Assessment of CT perfusion indices of the clinicoradiological response to anti-tubercular therapy in patients with intestinal tuberculosis.

AIM: To explore the possibility of using a novel technique, CT perfusion imaging, to monitor the response to anti-tubercular therapy (ATT) in patients with intestinal tuberculosis. MATERIALS AND METHODS: A prospective observational study was performed in adults with treatment naive-intestinal tuberculosis. Clinical, endoscopic, and conventional radiological findings of patients were compared at baseline and post-ATT. CT perfusion imaging was performed with recording of six perfusion parameters (blood flow, blood volume, mean transit time, time to peak, maximum peak intensity, and permeability/blood flow extraction). RESULTS: Twenty-two patients (13 women, 59%) with a median age of 25 years were recruited. The terminal ileum and ileocaecal junction were the most frequent sites of involvement (59%), with multiple segments of the intestine being involved in 16 patients (73%). Median duration of ATT was 6 months (range 6-10 months). Complete clinical response was observed in 22/22 (100%) patients, endoscopic response in 12/12 (100%) patients, and radiological response in 10/13 (76%) patients. There was a significant decrease in mean blood flow, blood volume, maximum peak intensity, and an increase in mean transit time and time to peak on follow-up CT perfusion imaging performed after 6 months of ATT. CONCLUSION: Significant alterations in CT perfusion parameters were demonstrated following treatment, consistent with a decline in inflammation and vascularity. CT perfusion imaging of the bowel is a novel means to assess the radiological response to ATT in intestinal tuberculosis, although at the cost of a higher dose of radiation exposure.

Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development.

Novel genetically modified biological control products (referred to as "GM biocontrol products") are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.

Evaluation of delay in time to adjuvant chemotherapy after HIPEC and its impact on oncological outcome in advanced epithelial ovarian cancer.

OBEJECTIVES: Optimal cytoreductive surgery (CRS), followed by adjuvant chemotherapy, is a major predictor of oncological outcome in patients with advanced epithelial ovarian carcinoma (EOC). It is not clear if a delayed start of adjuvant chemotherapy negatively impacts on the oncological outcome. METHODS: Prospective registry study on 75 patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Adjuvant chemotherapy was started within 42 days in 41 patients (55%), later on in 34 patients (45%). Multivariate analyses of preoperative factors were done on survival outcome. Outcomes were recurrence-free survival (RFS) and overall survival (OS). RESULTS: There was no difference in RFS after early introduction (median 35 months) vs. late introduction of chemotherapy (median 32 months), p = 0.17. Median OS in patients with late introduction of chemotherapy was 46 months and was not yet reached in early introduction group. CONCLUSIONS: In this exploratory study in a small group of women with advanced EOC, starting adjuvant chemotherapy more than 6 weeks after CRS and HIPEC did not deteriorate significantly RFS or OS. Well-designed clinical studies are still needed to evaluate the interplay of HIPEC and the point of time of postoperative adjuvant chemotherapy in this indication.

Awake tracheostomy in a child with respiratory distress due to retropharyngeal abscess.

Awake tracheostomy in a child with respiratory distress is an emergency life-saving procedure when risk of airway loss after induction of general anaesthesia is greater due to difficult anatomy. A 10-year-old boy presented three days after removal of a foreign body in the throat under general anaesthesia. Over the subsequent days, the patient had a progressively increasing visible swelling in the neck, stridor and respiratory distress. An urgent X-ray and computed tomography scan of the neck revealed a retropharyngeal abscess compressing the trachea. Due to anticipated difficulty in airway management under general anaesthesia, we decided to perform an awake tracheostomy. The child and the parents were counselled regarding steps of awake tracheostomy, as well as the benefits and possible risks associated with it. Topicalisation was achieved by administering glycopyrrolate, nebulisation with lidocaine 4%, and the skin was prepared with lidocaine 2% with 1:200,000 adrenaline. After the awake tracheostomy was successfully performed, general anaesthesia was induced and the retropharyngeal abscess was drained. Effective communication and building rapport is essential for safe awake tracheostomy in a child with respiratory distress when impending airway loss may occur at any moment.

Frailty is a better predictor than age for outcomes in geriatric patients with rectal cancer undergoing proctectomy.

BACKGROUND: Both frailty and older age are risk factors for adverse surgical outcomes. We hypothesized that frailty, regardless of patient age, is a predictor of poor postoperative outcome among patients with rectal cancer undergoing proctectomy. METHODS: Patients with primary rectal cancer undergoing proctectomy between 2012 to 2015 were identified in the database of the National Quality Improvement Program. The simplified, 5-item frailty index was grouped into 0, 1, 2, and ≥3. Outcomes were morbidity and 30-day mortality. RESULTS: This study involved 9,252 patients from the National Quality Improvement Program database. Increasingly frail patients had greater morbidity and mortality (P < .001). Logistic regression revealed that frailty was a predictor of morbidity (odds ratio = 6.7, P < .0001); in contrast, older age was not associated with morbidity when adjusting for frailty (odds ratio = 1.2, P = .14). Both older age and frailty were associated with greater mortality, with frailty (odds ratio = 20.8, P < .0001) more so than older age (odds ratio = 10.3, P < .0001). CONCLUSION: Frailty was more strongly associated with morbidity and mortality than older age in patients undergoing proctectomy. Surgical options can be expanded to older patients with the use of simplified, 5-item frailty index as a decision-making tool.

Cross cultural comparison of constipation profiles at tertiary care centers between India and USA.

BACKGROUND: Despite potential differences in patient perception of chronic constipation (CC) in geographically and culturally distinct regions, head-to-head studies comparing the clinical profile, constipation severity, impact on quality of life (QOL) and economic impact are lacking. METHODS: We conducted a cross-sectional cohort study of patients presenting with CC to tertiary care centers in the USA and India. Standardized instruments were used to assess constipation subtype, disease severity, disease-specific QOL, somatization, and psychiatric comorbidities. We used multivariable linear regression to determine the predictors of QOL and number of healthcare visits. KEY RESULTS: Sixty-six and 98 patients with CC were enrolled in the USA and India, respectively. Indian patients with CC had significantly more frequent bowel movements/week compared to their USA counterparts (Median 5 vs 3, P < .0001). The proportion of patients with Bristol stool form scale type 1 and 2 was significantly higher in the USA compared to India (65.5% vs 48%, P = .04). Higher depression score (P = .001), more severe constipation symptoms (P = .001) and site of the study being USA (P = .008) independently predicted worse QOL. Indian patients (P < .001) and worse QOL (P = .02) were independent predictors of number of healthcare visits in the last 12 months. CONCLUSIONS AND INFERENCES: Indian patients with CC have more frequent and softer bowel movements compared to those in the USA suggesting significant differences in perception of CC in different geographic and cultural settings. QOL and economic impact related to constipation varies with geographic/cultural setting irrespective of other clinical and psychosomatic features.

Hydrodynamically Coupled Brownian Dynamics: A coarse-grain particle-based Brownian dynamics technique with hydrodynamic interactions for modeling self-developing flow of polymer solutions.

We present a novel coarse-grain particle-based simulation technique for modeling self-developing flow of dilute and semi-dilute polymer solutions. The central idea in this paper is the two-way coupling between a mesoscopic polymer model and a phenomenological fluid model. As our polymer model, we choose Responsive Particle Dynamics (RaPiD), a Brownian dynamics method, which formulates the so-called "conservative" and "transient" pair-potentials through which the polymers interact besides experiencing random forces in accordance with the fluctuation dissipation theorem. In addition to these interactions, our polymer blobs are also influenced by the background solvent velocity field, which we calculate by solving the Navier-Stokes equation discretized on a moving grid of fluid blobs using the Smoothed Particle Hydrodynamics (SPH) technique. While the polymers experience this frictional force opposing their motion relative to the background flow field, our fluid blobs also in turn are influenced by the motion of the polymers through an interaction term. This makes our technique a two-way coupling algorithm. We have constructed this interaction term in such a way that momentum is conserved locally, thereby preserving long range hydrodynamics. Furthermore, we have derived pairwise fluctuation terms for the velocities of the fluid blobs using the Fokker-Planck equation, which have been alternatively derived using the General Equation for the Non-Equilibrium Reversible-Irreversible Coupling (GENERIC) approach in Smoothed Dissipative Particle Dynamics (SDPD) literature. These velocity fluctuations for the fluid may be incorporated into the velocity updates for our fluid blobs to obtain a thermodynamically consistent distribution of velocities. In cases where these fluctuations are insignificant, however, these additional terms may well be dropped out as they are in a standard SPH simulation. We have applied our technique to study the rheology of two different concentrations of our model linear polymer solutions. The results show that the polymers and the fluid are coupled very well with each other, showing no lag between their velocities. Furthermore, our results show non-Newtonian shear thinning and the characteristic flattening of the Poiseuille flow profile typically observed for polymer solutions.

Effect of maternal oxygen inhalation on foetal free radical activity: a prospective, randomized trial.

BACKGROUND: Maternal inhalation of 35-40% oxygen concentration has no significant effect on foetal partial pressure of oxygen, and 60-100% produced maternal and foetal hyperoxia with increased free radical activity. The benefit of 50% maternal oxygen inhalation on foetal oxygenation, oxidant stress and total antioxidant status (TAS) during Caesarean section (CS) has not been simultaneously evaluated. METHODS: In this prospective, randomized, controlled trial 120 ASA physical status I-II, term pregnant women were recruited to elective CS (n = 60) and emergency CS (n = 60) and received either 50% oxygen or air inhalation following subarachnoid block (SAB). Patients and investigators were blinded to the inhaled oxygen concentration. The primary outcome of the study was foetal umbilical artery (UA) malondialdehyde (MDA) at birth. RESULTS: In both elective and emergency CS, there was no difference in foetal oxidative stress and TAS in spite of increase in maternal PaO2. In elective CS, maternal MDA was higher at delivery in mothers breathing 50% oxygen as compared to their own baseline values (P = 0.04). In emergency CS, maternal TAS at 10 min was lower in mothers inhaling 50% oxygen as compared to air (P = 0.01). The average duration of maternal oxygen supplementation was ~10.3 min in elective and ~7.4 min in emergency CS. Neonatal outcome, episodes of maternal hypotension and oxygen desaturation were similar in both the groups. CONCLUSION: Brief duration of 50% oxygen maternal inhalation during elective or emergency CS did not significantly affect foetal MDA and TAS under SAB.

Clinical management of Brucella suis infection in dogs and implications for public health.

BACKGROUND: Brucellosis caused by Brucella suis is a notifiable disease that has recently emerged in dogs in New South Wales (NSW). Given the potential for zoonotic transmission, euthanasia of affected dogs is recommended, but this action is not mandatory. We report the clinical management of three dogs that underwent treatment at their owners' request. CASE REPORTS: A 14-month-old spayed female crossbreed originally obtained from an urban animal shelter underwent extensive investigations in 2011-12 for lameness and back pain, culminating in decompressive laminectomy. Diagnosis of multifocal discospondylitis and spinal empyema was made, with B. suis cultured from surgical biopsy specimens. The dog responded to long-term treatment using rifampicin and doxycycline. A second case of B. suis infection was diagnosed in January 2016 in a 3-year-old crossbreed pig-hunting dog with unilateral testicular enlargement. Following serological diagnosis the dog was given preliminary therapy using rifampicin and doxycycline, the affected testis was resected and the patient given a further month of combination therapy. In March 2016 a 7-year-old crossbreed pig-hunting dog with brucellosis was handled similarly, although both testes were removed. CONCLUSION: Brucellosis should be considered in the differential diagnosis of back pain, discospondylitis, lameness, abortion, prostatic abscessation and testicular/epididymal enlargement in dogs, especially if there is exposure to feral pigs or consumption of uncooked feral pig meat. Euthanasia is the only guarantee of reducing the public health risk to zero. However, where treatment is desired by the owner, combination therapy using rifampicin and doxycycline appears to be effective, when combined with surgical resection of infected tissues. Further monitoring of dogs during and after treatment is required to document cure.

Endoscopic and clinical responses to anti-tubercular therapy can differentiate intestinal tuberculosis from Crohn's disease.

BACKGROUND: Differentiation between intestinal tuberculosis and Crohn's disease is difficult and may require therapeutic trial with anti-tubercular therapy in tuberculosis-endemic regions. AIM: To evaluate the role of therapeutic trial with anti-tubercular therapy in patients with diagnostic confusion between intestinal tuberculosis and Crohn's disease. METHODS: We performed retrospective-comparative (n = 288: 131 patients who received anti-tubercular therapy before being diagnosed as Crohn's disease and 157 intestinal tuberculosis patients) and prospective-validation study (n = 55 patients with diagnostic confusion of intestinal tuberculosis/Crohn's disease). Outcomes assessed were global symptomatic response and endoscopic mucosal healing. RESULTS: In the derivation cohort, among those eventually diagnosed as Crohn's disease, global symptomatic response with anti-tubercular therapy was seen in 38% at 3 months and in 37% who completed 6 months of anti-tubercular therapy. Ninety-four per cent of intestinal tuberculosis patients showed global symptomatic response by 3 months. Endoscopic mucosal healing was seen in only 5% of patients with Crohn's disease compared with 100% of intestinal tuberculosis patients. In the validation cohort, all the patients with intestinal tuberculosis had symptomatic response and endoscopic mucosal healing after 6 months of anti-tubercular therapy. Among the patients with an eventual diagnosis of Crohn's disease, symptomatic response was seen in 64% at 2 months and in 31% who completed 6 months of anti-tubercular therapy, none had mucosal healing. CONCLUSIONS: Disproportionately lower mucosal healing rate despite an overall symptom response with 6 months of anti-tubercular therapy in patients with Crohn's disease suggests a need for repeat colonoscopy for diagnosing Crohn's disease. Patients with intestinal tuberculosis showing significant symptomatic response after 2-3 months of anti-tubercular therapy, suggest that symptom persistence after a therapeutic trial of 3 months of anti-tubercular therapy may indicate the diagnosis of Crohn's disease.

Coarse-grained simulations for flow of complex soft matter fluids in the bulk and in the presence of solid interfaces.

We present a coarse-grained particle-based simulation technique for modeling flow of complex soft matter fluids such as polymer solutions in the presence of solid interfaces. In our coarse-grained description of the system, we track the motion of polymer molecules using their centers-of-mass as our coarse-grain co-ordinates and also keep track of another set of variables that describe the background flow field. The coarse-grain motion is thus influenced not only by the interactions based on appropriate potentials used to model the particular polymer system of interest and the random kicks associated with thermal fluctuations, but also by the motion of the background fluid. In order to couple the motion of the coarse-grain co-ordinates with the background fluid motion, we use a Galilean invariant, first order Brownian dynamics algorithm developed by Padding and Briels [J. Chem. Phys. 141, 244108 (2014)], which on the one hand draws inspiration from smoothed particle hydrodynamics in a way that the motion of the background fluid is efficiently calculated based on a discretization of the Navier-Stokes equation at the positions of the coarse-grain coordinates where it is actually needed, but also differs from it because of the inclusion of thermal fluctuations by having momentum-conserving pairwise stochastic updates. In this paper, we make a few modifications to this algorithm and introduce a new parameter, viz., a friction coefficient associated with the background fluid, and analyze the relationship of the model parameters with the dynamic properties of the system. We also test this algorithm for flow in the presence of solid interfaces to show that appropriate boundary conditions can be imposed at solid-fluid interfaces by using artificial particles embedded in the solid walls which offer friction to the real fluid particles in the vicinity of the wall. We have tested our method using a model system of a star polymer solution at the overlap concentration.

I.V. paracetamol as an adjunct to patient-controlled epidural analgesia with levobupivacaine and fentanyl in labour: a randomized controlled study.

BACKGROUND: Use of i.v. paracetamol for postoperative pain is well documented, but it is unclear if it can reduce the consumption of opioids during patient-controlled epidural analgesia (PCEA) in labouring parturients. METHODS: In this randomized, double-blind, placebo-controlled clinical trial conducted in a tertiary care hospital, 80parturients were randomly assigned to two groups of 40 each, to receive either 1000 mg (100 ml) i.v. paracetamol or 100 ml normal saline as placebo, 30 min before the procedure. After insertion of the epidural catheter, all patients received 10 ml of levobupivacaine 0.1% with 2 µg ml-1 fentanyl, followed by continuous background epidural infusion of 6 ml h-1 with a provision of patient-controlled bolus 5 ml of same drug with a lock-out interval of 12 min.The primary outcome was hourly mean consumption of levobupivacaine and fentanyl mixture (ml.h-1). Secondary outcomes included pain score ,: sensory and motor block, haemodynamic parameters of mother, duration of second stage of labour, mode of delivery, Apgar scores, foetal heart rate and adverse effects. RESULTS: The hourly mean drug consumption in the Paracetamol group was significantly lower as compared with the Placebo group (7.03 ml.h-1, SD 0.83 vs. 8.12 ml.h-1, SD 1.34; p < 0.001). The mean number of boluses taken were also significantly less in the paracetamol group (1.00, SD 0.93 vs. 1.43, SD 0.90; p = 0.036). Pain scores decreased in both the groups without significant inter-group differences. CONCLUSIONS: Use of 1000 mg i.v. paracetamol decreases the mean hourly drug consumption through epidural route. Thus i.v. paracetamol is a safe and effective adjunct to PCEA in labour analgesia. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India (http://ctri.nic.in/Clinicaltrials/login.php), trial registration number 2013/09/003968.

Post-operative analgesia using intermittent vs. continuous adductor canal block technique: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Intermittent boluses for neural blockade provide better post-operative analgesia when compared to continuous infusion. However, these techniques of administration have not yet been compared while performing adductor canal block (ACB). We compared intermittent vs. continuous ACB for managing post-operative pain following anterior cruciate ligament (ACL) reconstruction. The primary endpoint was total morphine consumption for 24 h post-operatively in both the groups. Secondary outcomes included evaluation of pain scores and opioid-related side effects. METHODS: After ethics board approval, subjects presenting for ACL reconstruction were randomized to receive either continuous ACB (n = 25) with 0.5% ropivacaine infusing at 2.5 ml/h or intermittent boluses (n = 25) of 15 ml of 0.5% ropivacaine every 6 h. Total morphine consumption 24 h following surgery was recorded in each group. RESULTS: Fifty subjects completed this study. The mean 24-h total morphine consumption in the intermittent group, [11.36 (6.82) mg], was significantly reduced compared with the continuous group, [23.40 (10.45) mg] (P < 0.001). The mean visual analogue scale (VAS) pain score at rest and on knee flexion was significantly reduced in the intermittent group at 4, 6, 8, and 12 h compared with the continuous group. CONCLUSION: Intermittent ACB allowed significantly reduced consumption of morphine for 24 h in the post-operative period compared with continuous ACB when identical doses of ropivacaine were used in each group.

Sclerosing mesenteric panniculitis in a young patient : common cause of diagnostic dilemma and treatment refractoriness.

BACKGROUND: Sclerosing mesenteric panniculitis (SMP) is an idiopathic chronic fibroinflammatory disorder of the intra-abdominal fat. CASE PRESENTATION: Herin, we report a case of SMP, involving the omentum, mesentery and peri-colic fat in a 18 year old male, who presented with significant and recurrent abdominal distension for 4.5 years. Computed tomogram revealed ascites, with nodular and irregular omental thickening and foci of calcification. Non-specific radiological and histological features made an accurate diagnosis extremely difficult. After a thorough work up and exclusion of other differentials, diagnosis of a nodular SMP (Weber Christian disease) was given. After showing resistance to chemotherapeutic agents, slow response was noted with cyclophosphamide, followed by rapid symptomatic improvement with mesenterectomy. CONCLUSION: SMP is an uncommon benign mesenteric/ omental inflammation, and is a diagnosis of exclusion. As treatment refractoriness is common, management should be individualized and continued for along period. Surgical omentectomy may be helpful.

To determine block establishment time of supraclavicular brachial plexus block using blunt versus short bevel needle: A prospective randomized trial.

BACKGROUND: Unintentional intraneural injection under ultrasound guidance (USG) with fine caliber needles and lower success rate with large caliber Tuohy needles in supraclavicular brachial plexus block (SCB) have been reported. MATERIALS AND METHODS: We undertook study to standardize the use of 20-gauge short versus blunt bevel needle for SCB. After approval of Institutional Ethics Committee and written informed consent, patients were randomized using computer-generated random number table to either of the two groups; blunt bevel needle group (n = 30): SCB under USG using 20-gauge Tuohy needle or short bevel needle group (n = 30): SCB under USG using 20-gauge short bevel needle. The primary outcome of the study was time to establishment of sensory and motor block of individual nerves, and secondary outcome was tolerability and any adverse effects. RESULTS: The time to establishment of sensory and motor block in individual nerve territory was similar in both the groups. The complete sensory and motor anesthesia was achieved in 78.3% patients and complete sensory and motor anesthesia after supplementary block was achieved in 86.6% patients. Paresthesias during SCB were recorded in 15 patients. Out of these eight patients were of blunt bevel group and seven patients were of short bevel group. None of the patients experienced any neurological adverse effects. CONCLUSION: The establishment of sensory and motor blockade of individual nerves was similar to 20-gauge short and blunt bevel needle under ultrasound guide with no neurological adverse events.

Correlation of Serum Vitamin A Levels with Disease Activity Indices and Colonic IL-23R and FOXP3 mRNA Expression in Ulcerative Colitis Patients.

Genome-wide association studies have identified IL-23 receptor (IL-23R) as a susceptibility locus for the pathogenesis of ulcerative colitis (UC), which is characterized by exaggerated Th2/Th17 response. Studies have shown that vitamin A (VA) reduces disease progression by promoting FOXP3⁺ T cells and curbing Th17 cells. In this study, we explored the association of colonic IL-23R and FOXP3 expression in fifty-one UC patients (23 in remission and 28 with active disease) with serum VA levels and disease activity. We observed that decreased serum VA levels were associated with increased disease activity. However, there was no significant difference in mucosal IL-23R and FOXP3 expression in UC patients with moderate-to-severe disease activity compared to those in remission. Also, no significant correlation was drawn between serum VA levels and mucosal IL-23R and FOXP3 expression. Our study suggests that even after an established role of VA in inhibiting Th17 responses in mice models and humans, serum VA levels and disease activity do not correlate with FOXP3 and IL-23R expression in colonic mucosa of UC patients.

Effect of preoperative flupirtine on postoperative morphine sparing in patients undergoing total abdominal hysterectomy.

BACKGROUND: Flupirtine is a unique non-opioid, centrally acting analgesic with muscle relaxant properties. So far no study has evaluated, use of preoperative flupirtine on postoperative morphine sparing effect in patients undergoing total abdominal hysterectomy (TAH). MATERIALS AND METHODS: We performed a prospective, controlled, and randomized study in 50 female patients of American Society of Anesthesiologists physical status I-II, aged between 30 and 60 years scheduled for TAH under general anesthesia (GA). Patients were randomized to receive either single dose flupirtine 100 mg or placebo 1 h prior to surgery. A standard anesthetic and analgesic protocol was followed in both the groups. Postoperatively, a titrated loading dose of intravenous morphine 0.1 mg/kg was followed with patient-controlled analgesia with morphine (bolus of 0.01 mg/kg with a lockout time of 7 min). The primary outcome was cumulative morphine consumption at 48 h postoperatively. Secondary outcomes included hemodynamics, visual analog scale (VAS) at rest, VAS on cough, and any adverse effects. RESULTS: All enrolled 50 patients completed the follow-up. The cumulative mean morphine consumption (standard deviation [SD]) at 48 h (40.4 [6.0] vs. 47 [6.6] mg, P = 0.001) was reduced in-group flupirtine as compared with placebo. The cumulative mean VAS at rest (SD) (3 [0.7] vs. 3.7 [0.7], P = 0.001) and on cough (3 [0.9] vs. 3.8 [0.5], P = 0.002) were reduced in-group flupirtine as compared with placebo at 48 h postoperatively. CONCLUSION: Preoperative use of flupirtine exhibited morphine sparing effect in patients following TAH under GA at 48 h.