The outcome was evaluated using the Oxford knee score (OKS), EuroQol (EQ-5D) and satisfaction scores. Patients aged 65 to 84 years demonstrated better pre-operative function scores than those aged < 65 years (OKS, p = 0.03; EQ-5D, p = 0.048) and those aged ≥ 85 years (OKS, p = 0.03). Post-operative scores were comparable across age groups, but a linear trend for greater post-operative improvement in OKS and EQ-5D was seen with decreasing age (p < 0.033). The overall mean satisfaction score at six months was 84.9, but those aged < 55 years exhibited a lower mean level of satisfaction (78.3) compared with all other age groups (all p < 0.031). The cumulative overall two-year revision rate was 1.3%. This study demonstrates that good early outcomes, as measured by the OKS and EQ-5D, can be anticipated following knee replacement regardless of the patient's age, although younger patients gain greater improvement. However, the lower satisfaction in those aged < 55 years is a concern, and suggests that outcome is not fully encapsulated by the OKS and EQ-5D evaluation, and raises the question whether the OKS alone is an appropriate measure of pain and function in younger, more active individuals.

Long-term trends in the Oxford knee score following total knee replacement.

The Oxford knee score (OKS) is a validated and widely accepted disease-specific patient-reported outcome measure, but there is limited evidence regarding any long-term trends in the score. We reviewed 5600 individual OKS questionnaires (1547 patients) from a prospectively-collected knee replacement database, to determine the trends in OKS over a ten-year period following total knee replacement. The mean OKS pre-operatively was 19.5 (95% confidence interval (CI) 18.8 to 20.2). The maximum post-operative OKS was observed at two years (mean score 34.4 (95% CI 33.7 to 35.2)), following which a gradual but significant decline was observed through to the ten-year assessment (mean score 30.1 (95% CI 29.1 to 31.1)) (p < 0.001). A similar trend was observed for most of the individual OKS components (p < 0.001). Kneeling ability initially improved in the first year but was then followed by rapid deterioration (p < 0.001). Pain severity exhibited the greatest improvement, although residual pain was reported in over two-thirds of patients post-operatively, and peak improvement in the night pain component did not occur until year four. Post-operative OKS was lower for women (p < 0.001), those aged < 60 years (p < 0.003) and those with a body mass index > 35 kg/m(2) (p < 0.014), although similar changes in scores were observed. This information may assist surgeons in advising patients of their expected outcomes, as well as providing a comparative benchmark for evaluating longer-term outcomes following knee replacement.

Drug bioactivation and protein adduct formation in the pathogenesis of drug-induced toxicity.

Adverse drug reactions (ADRs) remain a major complication of drug therapy and can be classified as 'on-target' or 'off-target' (idiosyncratic) reactions. On-target reactions can be predicted from the known primary or secondary pharmacology of the drug and often represent an exaggeration of the pharmacological effect of the drug. In contrast, off-target adverse reactions cannot be predicted from knowledge of the basic pharmacology of the drug. The exact mechanisms of idiosyncratic drug reactions are still unclear; however it is believed that they can be initiated by chemically reactive drug metabolites. It is well known that xenobiotics can undergo metabolic bioactivation reactions which have the potential to cause cellular stress and damage. Bioactivation of drugs is thought to have the potential of initiating covalent linkages between cellular protein and drugs which can be recognised by the adaptive immune system in the absence of detectable cellular stress. This process cannot yet be predicted in pre-clinical models or discovered in clinical trials. Because of this hazard perception, the formation of chemically reactive metabolites in early drug discovery remains a serious impediment to the development of new medicines and can lead to withdrawal of an otherwise effective therapeutic agent. The fear of such reactions occurring at the post-licensing stage - when such problems first become evident - is a major contribution to drug attrition. The first step towards such methodology has been the development of chemically reactive metabolite screens. The chemical basis of drug bioactivation can usually be rationalised and synthetic strategies put in place to prevent such bioactivation. However, there is no simple correlation between drug bioactivation in vitro and adverse drug reactions in the clinic. Such a chemical approach is clearly limited by the facts that (a) not all drugs that can undergo bioactivation by human drug-metabolising enzymes are associated with hypersensitivity in the clinic and (b) drug bioactivation may not always be a mandatory step in drug hypersensitivity. To predict such reactions in early drug development, it will require an integrated understanding of the chemical, immunological and genetic basis of adverse drug reactions in patients, which in turn will depend on the development of novel in vitro experimental systems.

Role of reactive metabolites in drug-induced hepatotoxicity.

Drugs are generally converted to biologically inactive forms and eliminated from the body, principally by hepatic metabolism. However, certain drugs undergo biotransformation to metabolites that can interfere with cellular functions through their intrinsic chemical reactivity towards glutathione, leading to thiol depletion, and functionally critical macromolecules, resulting in reversible modification, irreversible adduct formation, and irreversible loss of activity. There is now a great deal of evidence which shows that reactive metabolites are formed from drugs known to cause hepatotoxicity, such as acetaminophen, tamoxifen, isoniazid, and amodiaquine. The main theme of this article is to review the evidence for chemically reactive metabolites being initiating factors for the multiple downstream biological events culminating in toxicity. The major objectives are to understand those idiosyncratic hepatotoxicities thought to be caused by chemically reactive metabolites and to define the role of toxic metabolites.

Mechanism-based bioanalysis and biomarkers for hepatic chemical stress.

Adverse drug reactions, in particular drug-induced hepatotoxicity, represent a major challenge for clinicians and an impediment to safe drug development. Novel blood or urinary biomarkers of chemically-induced hepatic stress also hold great potential to provide information about pathways leading to cell death within tissues. The earlier pre-clinical identification of potential hepatotoxins and non-invasive diagnosis of susceptible patients, prior to overt liver disease is an important goal. Moreover, the identification, validation and qualification of biomarkers that have in vitro, in vivo and clinical transferability can assist bridging studies and accelerate the pace of drug development. Drug-induced chemical stress is a multi-factorial process, the kinetics of the interaction between the hepatotoxin and the cellular macromolecules are crucially important as different biomarkers will appear over time. The sensitivity of the bioanalytical techniques used to detect biological and chemical biomarkers underpins the usefulness of the marker in question. An integrated analysis of the biochemical, molecular and cellular events provides an understanding of biological (host) factors which ultimately determine the balance between xenobiotic detoxification, adaptation and liver injury. The aim of this review is to summarise the potential of novel mechanism-based biomarkers of hepatic stress which provide information to connect the intracellular events (drug metabolism, organelle, cell and whole organ) ultimately leading to tissue damage (apoptosis, necrosis and inflammation). These biomarkers can provide both the means to inform the pharmacologist and chemist with respect to safe drug design, and provide clinicians with valuable tools for patient monitoring.

alpha(1)-Adrenoceptor antagonists prevent paracetamol-induced hepatotoxicity in mice.

BACKGROUND AND PURPOSE: Paracetamol, a major cause of acute liver failure (ALF) represents a significant clinical problem. Adrenoceptor stimulation or antagonism can modulate chemical-induced hepatotoxicity. We investigated the role of endogenous catecholamines and alpha(1)-adrenoceptors in the development of paracetamol- induced hepatotoxicity. EXPERIMENTAL APPROACH: Paracetamol (3.5 mmol kg(-1)) was administered to male CD-1 mice, with and without alpha(1)-adrenoceptor antagonists (prazosin, doxazosin, terazosin and tamsulosin; 35.7 micromol kg(-1)). Serum transaminases and hepatic glutathione (GSH) levels were assessed as markers of hepatic damage. Paracetamol bioactivation was assessed by covalent binding, hepatic and urinary conjugate formation and uridine glucuronosyltransferase activity. Plasma catecholamines levels and hepatic congestion were also analysed. KEY RESULTS: Plasma catecholamine levels were significantly elevated 5 h post paracetamol administration. Prazosin prevented hepatotoxicity when administered 1 h before a toxic paracetamol insult and importantly, when administered up to 1 h post paracetamol injection. Prazosin had no effect on paracetamol-induced depletion of hepatic GSH, paracetamol bioactivation or paracetamol-induced transcription of defence genes. Paracetamol toxicity is associated with marked accumulation of erythrocytes within hepatic sinusoids and prazosin completely prevented this accumulation. CONCLUSION AND IMPLICATIONS: Paracetamol-induced hepatocellular damage is associated with increased circulating catecholamines. alpha(1)-Adrenoceptor antagonists conferred complete protection from paracetamol -induced hepatotoxicity. Protection was associated with absence of hepatic erythrocyte accumulation. Increased catecholamine levels may contribute to the pathophysiology of paracetamol-induced hepatotoxicity by compromising hepatic perfusion. Protection against paracetamol toxicity by alpha(1) antagonists in mice has implications for therapeutic management of patients presenting with paracetamol overdose and ALF.

Design of low-loss and highly birefringent hollow-core photonic crystal fiber.

A practical hollow-core photonic crystal fiber design suitable for attaining low-loss propagation is analyzed. The geometry involves a number of localized elliptical features positioned on the glass ring that surrounds the air core and separates the core and cladding regions. The size of each feature is tuned so that the composite core-surround geometry is antiresonant within the cladding band gap, thus minimizing the guided mode field intensity both within the fiber material and at material/air interfaces. A birefringent design, which involves a 2-fold symmetric arrangement of the features on the core-surround ring, gives rise to wavelength ranges where the effective index difference between the polarization modes is larger than 10(-4). At such high birefringence levels, one of the polarization modes retains favorable field exclusion characteristics, thus enabling low-loss propagation of this polarization channel.

Visualizing the photonic band gap in hollow core photonic crystal fibers.

The light radiated from the guided mode of a hollow core photonic crystal fiber into free space is measured as a function of angle and wavelength. This enables the direct experimental visualization of the photonic band gap and the identification of localized modes of the core region.

Time course toxicogenomic profiles in CD-1 mice after nontoxic and nonlethal hepatotoxic paracetamol administration.

Adverse drug reactions are a major clinical problem. Drug-induced hepatotoxicity constitutes a large percentage of these reactions. A thorough understanding of the genetic events, specifically, the early "decision-making" processes underlying biological changes caused by drugs and metabolites, is required. To assist in the understanding of these events, we have employed the model hepatotoxin, paracetamol (APAP), and GeneChip technology to investigate global genetic events seen after nontoxic and toxic doses in the mouse. Mice were dosed [vehicle, nontoxic APAP (1 mmol/kg), and toxic APAP (3.5 mmol/kg)], and individual hepatic RNA samples were hybridized to separate chips to determine interanimal variation. Statistical analysis detected 175 CD-1 mouse genes that were significantly regulated (P < 4.1 x 10(-6)), and nonsignificant genes were discarded. For clarity, the significantly regulated genes were then binned into categories according to their major function-antioxidant, glutathione, metabolism, transcription, immune, and apoptosis. There was no hepatic stress observed after dosing 1 mmol/kg APAP, when measured by serum alanine aminotransferase levels. Hepatic toxicity was observed at both 4 and 24 h after a 3.5 mmol/kg dose of APAP. Time course expression profiles for selected genes have been created. These results demonstrate that most active gene expression occurs around 4 h after a toxic dose of APAP. Down-regulation of these genes is observed over 24 h, coinciding with the development of overt toxicity. These data provide a deeper understanding of the in vivo time course of physiological responses of the liver to chemical stress and provide a logical step forward for the investigation of new chemical entities demonstrated positive in chemically reactive metabolite screens. The complete data set can be viewed at http://www.ebi.ac.uk/arrayexpress/. The accession number is E-MEXP-82.

Are chemically reactive metabolites responsible for adverse reactions to drugs?

Low molecular weight organic chemicals can be transformed by normal drug-metabolising systems into short-lived metabolites that are inherently reactive towards cellular macromolecules. There is direct evidence that the formation of such chemically reactive metabolites may lead to mutagenesis, carcinogenicity, apoptosis and necrosis in both cell and animal models. A number of drugs associated with non-pharmacological drug toxicities in man have been shown to undergo bioactivation either in vivo or in vitro. We have therefore examined the evidence for the role of reactive metabolites in the three most common drug-induced toxicities: hepatotoxicity, skin reactions and blood dyscrasias.

Bone gains and losses follow seasonal training and detraining in gymnasts.

The response of the human skeleton to high magnitude loading and unloading is poorly understood. Our aim was to evaluate changes in bone mineral density (BMD) in a group of intercollegiate gymnasts (n = 8, age = 18.6+/-0.8 years) over 24 months that included two 8-month competitive seasons and two 4-month offseasons. BMD of the hip, spine, and whole body was evaluated by DXA (Hologic QDR-1000/W) at baseline, 8, 12, 20, and 24 months. Results indicated significant seasonal trends in BMD of the femoral neck, trochanter, total hip, lumbar spine, and whole body. Specifically, there was a strikingly consistent pattern of bone density increases over the training seasons followed by clear declines in the offseasons. Increases at the spine were 3.5% and 3.7% followed by declines of 1.5% and 1.3% in the offseasons. Total hip BMD increased 2.3% and 1.9% during the competitive seasons followed by decreases of 1.5% and 1.2% in the offseasons. We observed a significant 24-month increase of 4.3% in spine BMD but no significant overall change at the hip. In conclusion, the human skeleton demonstrated a measurable response to high magnitude loading and unloading that was consistent across bone sites over 24 months of observation.

Reactive metabolites and their role in drug reactions.

Adverse drug reactions are a major clinical problem and often preclude drug administration. Drug hypersensitivity (or allergy) represents one of the most severe and unpredictable reactions associated with drug therapy. Our current understanding of drug hypersensitivity is based on the hapten hypothesis of immune recognition of drugs by T cells. The onset of hypersensitivity involves drug bioactivation, covalent binding, followed by uptake, antigen processing and T cell proliferation. There is convincing evidence that drugs associated with a high incidence of hypersensitivity are converted to protein reactive intermediates by the normal processes of drug metabolism and stimulate a cellular immune response in sensitive individuals. Until recently, however, there has been little evidence to relate the formation of a reactive metabolite to the initiation of a cellular immune response. The purpose of this review is to detail recent advances in our understanding of the complex mechanisms of drug hypersensitivity, and using severe skin reactions as an example, assess recent evidence that supports the hapten hypothesis of drug hypersensitivity.

Induction of metabolism-dependent and -independent neutrophil apoptosis by clozapine.

Clozapine, an atypical antipsychotic used in the treatment of refractory schizophrenia, causes neutropenia and agranulocytosis in 3 and 0.8% of patients, respectively. Clozapine undergoes bioactivation to a chemically reactive nitrenium ion, which has been shown to cause neutrophil cytotoxicity. To define further the mechanism of cell death, we have investigated the toxicity of clozapine, its stable metabolites, and its chemically reactive nitrenium ion to neutrophils and lymphocytes. Clozapine was able to induce neutrophil apoptosis at therapeutic concentrations (1-3 microM) only when it was bioactivated to the nitrenium ion. The parent drug caused apoptosis at supratherapeutic concentrations (100-300 microM) only. Neutrophil apoptosis induced by the nitrenium ion, but not by the parent drug itself, was inhibited by antioxidants and genistein and was accompanied by cell surface haptenation (assessed by flow cytometry) and glutathione depletion. Dual-color flow cytometry showed that neutrophils that were haptenated were the same cells that underwent apoptosis. No apoptosis of lymphocytes was evident with the nitrenium ion or the parent drug, despite the fact that the former caused cell surface haptenation, glutathione depletion, and loss of membrane integrity. Demethylclozapine, the major stable metabolite in vivo, showed a profile that was similar to, although less marked than that observed with clozapine. N-oxidation of clozapine or replacement of the nitrogen (at position 5) by sulfur produced compounds that were entirely nontoxic to neutrophils. In conclusion, the findings of the study expand on potential mechanisms of clozapine-induced cytotoxicity, which may be of relevance to the major forms of toxicity encountered in patients taking this drug.

Multidomain and multifunctional glycosyl hydrolases from the extreme thermophile Caldicellulosiruptor isolate Tok7B.1.

DNA sequencing techniques have revealed widespread molecular diversity of the genomic organization of apparently closely related bacteria (as judged from SSU rDNA sequence similarity). We have previously described the extreme thermophile Caldicellulosiruptor saccharolyticus, which is unusual in possessing multi-catalytic, multidomain arrangements for the majority of its glycosyl hydrolases. We report here the sequencing of three gene clusters of glycosyl hydrolases from Caldicellulosiruptor sp. strain Tok7B.1. These clusters are not closely linked, and each is different in its organization from any described for Cs. saccharolyticus. The catalytic domains of the enzymes belong to glycosyl hydrolase families 5, 9, 10, 43, 44, and 48. The cellulose binding domains (CBDs) of these enzymes from Caldicellulosiruptor sp. Tok7B.1 are types IIIb, IIIc, or VI. A number of individual catalytic and binding domains have been expressed in Escherichia coli, and biochemical data are reported on the purified enzymes for cellulose degradation encoded by engineered derivatives of celB and celE.

Purification and characterization of extracellular lipases from Ophiostoma piliferum.

Interest in lipases from microorganisms, animals, and plants has greatly increased in the past decade due to their applications in biotransformations and organic syntheses. We are reporting the purification and characterization of two lipases from the fungus, Ophiostoma piliferum, a saprophytic organism commonly found on wood. A major and a minor lipase have been co-purified by hydrophobic interaction chromatography on octyl sepharose FF, followed by ion exchange chromatography on Q sepharose FF. The lipases bound very tightly to octyl sepharose resulting in greater than 100-fold purification in this one step. The major lipase has a molecular weight of approximately 60 kDa, a pI of 3.79, and is glycosylated as determined by PAS staining. The minor lipase, which composes 10% of the total protein, has a pI of 3.6, and molecular weight of approximately 52 kDa and did not stain with the PAS reagent. Deglycosylation of the major lipase produced two proteins of lower molecular weight, a 55 kDa protein and a 52 kDa protein. The deglycosylated protein at 52 kDa co-migrates with the minor lipase on SDS-PAGE gels. N-terminal amino acid sequencing of the major and minor lipases indicated both lipases have the same N-termini and MALDI-TOF mass spectral analysis showed similar peptide patterns. Available data indicate that the lipases are derived from the same protein and appear to differ in their post-translational modification as evidenced by their pIs and molecular weight difference. The pH rate profile and thermal stability were determined for the purified O. piliferum lipase and were consistent with a mesophilic lipase. In aqueous solution, the lipases exhibited a higher rate of hydrolysis for p-nitrophenylbutyrate (C4) than for p-nitrophenylstearate (C18), which is an unexpected result.

Metabolism-dependent neutrophil cytotoxicity of amodiaquine: A comparison with pyronaridine and related antimalarial drugs.

Life-threatening agranulocytosis and hepatotoxicity during prophylactic administration of amodiaquine have led to its withdrawal. Agranulocytosis is thought to involve bioactivation to a protein-reactive quinoneimine metabolite. The toxicity of amodiaquine and the lack of cheap drugs have prompted a search for alternative antimalarial agents. The aim of this study was to determine the metabolism and neutrophil toxicity of amodiaquine, pyronaridine, and other related antimalarial agents. Horseradish peroxidase and hydrogen peroxide were used to activate drugs to their respective quinoneimine metabolites. Metabolites were trapped as stable glutathione conjugates, prior to analysis by LC/MS. Amodiaquine was metabolized to a polar metabolite (m/z 661), identified as a glutathione adduct. Tebuquine was converted to two polar metabolites. The principal metabolite (m/z 686) was derived from glutathione conjugation and side chain elimination, while the minor metabolite gave a protonated molecule (m/z 496). Only parent ions were identified when chloroquine, cycloquine, or pyronaridine was incubated with the activating system and glutathione. Calculation of the heat of formation of the drugs, however, demonstrated that amodiaquine, tebuquine, cycloquine, and pyronaridine readily undergo oxidation to their quinoneimine. None of the antimalarial compounds depleted the level of intracellular glutathione (1-300 microM) when incubated with neutrophils alone. Additionally, with the exception of tebuquine, no cytotoxicity below 100 microM was observed. In the presence of the full activating system, however, all compounds except chloroquine resulted in depletion of the level of glutathione and were cytotoxic. Pretreating the cells with glutathione and other antioxidants inhibited metabolism-dependent cytotoxicity. In summary, our data show that amodiaquine and related antimalarials containing a p-aminophenol moiety undergo bioactivation in vitro to chemically reactive and cytotoxic intermediates. In particular, pyronaridine, which is currently being investigated in humans, was metabolized to a compound which was toxic to neutrophils. Thus, the possibility that it will cause agranulocytosis in clinical practice cannot be excluded, and will require careful monitoring.

Bilateral fascia iliaca catheters for postoperative pain control after bilateral total knee arthroplasty: a case report and description of a catheter technique.

BACKGROUND AND OBJECTIVES: The pain following total knee arthroplasty can be associated with significant morbidity, especially in the elderly. Regional anesthetic techniques attenuate or eliminate postoperative pain, which may reduce this morbidity. METHODS: A 74-year-old patient with history of an epidural abscess underwent elective bilateral total knee arthroplasty for degenerative joint disease. Bilateral lumbar plexus catheters were placed via the fascia iliaca compartments. Lidocaine was infused postoperative through both catheters, and serum lidocaine levels were followed. RESULTS: The patient received significant postoperative pain relief based on physical and subjective examination. There were no complications or untoward effects related to the technique. CONCLUSION: Lumbar plexus blockade with continuous local anesthetic infusion via the fascia iliaca compartment is an effective means of providing postoperative analgesia after total knee arthroplasty when epidural analgesia is contraindicated.