Pain chronification impacts whole-brain functional connectivity in women with hip osteoarthritis during pain stimulation.

OBJECTIVE: Previous neuroimaging studies have shown that patients with chronic pain display altered functional connectivity across distributed brain areas involved in the processing of nociceptive stimuli. The aim of the present study was to investigate how pain chronification modulates whole-brain functional connectivity during evoked clinical and tonic pain. METHODS: Patients with osteoarthritis of the hip (n = 87) were classified into 3 stages of pain chronification (Grades I-III, Mainz Pain Staging System). Electroencephalograms were recorded during 3 conditions: baseline, evoked clinical hip pain, and tonic cold pain (cold pressor test). The effects of both factors (recording condition and pain chronification stage) on the phase-lag index, as a measure of neuronal connectivity, were examined for different frequency bands. RESULTS: In women, we found increasing functional connectivity in the low-frequency range (delta, 0.5-4 Hz) across pain chronification stages during evoked clinical hip pain and tonic cold pain stimulation. In men, elevated functional connectivity in the delta frequency range was observed in only the tonic cold pain condition. CONCLUSIONS: Across pain chronification stages, we found that widespread cortical networks increase their synchronization of delta oscillations in response to clinical and experimental nociceptive stimuli. In view of previous studies relating delta oscillations to salience detection and other basic motivational processes, our results hint at these mechanisms playing an important role in pain chronification, mainly in women.

Femoral nerve blockade versus local infiltration analgesia for primary knee arthroplasty. Randomised controlled trial.

INTRODUCTION: Total knee arthroplasty (TKA) is associated with severe postoperative pain and significant chronification. The lengthy debate is on-going regarding the best balance between pain management, safety, and functional rehabilitation. MATERIAL AND METHODS: Fifty adult patients scheduled for primary unilateral TKA were randomly divided into 2 groups: continuous femoral nerve blockade (FNB; n = 25) and local infiltration analgesia (LIA; n = 25). We compared FNB and LIA in terms of function (primary outcome; number of steps, recorded using a step-tracking watch), pain scores using the visual analogue scale (VAS), opioid consumption (morphine equivalents), muscle strength (Janda Score), side effects, and complications until postoperative day 5. The results are presented as (mean ± SD). RESULTS: After excluding one patient, 49 were analysed (25 FNB, 24 LIA). There were no differences between the groups in the primary outcome. The VAS score (day 0: 23 ± 17.7 vs. 32.8 ± 21.5; P = 0.101; day 1: 31.0 ± 22.3 vs. 41.7 ± 25.3; P = 0.112) and mean opioid consumption (day 0: 0.39 ± 0.17 vs. 0.50 ± 0.38; P = 0.655; day 1: 0.60 ± 0.27 vs. 0.71 ± 0.38; P = 0.406) did not differ significantly between the groups. Muscle strength was significantly lower in the FNB group on days 0 (3.05 ± 1.67 vs. 4.35 ± 0.91; P = 0.009) and 1 (2.71 ± 1.57 vs. 3.67 ± 1.18; P = 0.030). Side effects and complications had a similarly low incidence in both groups, and except for constipation (FNB < LIA) no difference was seen. CONCLUSIONS: Based on the results of this study, both FNB and LIA are associated with similar outcomes, and one cannot be recommended over the other.

The virtue of optimistic realism - expectation fulfillment predicts patient-rated global effectiveness of total hip arthroplasty.

BACKGROUND: Emerging evidence highlights the importance of preoperative expectations in predicting patient-reported outcomes of orthopedic surgeries. To date, it is still a matter of controversy whether patient satisfaction can be maximized by promoting either optimistic or realistic outcome expectations before surgery. Adjusting overly optimistic outcome expectancies in favor of a more realistic outlook on the limitations of total hip arthroplasty could reduce the risk of disappointment and lead to greater satisfaction with surgery outcomes. Our prospective cohort study was aimed at comparing the relative predictive influence of baseline expectations, expectation fulfillment and symptomatic improvement on the global effectiveness of total hip arthroplasty. METHODS: Ninety patients (49 female, 41 male; mean age: 63 ± 12.87 years) fulfilled inclusion criteria and completed a comprehensive preoperative assessment comprising sociodemographic, clinical, functional and psychological phenotypes. Moreover, the strengths of preoperative expectations for improvements in eight pain-related and functional domains were recorded on a 5-point Likert-scale. At 12 months after surgery, patients were asked to rate perceived improvements in each of these domains as well as the global effectiveness of the total hip replacement on a 5-point Likert-scale. To evaluate the relative impact of preoperative expectations, symptom improvement and the fulfillment of expectations on the global effectiveness of surgery, a sequential multiple regression analysis was performed. RESULTS: Compared with the actual improvement at 12-months follow-up, prior expectations had been overly optimistic in about 28% of patients for hip pain, in about 45% for walking ability and around 60% for back pain, independence in everyday life, physical exercise, general function social interactions and mental well-being. An optimistic hip pain expectation, walking ability at baseline and the fulfillment of expectations for walking ability, general function and independence in everyday life were found to independently predict global effectiveness ratings. CONCLUSIONS: Positive expectation about pain and the fulfillment of expectations concerning functional domains predicted higher global effectiveness ratings. In line with many authors investigating the relationship between the fulfillment of expectations and satisfaction with medical interventions, we suggest that professionals should explicitly address their patients' expectations during the preoperative education and consultation.

The influence of pain expectation on pain experience after orthopedic surgery: an observational cohort study.

BACKGROUND: Current literature about the effects of patients' expectations on relevant outcome measures is still conflicting and incomplete. The aim of this prospective observational study was to assess the influence of expectations and the fulfillment of expectations on postoperative pain intensity and pain relief. Furthermore, clinical characteristics influencing expectations and the fulfillment of expectations were explored. METHODS: Patients undergoing elective orthopedic surgery were assessed using two standardized self-report questionnaires on the day before surgery and the third postoperative day. One hundred and seventy patients from 21 to 93 years (average age 64.6, SD 14.0 years; 55% female) were consecutively included. RESULTS: While expectations of pain intensity did not correlate with pain experience after surgery, the fulfillment of expectations was associated with postoperative pain experience. Patients whose expectations were fulfilled were found to be more satisfied with the overall treatment as compared to those whose expectations were not fulfilled. Higher levels of expected pain were associated with higher fear of surgery and fear of postoperative pain. Preoperative pain intensity, length of treatment before the surgery, fear of surgery, helplessness and fear of postoperative pain were associated with higher postoperative pain intensity. Lower levels of preoperative fear of surgery and fear of postoperative pain were found to correlate with the fulfillment of pain relief. CONCLUSIONS: Our study indicates that postoperative pain and satisfaction with the treatment are associated with the degree of fulfillment of expectations rather than the expected pain itself.

Coagulation monitoring and transfusion in major non-emergency orthopaedic surgery - An observational study.

OBJECTIVE: Perioperative coagulation monitoring and transfusions were evaluated. METHODS: 70 cases were included. Time points: before (PRE), after surgery (POST), day 1, day 3, day 7. Standard and patient near tests were assessed. Groups were: Transfused (TG); Control (CG). RESULTS: 23 patients were transfused (TG), 47 were not (CG). PRE haemoglobin was reduced, coagulation time (CT) was prolonged in TG. FIBTEM decrease was higher in TG. Leukocytes were elevated in TG. ASPI decreased, TRAP and ADP aggregability increased in both groups. CONCLUSION: CT, haemoglobin and fibrinogen were associated with transfusion. TRAP and ADP aggregability increased and could account for thromboembolism.

Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis.

BACKGROUND: Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. METHODS: The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg. RESULTS: Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05). CONCLUSION: Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype.

The cortical responses to evoked clinical pain in patients with hip osteoarthritis.

BACKGROUND: Experimental models have been used extensively to evaluate pain using e.g., visual analogue scales or electroencephalography (EEG). Stimulation using tonic pain has been shown to better mimic the unpleasantness of chronic pain, but has mainly been evoked by non-clinical stimuli. This study aims to, evaluate the EEG during clinical pain in patients scheduled for total hip replacement with control and resting conditions. METHODS: The hip scheduled for replacement was moved by the examiner to evoke pain for 30 seconds while recording EEG. The control condition entailed movement of the opposite hip in a similar fashion and holding it for 30 seconds. In addition, EEG was recorded during the resting condition with open eyes. The relative spectral content was calculated from the EEG as well as functional connectivity using phase-lag index for frequency bands delta (1-4Hz), theta (4-8Hz), alpha (8-12Hz) and beta (12-32Hz). A mixed model was used for statistical comparison between the three recording conditions. RESULTS: Spectral content differed between conditions in all bands. Functional connectivity differed in delta and theta frequency bands. Post-hoc analysis revealed differences between the painful and control condition in delta, theta and beta for spectral content. Pain during the hip rotation was correlated to the theta (r = -0.24 P = 0.03) and beta (r = 0.25 P = 0.02) content in the EEG. CONCLUSION: EEG differences during hip movements in the affected and unaffected hip appeared in the spectral beta and theta content. This was correlated to the reported pain perceived, pointing towards pain specific brain activity related to clinical pain.

Clinical relevance of persistent postoperative pain after total hip replacement - a prospective observational cohort study.

PURPOSE: The development of persistent postoperative pain may occur following surgery, including total hip replacement. Yet, the prevalence may depend on the definition of persistent pain. This observational cohort study explored whether the prevalence of persistent pain after total hip replacement differs depending on the definition of persistent pain and evaluated the impact of ongoing pain on the patient's quality of life 6 months after surgery. PATIENTS AND METHODS: Pre- and postoperative characteristics of 125 patients undergoing elective total hip replacement were assessed and 104 patients were available for the follow-up interview, 6 months after surgery. RESULTS: Six months after surgery, between 26% and 58% of patients still reported hip pain - depending on the definition of persistent pain. Patients with moderate-to-severe persistent pain intensity (>3 on a numerical rating scale) were more restricted in their daily life activities (Chronic Pain Grade - disability score) but did not differ in reported quality of life (Short-Form 12) from those with no pain or milder pain intensity. Maximal preoperative pain intensity and body mass index were the only independent factors influencing daily function 6 months after total hip replacement. CONCLUSION: These findings support a high prevalence of persistent postoperative pain after total hip replacement and a large variability depending on the definition used. There was a close relation between physical functioning and pain as well as relevance of the patient's psychological state at the time of the operation.

The Influence of Chronic Pain on Postoperative Pain and Function After Hip Surgery: A Prospective Observational Cohort Study.

UNLABELLED: Pre-existing or chronic pain is an established risk factor for severe postoperative pain. In this prospective observational cohort study, we investigated whether a history of chronic pain, beyond the presence of hip-related pain, affected other postoperative factors including early mobilization, function, and psychological distress after hip surgery. Patients who underwent total hip replacement surgery were observed from the preoperative day until the seventh postoperative day. Before surgery, they were characterized by their pain history, pain intensity, function, and psychological characteristics. Postoperatively, pain intensity was evaluated on day 1, 3, 5, and 7 and the analgesic consumption was recorded for each of these days. Measures of function (functional questionnaire, ability to mobilize and to climb stairs, and range of hip motion) and psychological distress were re-evaluated on day 7. A history of chronic pain was associated with slower postoperative mobilization, poorer physical function, and greater psychological distress in addition to increased postoperative pain intensity. The comorbidity of a chronic pain disorder resulted in greater pain intensity after surgery, and also impeded postoperative rehabilitation. Identification of patients with a chronic pain disorder is necessary preoperatively so that appropriate pain management and rehabilitation can be planned to facilitate recovery. PERSPECTIVE: Chronic pain, beyond the presence of hip-related pain, is associated with slower postoperative mobilization, poorer physical function, and greater psychological distress after total hip replacement surgery. Identification of patients with chronic pain and establishment of multiprofessional perioperative management might improve postoperative rehabilitation of patients with chronic pain.

Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients.

BACKGROUND: Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables. METHODS: This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran-Mantel-Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting. RESULTS: Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding events within 24 h (classified by an independent, blinded Adjudication Committee) were reported in 17 (2.9%) sugammadex and 24 (4.1%) usual care patients (relative risk [95% CI], 0.70 [0.38 to 1.29]). Compared with usual care, increases of 5.5% in activated partial thromboplastin time (P < 0.001) and 3.0% in prothrombin time (P < 0.001) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min. There were no significant differences between sugammadex and usual care for other blood loss measures (transfusion, 24-h drain volume, drop in hemoglobin, and anemia), or risk of venous thromboembolism, and no cases of anaphylaxis. CONCLUSION: Sugammadex produced limited, transient (<1 h) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care.

Thyroid gland rupture: a rare case of respiratory distress.

BACKGROUND: Rupture of a normal thyroid gland after blunt cervical trauma is a rare case of airway compression. This case report describes the case of a 79-year-old woman who developed severe respiratory distress after a bicycle crash. CASE REPORT: Presenting about 2 h after the crash, the patient noted cervical swelling and increasing dyspnea. The diagnosis of thyroid gland rupture was made with a combination of computed tomography scan, cervical radiography, and bronchoscopy. Invasive airway management was required in the first few hours after the crash. The patient underwent a left hemithyroidectomy, and recovered without complications. CONCLUSION: This case report highlights the fact that thyroid gland rupture can be a threatening complication of blunt cervical trauma.

Adrenoceptor stimulation does not affect ICAM-1 and VCAM-1 expression in vitro.

BACKGROUND: Endothelial adhesion molecules ICAM-1 (CD54) and VCAM-1 (CD106) mediate cellular adhesion and transcellular migration. Cell adhesion and diapedesis have a key role in the course of shock and sepsis. During severe sepsis, adrenoceptor agonist levels may be increased due to endogenous production or due to intensive care treatment. As yet, the influence of ß1 or ß2 agonists on adhesion molecule formation on endothelial cells has remained unclear. METHODS: Cultured human umbilical vein endothelial cells were stimulated with E. coli. Following bacterial stimulation the cells were incubated with either ß2 receptor agonist terbutaline or ß1 agonist norepinephrine. ICAM-1 and VCAM-1 expression were examined using flow cytometry. RESULTS: Administration of norepinephrine did not cause increases of both CD54 and CD106 in stimulated HUVEC. Compared to negative controls the bacterial stimulation itself led to an increase of adhesion molecules. Following administration of terbutaline no significant increase in CD54 expression was found. CONCLUSIONS: Bacterial stimulation led to an increase of adhesion molecule expression. Adrenoceptor stimulation of activated endothelial cells did not cause significant increases of cellular adhesion molecules.

Neurogenic pulmonary edema in a fatal case of subarachnoid hemorrhage.

Neurogenic pulmonary edema (NPE) is caused by a variety of central nervous system lesions and may appear as a subclinical complication. The fulminant form of NPE is always life-threatening. Many pathophysiologic mechanisms have been implicated in the development of NPE, but the exact interaction remains unknown. We report a case of a fulminant NPE with fatal consequences associated with a subarachnoid hemorrhage. Treatment focuses on ventilatory support and measures to reduce intracranial pressure.

Rhesus immune globulin fails to prevent immunization after rhesus incompatible blood transfusion.

The transfusion of rhesus positive (D+) red blood cells to a rhesus negative (D-) person usually induces the development of an irregular anti-D antibody in the recipient. This can lead to a hemolytic reaction in subsequent transfusions, and, in women of childbearing age, can lead to fetal erythroblastosis in any future pregnancy. The recommended interventions to avoid the immunization of the recipient include the administration of intravenous rhesus immune globulin within 72 h after the transfusion. We report the case of a D- woman who received one unit of D+ red blood cells and a total of 40 units of D- red blood cells after severe trauma. In spite of treatment with rhesus immune globulin, the patient developed anti-D antibodies.

Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple-species kidney xenotransplantation model.

Clinical pig-to-human xenotransplantation might be associated with the risk of transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs). We have established a pig-to-humanised-cynomolgus monkey xenotransplantation model allowing the analysis of potential PERV-transmission from normal or transgenic porcine organs to human vascular tissue. Pig-to-human kidney xenotransplantation was performed in cynomolgus monkeys. An interposition graft constructed from a human saphena vein replaced the porcine kidney vein. After graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19 days), the human interposition grafts were removed. Human endothelial cells (huECs) were isolated from the interposition grafts and cultivated in vitro. Explanted human vascular tissue, isolated huECs, plasma and serum samples of the graft recipients were characterised by flow cytometry and immunohistochemistry and screened for indications of PERV transmission by quantitative polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and RT assay. PERV-specific immune response of recipients was analysed by Western blot. No evidence of PERV infection or PERV-specific immune response was detected.