Handling injectable medications in anaesthesia: Guidelines from the Association of Anaesthetists.

Peri-operative medication safety is complex. Avoidance of medication errors is both system- and practitioner-based, and many departments within the hospital contribute to safe and effective systems. For the individual anaesthetist, drawing up, labelling and then the correct administration of medications are key components in a patient's peri-operative journey. These guidelines aim to provide pragmatic safety steps for the practitioner and other individuals within the operative environment, as well as short- to long-term goals for development of a collaborative approach to reducing errors. The aim is that they will be used as a basis for instilling good practice.

Substance use disorder in the anaesthetist: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists.

Anaesthetists have a higher incidence of substance use disorder when compared with other doctors. This might be due to the ease of access to intravenous opioids, propofol, midazolam, inhalational agents and other anaesthetic drugs. Alcohol use disorder continues to be the most common problem. Unfortunately, the first sign that something is amiss might be the anaesthetist's death from an accidental or deliberate overdose. While there are few accurate data, suicide is presumed to be the cause of death in approximately 6-10% of all anaesthetists. If we are to prevent this, substance use disorder must be recognised early, we should ensure the anaesthetist is supported by their department and hospital management and that the anaesthetist engages fully with treatment. Over 75% of anaesthetists return to full practice if they co-operate fully with the required treatment and supervision.

A Study of Catecholamine Levels in Acute ICH Patients and its Clinical Significance.

ICH is one of the most serious neurological emergency which can result in high mortality which may be related to catecholamine release. We aim to evaluate serum catecholamine levels in acute ICH and correlate their levels with clinical parameters of stress and outcome. MATERIAL: Consecutive patients with CT proven ICH within 7 days of ictus were included and their clinical finding, SIRS Parameters, GCS, NIH score, laboratory parameters (ESR, CRP) were evaluated. Serum Catecholamine (DA, NE, E) levels were measured by LCMS. The patients were followed up at discharge and one month, the outcome was defined by mortality and 1 month modified Rankin scale (good 0-2, poor >2). OBSERVATION: There were 31 patients of acute ICH. Patients were admitted 1 to 2 days after ictus. Among the patients 19 were male and 12 were female.Their age ranged from 31 to 86 with mean 53.3+- 16.7. History of hypertension was present in 27.3% of patients. Their average GCS was median 12 (6.0, 15.0) and NIHSS was 12.5 (8.5, 22) Their average ESR was 30 (13,56) and average CRP was 1.8 (1.1, 5.9). Almost all pateints had raised SIRS parameters. There was an increase in levels of Dopamine (63.2 pg/ml), Epinephrine (73.5 pg/ml) and Norepinephrine (390pg/ml) on admission as compared to their levels 1 week after ictus or on discharge (Dopamine 35.6, Epinephrine 52.1, and Norepinephrine 241 pg/ml). CONCLUSION: CA surge is common in ICH pateints and it correlates with severity and outcome of patient. 6 pateints died in the hospital 72 % of patients had poor outcome. Catecholamine levels were higher in poor outcome patients.

Airway management guidance for the endemic phase of COVID-19.

It is now apparent that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) will remain endemic for some time. Improved therapeutics and a vaccine may shorten this period, but both are far from certain. Plans must be put in place on the assumption that the virus and its disease will continue to affect the care of patients and the safety of staff. This will impact particularly on airway management due to the inherent risk to staff during such procedures. Research is needed to clarify the nature and risk of respiratory aerosol-generating procedures. Improved knowledge of the dynamics of SARS-CoV-2 infection and immunity is also required. In the meantime, we describe the current status of airway management during the endemic phase of the COVID-19 pandemic. Some controversies remain unresolved, but the safety of patients and staff remains paramount. Current evidence does not support or necessitate dramatic changes to choices for anaesthetic airway management. Theatre efficiency and training issues are a challenge that must be addressed, and new information may enable this.

Impaired Autophagy Flux is Associated with Proinflammatory Microglia Activation Following Japanese Encephalitis Virus Infection.

Role of autophagy in Japanese encephalitis viral (JEV) infection is not well known. In the present study, we reported the role of autophagy flux in microglia activation, neurobehavioral function and neuronal death using a mouse model of JEV. Markers for autophagy (LC3-II/I, SQSTM1/P62, phos-Akt, phos-AMPK), and neuronal death (cleaved caspase 12, H2Ax, polyubiquitin) were investigated by western blot at 1, 3 and 7 days post inoculation. Cathepsin D was measured in cerebral cotex of JEV infected mice spectrophotometrically. Microglia activation and pro-inflammatory cytokines (IL1ß, TNF-α, IFNγ, IL6) were measured by immunohistochemistry, western blot and qPCR analysis. In order to determine the neuroinflammatory changes and autophagy mediated neuronal cell death, BV2-microglia and N2a-neuronal cells were used. Autophagy activation marker LC3-II/I and its substrate SQSTM1/P62 were significantly increased while cathepsin D activity was decreased on day 7 post inoculation in cerebral cortex. Microglia in cortex were activated and showed higher expression of proinflammatory mRNA of IL1ß, TNF-α, IFNγ and IL6, with increased DNA damage (H2AX) and neuronal cell death pathways in hippocampus and neurobehavioral dysfunction. Similar observations on JEV infection mediated autophagy flux inhibition and neuronal cell death was found in N2a neuronal cell. Collectively, our study provides evidence on the role of autophagy regulation, microglial activation and neurodegeneration following JEV infection.

Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK.

These guidelines aim to ensure that patients with adrenal insufficiency are identified and adequately supplemented with glucocorticoids during the peri-operative period. There are two major categories of adrenal insufficiency. Primary adrenal insufficiency is due to diseases of the adrenal gland (failure of the hormone-producing gland), and secondary adrenal insufficiency is due to deficient adrenocorticotropin hormone secretion by the pituitary gland, or deficient corticotropin-releasing hormone secretion by the hypothalamus (failure of the regulatory centres). Patients taking physiological replacement doses of corticosteroids for either primary or secondary adrenal insufficiency are at significant risk of adrenal crisis and must be given stress doses of hydrocortisone during the peri-operative period. Many more patients other than those with adrenal and hypothalamic-pituitary causes of adrenal failure are receiving glucocorticoids as treatment for other medical conditions. Daily doses of prednisolone of 5 mg or greater in adults and 10-15 mg.m-2 hydrocortisone equivalent or greater in children may result in hypothalamo-pituitary-adrenal axis suppression if administered for 1 month or more by oral, inhaled, intranasal, intra-articular or topical routes; this chronic administration of glucocorticoids is the most common cause of secondary adrenal suppression, sometimes referred to as tertiary adrenal insufficiency. A pragmatic approach to adrenal replacement during major stress is required; considering the evidence available, blanket recommendations would not be appropriate, and it is essential for the clinician to remember that adrenal replacement dosing following surgical stress or illness is in addition to usual steroid treatment. Patients with previously undiagnosed adrenal insufficiency sometimes present for the first time following the stress of surgery. Anaesthetists must be familiar with the symptoms and signs of acute adrenal insufficiency so that inadequate supplementation or undiagnosed adrenal insufficiency can be detected and treated promptly. Delays may prove fatal.

Possible role of transforming growth factor ß in tuberculous meningitis.

BACKGROUND: Transforming growth factor ß (TGF-ß) is an anti-inflammatory cytokine and its role in hydrocephalus and stoke has been suggested. Tuberculous meningitis (TBM) is associated with exudates, stroke, hydrocephalus and tuberculoma, but the role of TGF-ß has not been evaluated in relation to these changes. AIM: To evaluate the cerebrospinal fluid (CSF) TGF-ß level in the patients with TBM, and correlate these with clinical findings, MRI changes, paradoxical response and outcome at 6months. METHODS: TBM patients diagnosed on the basis of clinical, CSF and MRI criteria were prospectively included. The clinical details including duration of illness, seizures, focal motor deficit, Glasgow Coma Scale (GCS) score and stage of TBM were noted. Presence of exudate, hydrocephalus, tuberculoma and infarction in MRI was also noted. MRI was repeated at 3months and presence of paradoxical response was noted. Cerebrospinal fluid TGF-ß was measured using ELISA on admission and repeated at 3months and these were compared with 20 controls. RESULTS: TGF-ß level was significantly higher in TBM compared to the controls (385.76±249.98Vs 177.85±29.03pg/ml, P<0.0001). TGF-ß correlated with motor deficit, infarction and tuberculoma on admission but did not correlate with CSF abnormalities, drug induced hepatitis, paradoxical response and outcome. TGF-ß level at 3months was significantly lower than the baseline but remained higher than the controls. CONCLUSION: CSF TGF-ß levels are elevated in TBM and correlate with infarction and tuberculoma.

Spectrum of hyperosmolar hyperglycaemic state in neurology practice.

BACKGROUND & OBJECTIVES: Hyperosmolar hyperglycaemic state (HHS) is a medical emergency, but there is a paucity of studies reporting the spectrum of neurological manifestations of HHS. We, therefore, report the neurological spectrum, triggering factors and outcome of HHS in general neurology practice. METHODS: The records of the patients with HHS were extracted from computerized hospital information system and those managed currently were prospectively included. The demographic, clinical manifestations, duration of diabetes and precipitating events such as infection, stress and stroke were noted. Patients with HHS were categorized into seizure, movement disorder and encephalopathy groups. Their electroencephalography, magnetic resonance imaging (MRI) findings and outcome were noted. RESULTS: There were 17 patients with HHS (age range 40 and 75 yr) and seven were females. Seven patients were diabetic for five years, one for four years, one for one year and four were diagnosed after the occurrence of HHS. Four patients had epilepsia partialis continua persisting for 72-360 h, one patient had focal seizures and his MRI revealed T2 hyperintensity in frontal region in one patient and cerebellar vermian hyperintensity in another. All the five patients improved, but two had neurological deficits on discharge. Nine patients had encephalopathy which was precipitated by stroke in six patients, urinary infections in two and meningitis in one. Three females had hemichorea-hemiballismus syndrome, which was triggered by infections. Abnormal movements lasted 5-10 days and responded to correction of hyperosmolarity. Nine out of 17 patients improved completely whereas the remaining eight had partial recovery, these patients had stroke, ventilator-related complications or meningoencephalitis. INTERPRETATION & CONCLUSIONS: The most common presentation of HHS was encephalopathy (9) followed by seizure (5) and hemichorea-hemiballismus syndrome (3) which responded to the correction of hyperosmolar state.

Is VEGF a marker of severity of scrub typhus infection?

Vascular endothelial growth factor (VEGF) and its receptors have been reported as severity markers of septicemia. Scrub typhus (ST) results in multi-organ dysfunction but the role of VEGF has not been evaluated. We report VEGF and its receptors in ST and its correlation with severity, outcome and laboratory findings. Thirty patients with ST diagnosed by solid phase immune chromatographic assay and Weil-Felix tests were included. Their clinical details, Glasgow Coma Scale (GCS), SOFA and modified Rankin Scale (mRS) scores and laboratory findings were noted. VEGF, VEGFR1 and VEGFR2 were done by ELISA at admission and repeated at 1 month. Outcome was defined at 1 month. Serum VEGF and VEGF-R1 levels were significantly higher and VEGFR2 was significantly lower in the ST patients compared to the controls. These levels significantly improved at 1 month. VEGF level correlated with SOFA score (p = 0.05) and SGPT (p = 0.04). VEGFR1 correlated with hemoglobin (p = 0.04), platelet count (p = 0.03), serum CK (p = 0.001), weakness (p = 0.04) and mRS score (p = 0.04). VEGFR2 did not correlate with any clinical or laboratory parameters. All the patients recovered with doxycycline. Serum VEGF and VEGFR1 levels increased in ST and suggest disease severity but do not predict outcome.

Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India.

BACKGROUND & OBJECTIVES: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. METHODS: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. RESULTS: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. INTERPRETATION & CONCLUSIONS: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

Recommendations for standards of monitoring during anaesthesia and recovery 2015: Association of Anaesthetists of Great Britain and Ireland.

This guideline updates and replaces the 4th edition of the AAGBI Standards of Monitoring published in 2007. The aim of this document is to provide guidance on the minimum standards for physiological monitoring of any patient undergoing anaesthesia or sedation under the care of an anaesthetist. The recommendations are primarily aimed at anaesthetists practising in the United Kingdom and Ireland. Minimum standards for monitoring patients during anaesthesia and in the recovery phase are included. There is also guidance on monitoring patients undergoing sedation and also during transfer of anaesthetised or sedated patients. There are new sections discussing the role of monitoring depth of anaesthesia, neuromuscular blockade and cardiac output. The indications for end-tidal carbon dioxide monitoring have been updated.

VEGF and its receptors in dengue virus infection.

Vascular permeability determines the severity of dengue virus infection. Vascular endothelial growth factor (VEGF) and its (receptor 1) R1 and (receptor 2) R2 receptors may provide insight about the neurological complications of dengue. We report VEGF and its R1 and R2 receptors level in dengue patients and correlate these with neurological complications. Consecutive patients with dengue were subjected to clinical and neurological evaluations. Their blood counts, serum chemistry, including liver and kidney function tests, serum creatine kinase (CK), and albumin were measured. VEGF, VEGFR1 and VEGFR2 were measured by ELISA in the patients and 16 matched controls. Twenty four patients with dengue were included whose ages ranged between 15 and 67 years, and nine of whom were females. Serum VEGF level was insignificantly lower in dengue patients whereas VEGFR1 was significantly higher (P = 0.01) and VEGFR2 was significantly lower (P = 0.005) compared to controls. VEGFR2 correlated with systolic blood pressure, coagulopathy, and serum CK levels. None of the other clinical and biochemical parameters correlated with VEGF and VEGFR1 levels. VEGFR1 and R2 normalized at 1 month. VEGFR2 correlates with the clinical severity of dengue and muscle dysfunction.

Neurological manifestations of scrub typhus.

OBJECTIVE: To evaluate the neurological manifestations of scrub typhus and correlate their clinical, EEG and MRI findings. METHODS: A cross-sectional study over 2 years included patients with scrub typhus diagnosed by solid phase immunochromatographic assay or Weil-Felix test. A detailed clinical evaluation including Glasgow Coma Scale (GCS) was documented. Blood counts, chemistry, ECG, chest radiograph, cerebrospinal fluid (CSF), EEG and cranial MRI were performed. Outcome on discharge and at 1 month were categorised into good and poor based on modified Rankin Scale. RESULTS: Thirty-seven patients with ages ranging between 3 and 71 years were included; 51% of whom were females. All patients had fever and myalgia. Thirty-one (84%) patients had impaired consciousness, and six were deeply comatose (GCS score ≤8). Eight patients presented with status epilepticus. MRI revealed meningeal enhancement in only 1/25 (4%) patient and EEG showed generalised slowing in 6/28 (21.4%). Among 31 patients with altered sensorium, CSF studies were conducted on 28. Nineteen patients had meningoencephalitis and 9 encephalopathy, but no significant differences were observed in clinical, laboratory, EEG and MRI findings. All patients responded within 48 h to doxycycline and had good recovery at 1 month. Patients with low GCS score had significantly more focal neurological deficit (r=0.5; p=0.002), longer hospital stay (r=-0.4; p=0.03) and more disability on discharge (r=-0.4; p=0.01). CONCLUSIONS: Meningoencephalitis/encephalopathy may be seen in two-third of patients with scrub typhus. Scrub typhus should be included in the differential diagnosis of febrile encephalopathy.

Peri-operative management of the obese surgical patient 2015: Association of Anaesthetists of Great Britain and Ireland Society for Obesity and Bariatric Anaesthesia.

Guidelines are presented for the organisational and clinical peri-operative management of anaesthesia and surgery for patients who are obese, along with a summary of the problems that obesity may cause peri-operatively. The advice presented is based on previously published advice, clinical studies and expert opinion.

Safety and efficacy of levofloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial.

OBJECTIVES: We report the efficacy and safety of levofloxacin versus rifampicin in tuberculous meningitis (TBM). PATIENTS AND METHODS: In this open-label, randomized controlled trial from India, patients with TBM diagnosed on the basis of clinical, MRI and CSF findings were included. Patients with hepatic or renal dysfunction, organ transplantation, malignancy, pregnancy, lactation, allergy, seizure, age <15 years and antitubercular treatment ≥1 month were excluded. Sixty patients each were randomized to levofloxacin (10 mg/kg, maximum 500 mg) or rifampicin (10 mg/kg, maximum 450 mg). They also received isoniazid, pyrazinamide, ethambutol, prednisolone and aspirin. The primary outcome was death and secondary outcome measures were 6 month disability, repeat MRI changes and serious adverse events (SAEs). RESULTS: The median age of the patients was 34.5 (16-75) years. The baseline clinical and MRI findings were similar between the two groups. At 6 months, 13 out of 60 (21.7%) patients in the levofloxacin arm and 23 out of 60 (38.3%) patients in the rifampicin arm had died (P = 0.07). On Cox regression analysis, survival in the levofloxacin group was significantly better than in the rifampicin group (hazard ratio 2.13, 95% CI 1.04-4.34, P = 0.04). The functional outcome (P = 0.47) was, however, not significantly different between the two groups. On intention-to-treat analysis, 10 out of 47 (21.3%) in the levofloxacin arm and 5 out of 37 (13.5%) in the rifampicin arm had poor recovery. Repeat MRI findings did not differ between the groups. Levofloxacin was discontinued more frequently than rifampicin due to SAEs (16 versus 4, P = 0.01). CONCLUSIONS: Levofloxacin is superior to rifampicin in reducing 6 month death in TBM but not disability. Levofloxacin may be used in TBM especially in those patients with hepatotoxicity and without seizure.

Predictors of outcome of myasthenic crisis.

There is paucity of study on predictors of myasthenic crisis (MC), prolonged ventilation and their outcome, a reason why this study was undertaken. Sixty-four patients with myasthenia gravis (MG) were included whose median age was 45 (6-84) years. Their clinical treatment, presence of thymoma, anti-acetylcholine receptor antibody (AchRAb), thymectomy, comorbidities, offending drugs and occurrence of MC were noted. Patients needing prolonged ventilation (>15 days) were noted. Hospital mortality, MG quality of life (QOL) at discharge and thereafter annual hospital visit, admission, expenditure and work day loss were enquired. Fourteen (21.9 %) patients had MC within 1-120 (median 8.5) months of disease onset within a median follow-up of 48 (3-264) months. The precipitating factors were infection in six, surgery in five, tapering of drugs in two and reaction to iodinated contrast in one patient. Male gender, bulbar weakness, AchRAb, thymoma, surgery and comorbid illnesses were related to MC. Eight of them (57.1 %) needed prolonged ventilation. Half the patients with MC had recurrent crisis (2-4 attacks). Death was not related to MC although MC patients had worse QOL, higher annual treatment expenditure with frequent hospital visit and hospitalization. In conclusion, association of comorbid illness with MC and prolonged ventilation highlights the need of close follow-up and appropriate management.

Beware of parotitis induced by iodine-containing contrast media.

Carotid stenting is being increasingly used for revascularization of the moderate to severe carotid stenosis and thus its complications are increasingly being recognized. We report a rare complication of induced by iodine contrast in a patient undergoing carotid stenting. s. A 51 year old man after the second stenting developed multiple small infarcts in spite of the distal device. He also had painful parotid swelling which improved within a week. One should be aware of iodine parotitis s in the patients undergoing iodinated contrast study.

Stimulus-sensitive myoclonus and cerebellar ataxia following chikungunya meningoencephalitis.

Chikungunya virus was initially thought to be a non-neurotropic virus, but recently neurological complications have been reported in patients with chikungunya virus infection. Here, we report a rare case of stimulus-sensitive myoclonus following chikungunya meningoencephalitis. The cranial MRI scan of the patient was normal, the cerebrospinal fluid contained 200 lymphocytes/mm(3), and the serum immunoglobulin M ELISA was positive for chikungunya. The patient improved completely after 1 month of treatment. This case study illustrates that chikungunya virus should also be considered in a febrile patient with myoclonus, especially in an endemic area.

Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial.

OBJECTIVE: This study compares efficacy and safety of divalproate extended release (DVA-ER) and amitriptyline (AMT) in migraine. MATERIALS AND METHODS: Three hundred migraineurs having >4 attacks monthly were randomized into DVA-ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events. RESULTS: The median age was 32 years, and 241 were women. 150 patients each received DVA-ER and AMT. At 3 months, 74.7% in DVA-ER and 62% patients in AMT group improved in headache frequency (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA-ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA-ER group. CONCLUSION: Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis.

Low molecular weight heparin versus unfractionated heparin in cerebral venous sinus thrombosis: a randomized controlled trial.

BACKGROUND: There is no randomized controlled trial (RCT) evaluating the efficacy and safety of low molecular weight heparin (LMWH) compared to unfractionated heparin (UFH) in cerebral venous sinus thrombosis (CVST). In this RCT, we have evaluated the efficacy and safety of LMWH versus UFH in CVST. METHODS: Consecutive patients with CVST diagnosed on the basis of MR venography (MRV) who was free of bleeding diathesis, malignancy, hepatic or renal failure were prospectively enrolled. History, clinical findings and risk factors were evaluated. MRI and MRV findings were recorded. The patients were randomized to LMWH and UFH groups for 14 days followed by oral anticoagulant. The hospital mortality and 3 months outcome as assessed by Barthel index (BI) score were noted. RESULTS: 32 patients received UFH and 34 received LMWH. The baseline demographic, clinical and radiological parameters were similar in both the groups. Six patients died and all were in UFH group (P = 0.01). At 3 months, insignificantly higher number of patients recovered completely in LMWH compared to UFH group (30 vs. 20). There was no serious side effect needing withdrawal of drugs except one was withdrawn from UFH because of heparin-induced thrombosis. CONCLUSION: Low molecular weight heparin resulted in significantly lower hospital mortality in CVST compared to UFH.