Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study.

BACKGROUND: Central nervous system (CNS) has a different immune surveillance system; therefore, fever at admission and timeline of fever response after antitubercular treatment (ATT) may follow a different course in CNS infection. We report the predictors of fever response in tuberculous meningitis (TBM) including the effect of tumour necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs). METHODS: Fifty-seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF-α gene in PBMCs was quantified by real-time polymerase chain reaction and TNF-α concentration in CSF by cytokine bead array both in the patients and 14 matched controls. RESULTS: All the patients had history of fever for a median duration of 75 days. The admission temperature ranged between 37.2°C and 40°C and correlated with CSF cell counts (p < 0.05). Cranial MRI was abnormal in 54 (94.7%) and revealed exudates in 33(57.9%), hydrocephalus in 27(47.4%), infarction in 27(47.4%) and tuberculoma in 33(57.9%) patients. Fever subsided after a median duration of 18 (2 60) days of treatment. Twelve (21.8%) patients only became afebrile within 10 days. The expression of TNF-α gene correlated with CSF concentration of TNF-α (p = 0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00-1.04; p = 0.01). CONCLUSION: In the patients with TBM, defervescence takes longer time, and TNF-α gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF-α-modifying drugs in TBM.

NMR based CSF metabolomics in tuberculous meningitis: correlation with clinical and MRI findings.

We report the potential role of 1H Nuclear Magnetic Resonance (NMR) based metabolomics in tuberculous meningitis (TBM). We also correlate the significant metabolites with clinical-radiological parameters. Forty-three patients with TBM were included, and their severity of meningitis was graded as stages I to III, and patients with positive Mycobacterium tuberculosis or its nucleic acid was considered as definite TBM. 1H NMR-based metabolomic study was performed on (CSF) samples, and the significant metabolites compared to healthy controls were identified. Outcome at three months was defined as death, poor and good based on the modified Rankin Scale. These metabolites were compared between definite and probable groups of TBM, and also correlated with MRI findings. About 11 metabolites were found to be significant for distinguishing TBM from the controls. In TBM, lactate, glutamate, alanine, arginine, 2-hydroxyisobutyrate, formate, and cis-aconitate were upregulated, and glucose, fructose, glutamine, and myo-inositol were downregulated compared to the controls. For differentiating TBM from the controls, the AUC of the ROC curve generated using these significant metabolites was 0.99, with a 95% confidence interval from 0.96 to 1, demonstrating that these metabolites were able to classify cases with good sensitivity and specificity. Lactate concentration in CSF correlated with hemoglobin, CSF glucose, and infarction. The outcome did not correlate with metabolomics parameters. NMR-based CSF metabolomics have a potential role in differentiating TBM from the controls.

Optimising working space for laparoscopic pyeloplasty in infants: Preliminary observations with the SGPGI Protocol.

AIMS: This study aimed to test the efficacy of SGPGI protocol to minimise bowel distension and optimise working space for laparoscopic pyeloplasty in infants. METHODOLOGY: All infants who underwent laparoscopic pyeloplasty for unilateral pelvi-ureteric junction obstruction (PUJO) between January 2017 and March 2020 were included in the study. The patient cohort was divided into two groups: Group A and B. Group A included patients who underwent routine pre-operative preparation. Group B included patients wherein the SGPGI protocol was used. The key features of the protocol were fasting for 8 h, enemas, inserting a nasogastric tube in the pre-operative period and decompressing the colon on the operation table. Demographic features, pre-operative, intraoperative and post-operative parameters were compared between the two groups. RESULTS: A total of 26 infants with unilateral PUJO underwent laparoscopic pyeloplasty during the study period. Group A included 12 patients and Group B included 14 patients. Both the groups were similar in age, weight and sex distribution. The median surgeon's rating score for suturing conditions was 2 for Group A and 5 for Group B patients (P > 0.05). The operating time was significantly longer in Group A (196 ± 21 min) as compared to Group B (114 ± 18 min) (P < 0.05). In Group A, intra-abdominal pressure (IAP) varied between 9 and 14 mmHg (median 12 mmHg), while in Group B, IAP varied between 6 and 9 mmHg (median 8 mmHg) (P < 0.05). In Group A, in 2/12 cases (16.7%), conversion to an open procedure was necessary because of inadequate working space owing to gross intestinal distension. Two patients in Group A also had intraoperative injuries to adjacent structures due to poor working space. CONCLUSIONS: Optimal working space is critical to the performance of advanced laparoscopic surgery like pyeloplasty in infants. SGPGI protocol significantly improves working space, which permits a faster and safer surgery with a lower intra-abdominal working pressure. This protocol is simple, safe and easy to replicate at most centres in our country.

Evaluating the Efficacy and Safety of the Existing Repurposed Pharmacological Agents for Treating COVID-19: A Meta-analysis and Systematic Review of Clinical Trials.

PURPOSE: The present study systematically searched important medical databases, assessed the quality of available pieces of evidence, and performed a meta-analysis to test the efficacy of different therapeutic options currently available for treating COVID-19. MATERIALS AND METHODS: PubMed, CNKI, LILACS, Koreamed, WHO clinical trial registry, and medRxiv were searched since December 2019. Any observational or controlled study that tested the efficacy of any pharmacological intervention in COVID-19 patients either prospectively or retrospectively was included in the qualitative analysis. We assessed outcomes as dichotomous variables, i.e., a patient having a positive clinical outcome. Relative risks/risk ratios (RR) having a 95% confidence interval (CI) were derived. Studies conforming to inclusion criteria were pooled using the random-effect model. RESULTS: Nine trials on hydroxychloroquine (HCQ), six studies on antiviral, four studies on monoclonal antibodies, two on corticosteroids, two on convalescent plasma (CP), and one on interferon-α2b were included in the systematic review. Meta-analysis containing six scientific trials and analyzing 522 patients revealed that the relative risk of positive clinical outcomes with HCQ treatment was 1.042 (95% CI, 0.884 to 1.874) with a number needed to treat (NNT) of 12.6. A meta-analysis of two studies analyzing 285 patients showed that the relative risk of clinical resolution with lopinavir and ritonavir combination was 1.152 (95% CI 0.709 to 1.87). Out of various antiviral used, the only remdesivir showed a positive result in a case series. Monoclonal antibodies showed decreased C-reactive protein, decreased oxygen, and ventilator requirements. A corticosteroid may increase mortality with increased dose. Two small case series on CP showed some promising results. CONCLUSION: The study showed slightly favorable results with HCQ, monoclonal antibodies, remdesivir, and CP in treating COVID-19 patients. Further research is warranted in establishing the efficacy of studied interventions. PROSPERO IDENTIFIER: CRD42020180979. HOW TO CITE THIS ARTICLE: Choupoo NS, Das SK, Haldar R, Sarkar H, Tewari R, Ray S. Evaluating the Efficacy and Safety of the Existing Repurposed Pharmacological Agents for Treating COVID-19: A Meta-analysis and Systematic Review of Clinical Trials. Indian J Crit Care Med 2020;24(11):1106-1113.

Dynamic magnetic resonance imaging parameters for objective assessment of the magnitude of tethered cord syndrome in patients with spinal dysraphism.

BACKGROUND: Dynamic magnetic resonance imaging (MRI)-based criteria for diagnosing magnitude of tethered cord syndrome (TCS) in occult spinal dysraphism are proposed. METHODS: In this prospective, case-control design study, MRI lumbosacral spine was performed in 51 subjects [pilot group (n = 10) without TCS (for defining radiological parameters), control group (n = 10) without TCS (for baseline assessment), and study group (n = 31) with spinal dysraphism (thick filum terminale [n = 12], lumbar/lumbosacral meningomyelocoele [n = 6], and lipomyelomeningocoele [n = 13])]. The parameters compared in control and study groups included oscillatory frequency (OF), difference in ratio, in supine/prone position, of distance between posterior margin of vertebral body and anterior margin of spinal cord (oscillatory distance [OD]), with canal diameter, at the level of conus as well as superior border of contiguous two vertebrae above that level; delta bending angle (ΔBA), difference, in supine/prone position, of angle between longitudinal axis of conus and that of lower spinal cord; and sagittal and axial root angles, subtended between exiting ventral nerve roots and longitudinal axis of cord. An outcome assessment at follow-up was also done. RESULTS: In the study group (cord tethered), significantly less movement at the level of conus (OF0, p = 0.013) and one level above (OF1, p = 0.03) and significant difference in ΔBA (p = 0.0) were observed in supine and prone positions, compared to controls. Ventral nerve root stretching resulted in sagittal/axial root angle changes. Median OF (0.04) in the lipomyelomeningocoele group was significantly less than that in control group (0.23). Median OF was also lesser in patients with thick filum terminale or meningomyelocele. Difference in median sagittal and axial root angles among the study and control groups was statistically significant (p = 0.00). CONCLUSION: New dynamic MRI-based parameters to establish the presence and magnitude of TCS have been defined. OF measured the extent of loss of translational cord displacement in supine and prone positions; ΔBA defined the relative angulation of conus with lower spinal cord, and sagittal and axial root angles represented ventral nerve root stretching. The difference in OF or ΔBA was minimum in the group with thick filum terminale and progressively increased in the groups with lipomyelomeningocele and meningomyelocele.

Xylometazoline nasal drops induced anaphylaxis: An atypical perioperative complication.

Xylometazoline nasal drops used for nasal decongestion can have side-effect in the form of palpitation, hypertension, headache, and tremors. Anaphylaxis to xylometazoline nasal drops is a relatively unrecognized complication. We encountered a patient posted for tonsillectomy who developed serious anaphylaxis upon administration of a commercially available preparation of xylometazoline nasal drops and required aggressive management for stabilization. Further evaluation and literature search indicated toward the preservative (benzylalkonium chloride) as the cause of this adverse event.

Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

Intravenous Lignocaine to Blunt Extubation Responses: A Double-Edged Sword.

Extubation after general anesthetic procedures is often accompanied by transient undesirable responses such as hypertension, tachycardia, coughing, bucking, and raised intracranial and intraocular pressures. In neurosurgical procedures, they need to be stringently controlled to prevent the rise in cerebral blood flow, increase in intracranial pressure, and intracranial bleeding. Intravenous (IV) lignocaine (1-1.5 mg/kg) administration is one such method to blunt extubation responses. We describe a case where IV lignocaine was administered within the recommended doses to inhibit the extubation response, but the same resulted in generalized convulsions because of the clinical and physiological status of the patient at that point of time. Intravenous lignocaine administered to obtund extubation responses can itself manifest in toxic reactions depending on the preexisting clinical and physiological state of the patients. Thus, extreme caution and vigilance is to be maintained whenever IV local anesthetics are used for such purposes.

Paediatric Intravenous Splint: A Cause of Pressure Injury during Neurosurgery in Prone Position.

Splint application avoids unwanted movement of limbs and kinking of intravenous catheters in infants, allowing free flow of intravenous fluids. However, if placed in contact with dependent surfaces during prone surgeries, they have the propensity to cause inadvertent pressure injuries. This occurs due to the weight of the limb and continuous friction and is augmented by a rise in the local temperature and perspiration. We wish to share our experience of such an unintentional injury caused by a paediatric intravenous splint.

Valsalva maneuver: Its implications in clinical neurosurgery.

Valsalva maneuver is associated with diverse physiological changes. These changes are used in various diagnostic and therapeutic clinical settings. Valsalva maneuver is also employed during various phases of neurosurgical procedures to achieve specific targets and confirm intraoperative findings. In this article, we attempt to describe the various clinical applications of the Valsalva maneuver within the realms of clinical neurosurgery. The associated complications of this act have also been discussed.

Contemporary social network sites: Relevance in anesthesiology teaching, training, and research.

OBJECTIVE: The phenomenal popularity of social networking sites has been used globally by medical professionals to boost professional associations and scientific developments. They have tremendous potential to forge professional liaisons, generate employment,upgrading skills and publicizing scientific achievements. We highlight the role of social networking mediums in influencing teaching, training and research in anaesthesiology. BACKGROUND: The growth of social networking sites have been prompted by the limitations of previous facilities in terms of ease of data and interface sharing and the amalgamation of audio visual aids on common platforms in the newer facilities. REVIEW: Contemporary social networking sites like Facebook, Twitter, Tumblr,Linkedn etc and their respective features based on anaesthesiology training or practice have been discussed. A host of advantages which these sites confer are also discussed. Likewise the potential pitfalls and drawbacks of these facilities have also been addressed. CONCLUSION: Social networking sites have immense potential for development of training and research in Anaesthesiology. However responsible and cautious utilization is advocated.

Nitroglycerine, esmolol and dexmedetomidine for induced hypotension during functional endoscopic sinus surgery: A comparative evaluation.

BACKGROUND AND AIM: Induced hypotension limits intra-operative blood loss to provide better visibility of the surgical field and diminishes the incidence of major complications during functional endoscopic sinus surgery (FESS). We aimed at comparing nitroglycerine, esmolol and dexmedetomidine for inducing controlled hypotension in patients undergoing FESS. MATERIAL AND METHODS: One hundred and fifty American Society of Anesthesiologists physical status I or II adult patients undergoing FESS under general anesthesia were randomly allocated to three groups of 50 patients each. Group E received esmolol in a loading and maintenance dose of 1 mg/kg over 1 min and 0.5-1.0 mg/kg/h, respectively. Group D received a loading dose of dexmedetomidine 1 µg/kg over 10 min followed by an infusion 0.5-1.0 µg/kg/h, and group N received nitroglycerine infusion at a dose of 0.5-2 µg/kg/min so as to maintain mean arterial pressure (MAP) between 60 and 70 mmHg in all the groups. The visibility of the surgical field was assessed by surgeon using Fromme and Boezaart scoring system. Hemodynamic variables, total intra-operative fentanyl consumption, emergence time and time to first analgesic request were recorded. Any side-effects were noted. The postoperative sedation was assessed using Ramsay Sedation Score. RESULT: The desired MAP (60-70 mmHg) could be achieved in all the three study groups albeit with titration of study drugs during intra-operative period. No significant intergroup difference was observed in Fromme's score during the intra-operative period. The mean total dose of fentanyl (µg/kg) used was found to be significantly lower in group D compared to groups E and N (1.2 ± 0.75 vs. 3.6 ± 1.3 and 2.9 ± 1.1 respectively). The mean heart rate was significantly lower in group D compared to groups E and N at all times of measurement (P < 0.05). The MAP was found to be significantly lower in group D compared to groups E and N after infusion of study drugs, after induction, just after intubation and 5 min after intubation (P < 0.05). The Ramsay Sedation Scores were significantly higher in group D (score 3 in 46%) when compared to group E (score 2 in 50%) and group N (score 2 in 54%) (P < 0.001). The emergence time was significantly lower in group E and group N compared to group D. Time to first analgesic request was significantly longer in group D. CONCLUSION: Dexmedetomidine and esmolol provided better hemodynamic stability and operative field visibility compared to nitroglycerin during FESS. Dexmedetomidine provides an additional benefit of reducing the analgesic requirements and providing postoperative sedation.

Transtracheal ultrasound for verification of endotracheal tube placement: a systematic review and meta-analysis.

PURPOSE: Early confirmation of endotracheal tube placement is of paramount importance to prevent hypoxia and its catastrophic consequences. Despite certain limitations, capnography is considered the gold standard to evaluate the proper placement of an endotracheal tube. Ultrasound is a novel tool with some definitive advantages over capnography. It enables a real-time view and can be performed quickly; furthermore, it is independent of pulmonary blood flow and does not require lung ventilation. In this review, we aimed to evaluate the diagnostic accuracy of transtracheal ultrasound in detecting endotracheal intubation. SOURCE: We completed an extensive search of MEDLINE®, EMBASE™, The Cochrane Library, KoreaMed, LILACS, OpenGrey, and the World Health Organization International Clinical Trials Registry from their inception to September 4, 2014. The studies that met the inclusion criteria were pooled and a meta-analysis was conducted. PRINCIPAL FINDINGS: Eleven studies and 969 intubations were included in the final analysis. Eight studies and 713 intubations were performed in emergency situations and the others were carried out in elective situations. Transtracheal ultrasonography's pooled sensitivity and specificity with 95% confidence intervals (CIs) were 0.98 (95% CI 0.97 to 0.99) and 0.98 (95% CI 0.95 to 0.99), respectively. In emergency scenarios, transtracheal ultrasonography showed an aggregate sensitivity and specificity of 0.98 (95% CI 0.97 to 0.99) and 0.94 (95% CI 0.86 to 0.98), respectively. CONCLUSION: Transtracheal ultrasound is a useful tool to confirm endotracheal intubation with an acceptable degree of sensitivity and specificity. It can be used in emergency situations as a preliminary test before final confirmation by capnography.

Nasocardiac reflex during aspiration and injection through a nasogastric tube: An infrequent occurrence.

Nasocardiac reflex is a relatively less discussed variant of trigeminovagal reflex where the afferent arc of the reflex is represented by any of the branches of the trigeminal nerves, and the efferent arc is via the vagus nerve. Elicitation of this reflex is commonly seen during surgical manipulation and is manifested as bradycardia or even asystole. We report a case where nasocardiac reflex was unusually observed in a patient when aspiration and injection were done through a nasogastric tube.

Comparison between intranasal dexmedetomidine and intranasal ketamine as premedication for procedural sedation in children undergoing MRI: a double-blind, randomized, placebo-controlled trial.

INTRODUCTION: Providing anesthesia to children undergoing MRI is challenging. Adequate premedication, administered noninvasively, would make the process smoother. In this study, we compare the efficacy of intranasal dexmedetomidine (DXM) with the intranasal administration of ketamine for procedural sedation in children undergoing MRI. METHODS: We studied 150 children, between 1 and 10 years of age, divided randomly into three groups (DXM, K, and S). For blinding, every child received the intranasal drugs twice; syringe S1, 60 min before, and syringe S2, 30 min before intravenous (IV) cannulation. For children in group DXM, S1 contained DXM (1 µg/kg) and S2 was plain saline. Children in group K received saline in S1 and ketamine (5 mg/kg) in S2 whereas children in group S received saline in both S1 and S2. The child's response to drug administration, ease of IV cannulation, the satisfaction of the anesthesiologist and child's parents with the premedication, and the total propofol dose required for the satisfactory conduct of the procedure were compared. We also compared the time to awakening and discharge of the child as well as the occurrence of any side effects with these drugs. RESULTS: Both DXM and ketamine were equally effective as premedication in these patients. Most of the children accepted the intranasal drugs with minimal discomfort; 90.4 % of the anesthesiologists in the DXM group and 82.7 % in the ketamine group were satisfied with the conditions for IV cannulation whereas only 21.3 % were satisfied in the saline group. The total dose of propofol used was less in the study groups. Furthermore, children in group DXM and group K had earlier awakening and discharge than those in group S. CONCLUSION: DXM and ketamine were equally effective, by the intranasal route, as premedication in children undergoing MRI.

mRNA profiling of cytokines to understand paradoxical response in HIV-uninfected tuberculous meningitis.

Paradoxical reaction (PR) in tuberculous meningitis (TBM) is a major management issue. We report mRNA profiling of cytokines to understand PR in HIV-uninfected TBM patients. 72 patients with TBM were included, and their clinical, MRI, and mRNA profiling of tumor necrosis factor (TNF) α, interleukin (IL) 6, IL10 and interferon (IFN) γ genes in the peripheral blood mononuclear cells were done at admission and 6 weeks of antitubercular treatment. Cytokine profiling was done using reverse transcriptase polymerase chain reaction. PR was defined if repeat MRI at 6 weeks revealed new or increase in exudates, tuberculoma, hydrocephalus or infarctions. Outcome was defined at 6 months using modified Rankin Scale (mRS), and categorized as death, poor and good. 44 (61.1 %) patients had PR, and 28 (38.9 %) had paradoxical tuberculoma (PT). The expression of IL6 and TNFα genes were higher in PR and PT groups. Stage of meningitis and hydrocephalus at admission predicted PR. Patients with PR and PT had more frequently poor outcome. About three-fifth HIV-uninfected TBM patients have PR and two-fifth have PT. Paradoxical reaction is associated with higher expression of IL6 and TNFα. Patients with severe meningitis with hydrocephalus develop PR more frequently.