The Urban-Rural Divide in Neurocritical Care in Low-Income and Middle-Income Countries.

The term "urban-rural divide" encompasses several dimensions and has remained an important concern for any country. The economic disparity; lack of infrastructure; dearth of medical specialists; limited opportunities to education, training, and health care; lower level of sanitation; and isolating effect of geographical location deepens this gap, especially in low-income and middle-income countries (LMICs). This article gives an overview of the rural-urban differences in terms of facilities related to neurocritical care (NCC) in LMICs. Issues related to common clinical conditions such as stroke, traumatic brain injury, myasthenia gravis, epilepsy, tubercular meningitis, and tracheostomy are also discussed. To facilitate delivery of NCC in resource-limited settings, proposed strategies include strengthening preventive measures, focusing on basics, having a multidisciplinary approach, promoting training and education, and conducting cost-effective research and collaborative efforts. The rural areas of LMICs bear the maximum impact because of their limited access to preventive health services, high incidence of acquired brain injury, inability to have timely management of neurological emergencies, and scarcity of specialist services in a resource-deprived health center. An increase in the health budget allocation for rural areas, NCC education and training of the workforce, and provision of telemedicine services for rapid diagnosis, management, and neurorehabilitation are some of the steps that can be quite helpful.

Comparison of Glasgow Coma Scale Full Outline of UnResponsiveness and Glasgow Coma Scale: Pupils Score for Predicting Outcome in Patients with Traumatic Brain Injury.

Background: Glasgow coma scale (GCS) score is the most widely used clinical score for the initial assessment of neurologically injured patients and is also frequently used for prognostication. Other scores such as the Full Outline of UnResponsivness (FOUR) score and the Glasgow Coma Scale-Pupils (GCS-P) score have been more recently developed and are gaining popularity. This prospective cohort study was conducted to compare various scores in terms of their ability to predict outcomes at 3 months in patients with traumatic brain injury (TBI). Materials and methods: The study was carried out between October 2020 and March 2022. Patients who presented to the hospital with TBI were assessed for inclusion. Initial coma scores were assessed in the emergency department and again after 48 hours of admission. Outcome was assessed using the extended Glasgow outcome score (GOSE) at 3 months after injury. The receiver operating curve (ROC) was plotted to correlate coma scores with the outcome, and the area under the curve (AUC) was compared. Results: A total of 355 patients with TBI were assessed for eligibility, of which 204 patients were included in the study. The AUC values to predict poor outcomes for initial GCS, FOUR, and GCS-P scores were 0.75 each. The AUC values for 48-hour coma scores were 0.88, 0.87, and 0.88, respectively. Conclusion: The GCS, FOUR, and GCS-P scores were found to be comparable in predicting the functional outcome at 3 months as assessed by GOSE. However, coma scores assessed at 48 hours were better predictors of poor outcomes at 3 months than coma scores recorded initially at the time of hospital admission. How to cite this article: Chawnchhim AL, Mahajan C, Kapoor I, Sinha TP, Prabhakar H, Chaturvedi A. Comparison of Glasgow Coma Scale Full Outline of UnResponsiveness and Glasgow Coma Scale: Pupils Score for Predicting Outcome in Patients with Traumatic Brain Injury. Indian J Crit Care Med 2024;28(3):256-264.

Evaluation of the GCS-Pupils Score for PrOgnosis in trauMatic brAin injury- The COMA Study.

OBJECTIVES: Glasgow Coma Scale-Pupils (GCS-P) score has been found to be strongly related to in-hospital mortality in retrospective studies. We hypothesized that GCS-P would be better prognosticator than Glasgow Coma Scale (GCS) in patients with traumatic brain injury (TBI). METHODS: In this prospective, multicentric, observational study, GCS and GCS-P scores were noted in adult TBI patients at ICU admission. Demographic variables, relevant clinical history, clinical/radiological findings and ICU complications were also noted. Extended Glasgow Outcome scale was noted at hospital discharge and at 6 months post-injury. Logistic regression analysis was carried out to estimate the odds for poor outcome adjusted for covariates. Sensitivity, specificity, area under curve (AUC) and odds ratio are reported for poor outcome at estimated cutoff point. RESULTS: A total of 573 patients were included in this study. The predictive power for mortality, shown by the AUC, was 0.81 [95% CI: 0.77-0.85] for GCS and 0.81 [95% CI: 0.77-0.86] for GCS-P score, both being comparable. Similarly, the predictive ability for outcome at discharge and 6 months, the AUC-ROC for both GCS and GCS-P were comparable. CONCLUSIONS: GCS-P is a good predictor of mortality and poor outcome. However, the predictive performance of GCS and GCS-P for in-hospital mortality and functional outcome at discharge and at 6 months remains comparable.

Endocrine Dysfunction After Traumatic Brain Injury: An Ignored Clinical Syndrome?

Traumatic brain injury (TBI) incurs substantial health and economic burden, as it is the leading reason for death and disability globally. Endocrine abnormalities are no longer considered a rare complication of TBI. The reported prevalence is variable across studies, depending on the time frame of injury, time and type of testing, and variability in hormonal values considered normal across different studies. The present review reports evidence on the endocrine dysfunction that can occur after TBI. Several aspects, including the pathophysiological mechanisms, clinical consequences/challenges (in the acute and chronic phases), screening and diagnostic workup, principles of therapeutic management, and insights on future directions/research agenda, are presented. The management of hypopituitarism following TBI involves hormonal replacement therapy. It is essential for health care providers to be aware of this complication because at times, symptoms may be subtle and may be mistaken to be caused by brain injury itself. There is a need for stronger evidence for establishing recommendations for optimum management so that they can be incorporated as standard of care in TBI management.

A National Survey on Coma Epidemiology, Evaluation, and Therapy in India: Revisiting the Curing Coma Campaign Come Together Survey.

BACKGROUND: The limited representation from developing countries in the original COME TOGETHER survey gave us an impetus to conduct this survey in the Indian subcontinent. METHODS: This cross-sectional online survey was conducted from August through September 2022. Participants were health care physicians caring for patients with coma and disorders of consciousness. Fischer's exact test or the Mann-Whitney U-test was used to compare respondents who agreed or disagreed with the preestablished coma definition. Fleiss κ values were calculated to assess agreement among respondents. A p value less than 0.05 was considered statistically significant. RESULTS: The survey was completed by 130 physicians. We found substantial interrater agreement on absence of wakefulness (71.54%; κ = 0.71), Glasgow Coma Score ≤ 8 (78.46%; κ = 0.78), and failure to respond purposefully to visual, verbal, or tactile stimuli (66.15%; κ = 0.66). Reported common etiologies of coma included traumatic brain injury (50.76%), ischemic stroke (30%), and intracerebral hemorrhage (29.23%). The most common clinical assessment tools used for coma included the Glasgow Coma Score (92.3%) and neurological examination (60.8%). Neurological examination was the most common diagnostic tool used (100%), followed by magnetic resonance imaging (89.2%), basic laboratory studies (88.5%), and head computed tomography/angiography (86.9%). Pharmacological interventions used to stimulate arousal in patients with coma were sedation vacation (91.5%), electrolyte/endocrine correction (65.4%), osmotic therapy with mannitol (60%), hypertonic saline (54.6%), modafinil (46.9%), and antidote for drugs (45.4%). Among the nonpharmacological interventions, sensory stimulation (57.7%) was the most commonly used modality. The most common discharge disposition for comatose patients who survived hospitalization were home with or without services (70.0%). CONCLUSIONS: Differences from the global survey were noted regarding the following: traumatic brain injury being the most common etiology of coma in India, more frequent practice of sedation interruption, less frequent use of electroencephalography in India, rare use of pharmacological neurostimulants, and home being the most common discharge disposition in India.

Augmenting Hypertensive Therapy in Patients with Postoperative Subarachnoid Hemorrhage: What's the Right Choice?

How to cite this article: Prabhakar H. Augmenting Hypertensive Therapy in Patients with Postoperative Subarachnoid Hemorrhage: What's the Right Choice? Indian J Crit Care Med 2023;27(4):233-234.

Can Bispectral Index be a Point-of-care Monitor for Sleep Quality Assessment in Critically Ill Patients?

How to cite this article: Kapoor I, Prabhakar H. Can Bispectral Index be a Point-of-care Monitor for Sleep Quality Assessment in Critically Ill Patients? Indian J Crit Care Med 2023;27(11):782-783.

Readiness of the Stroke Treatment in India: Still an Uphill Task!

How to cite this article: Singhal V, Prabhakar H. Readiness of the Stroke Treatment in India: Still an Uphill Task! Indian J Crit Care Med 2023;27(9):607-608.

Rate of Multidrug-resistance to Antimicrobial Drugs in Patients in Pediatric Neurointensive Care.

Background: Multidrug-resistant (MDR) organisms in the critical care unit are a worldwide concern. The vulnerability to MDR infection in pediatric patients admitted in neurocritical care are due to altered mental status, immature immune system, higher risk of aspiration, and more frequent use of invasive devices. We aimed to measure the burden of MDR infection in pediatric neurosurgical intensive care unit (NSICU) patients. Methods: All pediatric patients between 1 and 18 years for intracranial and spine surgeries admitted for more than 48 hours in NSICU were enrolled in the study. If patients showed a clinical picture of pneumonia, bloodstream infection (BSI), or urinary tract infection (UTI) after receiving mechanical ventilation or an indwelling device for at least 48 hours, samples of tracheal aspirates, urine, blood, and cerebrospinal fluid (CSF) were sent for microbiological culture. We noted the type of organism, MDR infection rate, and associated risk factors. Pearson Chi-squared test and Fisher's test were used for statistical analysis; p < 0.05 was considered statistically significant. Results: A total of 274 pediatric patients were studied. In 1 year, there was a total of 1,790 patient days. The inclusive MDR infection rate was 17.3/1,000 patient days. Also, Klebsiella pneumoniae (38.7%) was the commonest MDR pathogen. The commonest source of infection was BSI (32.3%). The risk factors associated with MDR infections were the length of stay in NSICU, mechanical ventilation of more than 5 days, emergency surgery, respiratory and cardiac comorbidities, and poor nutrition status (p < 0.05). Conclusion: The MDR infection rate in our study was 17.3/1,000 patient days in pediatric patients. Also, K. pneumonia e was found to be the commonest MDR pathogen. Bloodstream was the commonest source of infection. How to cite this article: Patel S, Prabhakar H, Kapoor I. Rate of Multidrug-resistance to Antimicrobial Drugs in Patients in Pediatric Neurointensive Care. Indian J Crit Care Med 2023;27(1):67-72.

Comparison between Transcranial Sonography and Computerized Tomography Scans to Assess the Midline Shift in Patients with Traumatic Brain Injury.

Background: Midline shift (MLS) of the brain is an important clinical finding diagnosed on computed tomography (CT) imaging and transcranial sonography (TCS) can help diagnose MLS at the bedside and facilitate interventions to improve outcomes. The study aimed to find an association between TCS- and CT-based assessments of MLS in patients with traumatic brain injury (TBI). Patients and methods: We included all adult patients with moderate-to-severe TBI of either gender, aged between 18 and 65 years, undergoing intracranial surgery under general anesthesia over a period of 3 months. Consciousness was assessed with the help of the Glasgow coma scale (GCS) and Glasgow coma scale-pupillary (GCS-P) score. We calculated MLS using a CT scan and TCS. Bland Altman graph along with Pearson's and Spearman's coefficient tests was used. Results: A total of 17 patients were analyzed in this study. The MLS was 0.52 ± 0.90 cm using TCS and 0.58 ± 0.39 cm using CT scan. The Pearson's correlation coefficient (r 2) of the difference between MLS measured by TCS and CT imaging was 0.002 (p < 0.05). Conclusion: Transcranial sonography could detect MLS in patients with TBI, provided a minimum time window is used between MLS measurements by TCS and CT scan. How to cite this article: Kapoor I, Pandit S, Prabhakar H, Mahajan C. Comparison between Transcranial Sonography and Computerized Tomography Scans to Assess the Midline Shift in Patients with Traumatic Brain Injury. Indian J Crit Care Med 2023;27(1):64-66.

The Curing Coma Campaign®: Concerns in the Indian Subcontinent.

Background: The Curing Coma Campaign (CCC) was launched by the Neurocritical Care Society (NCS) in 2019, with the purpose to bring together a diverse group of coma scientists, neurointensivists, and neurorehabilitationists. Methods: The aim of this campaign is to move beyond the limitations imposed by current definitions of coma and identify mechanisms to improve prognostication, identify test therapies, and impact outcomes. At the moment, whole approach of the CCC appears ambitiously challenging. Results: This could be true only for the Western world, such as the North America, Europe, and few developed countries. However, the whole concept of CCC may face potential challenges in the lower-middle income countries. India has several stumbling blocks that need to and can be addressed in the future, for a meaningful outcome, as envisaged in the CCC. Conclusion: India has several potential challenges, which we aim to discuss in this article. How to cite this article: Kapoor I, Mahajan C, Zirpe KG, Samavedam S, Sahoo TK, Sapra H, et al. The Curing Coma Campaign®: Concerns in the Indian Subcontinent. Indian J Crit Care Med 2023;27(2):89-92.

A Nationwide Survey on the Practice of End-of-life Care Issues in Critical Care Units in India.

Background: End-of-life (EOL) care is the care of terminally ill patients who are nearing their end. It includes important components like palliative care, supportive care, hospice care, patient's right to choose, and choice of medical intervention, including continuation of routine medical interventions. The aim of this survey was to assess the practices of EOL care in various critical care units in India. Methods: The participants included clinicians involved in EOL care of patients with advanced diseases in different hospital across India. We sent blast emails and posted links on social media for inviting participants to take the survey. Study data were collected and managed by using Google Forms. The collected information was automatically entered into a spread sheet and stored in a secure database. Results: In total, 91 clinicians took the survey. The years of experience, practice area, and setting had significant effect on the palliative care, terminal strategy, and prognostication in terminally ill patients (p < 0.05). Statistical analysis was done using software STATA. Descriptive statistics were performed, and results were presented as number (percentage). Conclusion: The years of work experience, the practice area, and the practice setting have a strong impact on EOL care management of terminally ill patients. There are a lot of gaps in providing EOL care for these patients. Many reforms are needed in the Indian health care system to make EOL care better. How to cite this article: Kapoor I, Prabhakar H, Mahajan C, Zirpe KG, Tripathy S, Wanchoo J, et al. A Nationwide Survey on the Practice of End-of-life Care Issues in Critical Care Units in India. Indian J Crit Care Med 2023;27(5):305-314.

The Menace of Meningitis!

How to cite this article: Prabhakar H. The Menace of Meningitis! Indian J Crit Care Med 2022;26(12):1231-1232.

Paravertebral anaesthesia with or without sedation versus general anaesthesia for women undergoing breast cancer surgery.

BACKGROUND: Breast cancer is one of the most common cancers among women. Surgical removal of the cancer is the mainstay of treatment; however, tumour handling during surgery can cause microscopic dissemination of tumour cells and disease recurrence. The body's hormonal response to surgery (stress response) and general anaesthesia may suppress immunity, promoting tumour dissemination. Paravertebral anaesthesia numbs the site of surgery, provides good analgesia, and blunts the stress response, minimising the need for general anaesthesia. OBJECTIVES: To assess the effects of paravertebral anaesthesia with or without sedation compared to general anaesthesia in women undergoing breast cancer surgery, with important outcomes of quality of recovery, postoperative pain at rest, and mortality. SEARCH METHODS: On 6 April 2020, we searched the Specialised Register of the Cochrane Breast Cancer Group (CBCG); CENTRAL (latest issue), in the Cochrane Library; MEDLINE (via OvidSP); Embase (via OvidSP); the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal; and ClinicalTrials.gov for all prospectively registered and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted in adult women undergoing breast cancer surgery in which paravertebral anaesthesia with or without sedation was compared to general anaesthesia. We did not include studies in which paravertebral anaesthesia was given as an adjunct to general anaesthesia and then this was compared to use of general anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted details of trial methods and outcome data from eligible trials. When data could be pooled, analyses were performed on an intention-to-treat basis, and the random-effects model was used if there was heterogeneity. When data could not be pooled, the synthesis without meta-analysis (SWiM) approach was applied. The GRADE approach was used to assess the certainty of evidence for each outcome. MAIN RESULTS: Nine studies (614 participants) were included in the review. All were RCTs of parallel design, wherein female patients aged > 18 years underwent breast cancer surgery under paravertebral anaesthesia or general anaesthesia. None of the studies assessed quality of recovery in the first three postoperative days using a validated questionnaire; most assessed factors affecting quality of recovery such as postoperative analgesic use, postoperative nausea and vomiting (PONV), hospital stay, ambulation, and patient satisfaction. Paravertebral anaesthesia may reduce the 24-hour postoperative analgesic requirement (odds ratio (OR) 0.07, 95% confidence interval (CI) 0.01 to 0.34; 5 studies, 305 participants; low-certainty evidence) compared to general anaesthesia. Heterogeneity (I² = 70%) was attributed to the fixed dose of opioids and non-steroidal analgesics administered postoperatively in one study (70 participants), masking a difference in analgesic requirements between groups. Paravertebral anaesthesia probably reduces the incidence of PONV (OR 0.16, 95% CI 0.08 to 0.30; 6 studies, 324 participants; moderate-certainty evidence), probably results in a shorter hospital stay (mean difference (MD) -79.39 minutes, 95% CI -107.38 to -51.40; 3 studies, 174 participants; moderate-certainty evidence), and probably reduces time to ambulation compared to general anaesthesia (SWiM analysis): percentages indicate vote counting based on direction of effect (100%, 95% CI 51.01% to 100%; P = 0.125; 4 studies, 375 participants; moderate-certainty evidence). Paravertebral anaesthesia probably results in higher patient satisfaction (MD 5.52 points, 95% CI 1.30 to 9.75; 3 studies, 129 participants; moderate-certainty evidence) on a 0 to 100 scale 24 hours postoperatively compared to general anaesthesia. Postoperative pain at rest and on movement was assessed at 2, 6, and 24 postoperative hours on a 0 to 10 visual analogue scale (VAS). Four studies (224 participants) found that paravertebral anaesthesia as compared to general anaesthesia probably reduced pain at 2 postoperative hours (MD -2.95, 95% CI -3.37 to -2.54; moderate-certainty evidence). Five studies (324 participants) found that paravertebral anaesthesia may reduce pain at rest at 6 hours postoperatively (MD -1.54, 95% CI -3.20 to 0.11; low-certainty evidence). Five studies (278 participants) found that paravertebral anaesthesia may reduce pain at rest at 24 hours postoperatively (MD -1.19, 95% CI -2.27 to -0.10; low-certainty evidence). Differences in the methods of two studies (119 participants) and addition of clonidine to the local anaesthetic in two studies (109 participants), respectively, contributed to the heterogeneity (I² = 96%) observed for these two outcomes. Two studies (130 participants) found that paravertebral anaesthesia may reduce pain on movement at 6 hours (MD-2.57, 95% CI -3.97 to -1.17) and at 24 hours (MD -2.12, 95% CI -4.80 to 0.55; low-certainty evidence). Heterogeneity (I² = 96%) was observed for both outcomes and could be due to methodological differences between studies. None of the studies reported mortality related to the anaesthetic technique. Eight studies (574 participants) evaluated adverse outcomes with paravertebral anaesthesia: epidural spread (0.7%), minor bleeding (1.4%), pleural puncture not associated with pneumothorax (0.3%), and Horner's syndrome (7.1%). These complications were self-limiting and resolved without treatment. No data are available on disease-free survival, chronic pain, and quality of life. Blinding of personnel or participants was not possible in any study, as a regional anaesthetic technique was compared to general anaesthesia. Risk of bias was judged to be serious, as seven studies had concerns of selection bias and three of detection bias. AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that paravertebral anaesthesia probably reduces PONV, hospital stay, postoperative pain (at 2 hours), and time to ambulation and results in greater patient satisfaction on the first postoperative day compared to general anaesthesia. Paravertebral anaesthesia may also reduce postoperative analgesic use and postoperative pain at 6 and 24 hours at rest and on movement based on low-certainty evidence. However, RCTs using validated questionnaires are needed to confirm these results. Adverse events observed with paravertebral anaesthesia are rare.

Prognostic Value of Serially Estimated Serum Procalcitonin Levels in Traumatic Brain Injury Patients With or Without Extra Cranial Injury on Early In-hospital Mortality: A Longitudinal Observational Study.

BACKGROUND: Traumatic brain injury (TBI) is associated with majority of trauma deaths, and objective tools are required to understand the severity of injury. The application of a biomarker like procalcitonin (PCT) in TBI may allow for assessment of severity and thus aid in prognostication and correlation with mortality and outcome. AIMS: The primary objective is to determine the correlation between PCT concentrations with TBI outcomes (mainly in terms of mortality) at intensive care unit (ICU)/hospital discharge. Secondary objectives are to evaluate correlation with associated extra cranial injuries and complications during hospital stay. METHODS: In total, 186 TBI patients aged > 18 years with minimum survival for at least 12 h admitted to the ICU at the level 1 trauma center were prospectively included in the study and divided into two groups: TBI with and without extra cranial injuries. All admitted patients were treated according to the standard institutional protocol. The PCT levels were obtained on admission, on day 2, and 5. Clinical, laboratory, diagnostic, and therapeutic data were also collected. Primary mortality is defined as death related to central nervous system (CNS) injury, while secondary mortality defined as death related to sepsis or extracranial cause. RESULTS: Median PCT levels at admission, day 2, and day 5 in TBI patients with extracranial injuries were 3.0, 0.83, and 0.69 ng/ml. In total, primary mortality was observed in 18 (9.7%) patients, while secondary causes were attributable in 20 (12.3%) patients. Regression analysis for primarily CNS cause of mortality showed PCT cutoff level at admission more than 5.5 ng/ml carried sensitivity and specificity of 75%, but for secondary cause (sepsis) of mortality, PCT cutoff values on day 2 > 1.15 ng/ml were derived significant with sensitivity of 70% and specificity of 66%. No significant association of parameters like length of ICU stay, Glasgow outcome scale (GOS), and primary/secondary mortality with the presence of extracranial injuries in TBI patients as compared with TBI alone was noted. CONCLUSION: This observational study demonstrates the poor correlation between PCT concentrations with outcome at days 1, 2, and 5 post-injury. The predicted relationship between PCT levels and outcome was not confirmed, and that these results do not support the prognostic utility of PCT biomarker in this population for outcome (mortality) assessment in TBI patients with or without extracranial injuries.

Twenty-one Days of Solitude.

As the world is now gradually coming out of the "lockdown" phase, one can expect a change in the demographics and epidemiology of trauma. With traffic back on roads and shifting life again towards "normalcy", it is imperative to carry out introspection and see how we can stop trauma from reaching its pre-COVID levels. How to cite this article: Prabhakar H. Twenty-one Days of Solitude. Indian J Crit Care Med 2021;25(3):249-250.

Phenytoin Sodium and Acetate-Maleate Buffered Balanced Salt Solutions are Physically Incompatible!

How to cite this article: Mahajan C, Singh BP, Kapoor I, Prabhakar H. Phenytoin Sodium and Acetate-Maleate Buffered Balanced Salt Solutions are Physically Incompatible! Indian J Crit Care Med 2021;25(3):352.

Consensus Statement on Analgo-sedation in Neurocritical Care and Review of Literature.

AIM AND OBJECTIVE: Our main objective in developing this consensus is to bring together a set of most agreed-upon statements from a panel of global experts that would act as a guide for clinicians working in neurocritical care units (NCCUs). BACKGROUND: Given the physiological benefits of analgo-sedation in the NCCU, there is little information on their tailoring in the NCCU. This lack of evidence and guidelines on the use of sedation and analgesia in patients with neurological injury leads to a variation in clinical care based on patient requirements and institutional protocols. REVIEW RESULTS: Thirty-nine international experts agreed to be a member of this consensus panel. A Delphi method based on a Web-based questionnaire developed with Google Forms on a secure institute server was used to seek opinions of experts. Questions were related to sedation and analgesia in the neurocritical care unit. A predefined threshold of agreement was established as 70% to support any recommendation, strong, moderate, or weak. No recommendations were made below this threshold. Responses were collected from all the experts, summated, and expressed as percentage (%). After three rounds, consensus could be reached for 6 statements related to analgesia and 5 statements related to sedation. Consensus could not be reached for 10 statements related to analgesia and 5 statements related to sedation. CONCLUSION: This global consensus statement may help in guiding practitioners in clinical decision-making regarding analgo-sedation in the NCCUs, thereby helping in improving patient recovery profiles. CLINICAL SIGNIFICANCE: In the lack of high-level evidence, the recommendations may be seen as the current best clinical practice. HOW TO CITE THIS ARTICLE: Prabhakar H, Tripathy S, Gupta N, Singhal V, Mahajan C, Kapoor I, et al. Consensus Statement on Analgo-sedation in Neurocritical Care and Review of Literature. Indian J Crit Care Med 2021;25(2):126-133.

Effect of Percutaneous Tracheostomy on Optic Nerve Sheath Diameter [TONS Trial].

BACKGROUND: Elective percutaneous tracheostomy [PCT] is the widely performed procedure in neurocritically ill patients as an airway management choice in neurocritical care unit [NICU]. Intracranial pressure [ICP] is a vital parameter to be monitored in these patients while undergoing any surgical procedure including PCT. Optic nerve sheath diameter [ONSD], being a surrogate of ICP, can be done bedside and carries less complications than invasive ICP monitoring. The aim of our study was to assess the effect of PCT on ONSD at different stages of PCT. MATERIALS AND METHODS: A total of 158 patients with various intracranial pathologies scheduled for PCT in NICU were screened for eligibility in our study. We assessed mean values of ONSD, HR, MBP, and SpO2 for changes over various time points during PCT using generalized estimating equation (GEE). A p value of <0.05 was considered significant. RESULTS: A total of 135 patients who underwent PCT were analyzed for the study. The values of ONSD changed significantly at different stages of PCT procedure compared to baseline. The baseline ONSD value was 0.39 ± 0.05 cm. ONSD rose significantly to 0.40 ± 0.06 cm during positioning, 0.41 ± 0.06 cm during skin incision, 0.42 ± 0.07 cm during dilatation of tract, 0.41 ± 0.07 cm during insertion of tracheostomy, and 0.41 ± 0.06 cm at the end of the procedure. CONCLUSIONS: PCT leads to a significant rise of ONSD values during all stages of PCT. The available evidences point toward detrimental rise in ICP during PCT. ICP can be monitored noninvasively by measuring ONSD using bedside ultrasound. HOW TO CITE THIS ARTICLE: Kapoor I, Wanchoo J, Mahajan C, Singhal V, Roy H, Kumar S, et al. Effect of Percutaneous Tracheostomy on Optic Nerve Sheath Diameter [TONS Trial]. Indian J Crit Care Med 2021;25(4):382-387.

Rufinamide add-on therapy for drug-resistant epilepsy.

BACKGROUND: Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical activity in the brain. Despite the development of more than 10 new antiepileptic drugs (AEDs) since the early 2000s, approximately a third of people with epilepsy remain resistant to pharmacotherapy, often requiring treatment with a combination of AEDs. In this review, we summarised the current evidence regarding rufinamide, a novel anticonvulsant medication, which, as a triazole derivative, is structurally unrelated to any other currently used anticonvulsant medication when used as an add-on treatment for drug-resistant epilepsy. In January 2009, rufinamide was approved by the US Food and Drug Administration for the treatment of children four years of age and older with Lennox-Gastaut syndrome. It is also approved as an add-on treatment for adults and adolescents with focal seizures. This is an updated version of the original Cochrane Review published in 2018. OBJECTIVES: To evaluate the efficacy and tolerability of rufinamide when used as an add-on treatment for people with drug-resistant epilepsy. SEARCH METHODS: We imposed no language restrictions. We contacted the manufacturers of rufinamide and authors in the field to identify any relevant unpublished studies. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled, add-on trials of rufinamide, recruiting people (of any age or gender) with drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: 50% or greater reduction in seizure frequency (primary outcome); seizure freedom; treatment withdrawal; and adverse effects (secondary outcomes). Primary analyses were intention-to-treat (ITT) and we presented summary risk ratios (RRs) with 95% confidence intervals (CIs). We evaluated dose response in regression models. We carried out a risk of bias assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach. MAIN RESULTS: The review included six trials, representing 1759 participants. Four trials (1563 participants) included people with uncontrolled focal seizures. Two trials (196 participants) included individuals with established Lennox-Gastaut syndrome. Overall, the age of adults ranged from 18 to 80 years and the age of children ranged from 4 to 16 years. Baseline phases ranged from 28 to 56 days and double-blind phases from 84 to 96 days. Five of the six included trials described adequate methods of concealment of randomisation, and only three described adequate blinding. All analyses were by ITT. Overall, five studies were at low risk of bias and one had unclear risk of bias due to lack of reported information around study design. All trials were sponsored by the manufacturer of rufinamide and therefore were at high risk of funding bias. The overall RR for 50% or greater reduction in seizure frequency was 1.79 (95% CI 1.44 to 2.22; 6 randomised controlled trials (RCTs), 1759 participants; moderate-certainty evidence), indicating that rufinamide (plus conventional AED) was significantly more effective than placebo (plus conventional AED) in reducing seizure frequency by at least 50% when added to conventionally used AEDs in people with drug-resistant focal epilepsy. Data from only one study (73 participants) reported seizure freedom: RR 1.32 (95% CI 0.36 to 4.86; 1 RCT, 73 participants; moderate-certainty evidence). The overall RR for treatment withdrawal (for any reason and due to AED) was 1.83 (95% CI 1.45 to 2.31; 6 RCTs, 1759 participants; moderate-certainty evidence), showing that rufinamide was significantly more likely to be withdrawn than placebo. Most adverse effects were significantly more likely to occur in the rufinamide-treated group. Adverse events significantly associated with rufinamide were headache, dizziness, somnolence, vomiting, nausea, fatigue, and diplopia. The RRs for these adverse effects were as follows: headache 1.36 (95% Cl 1.08 to 1.69; 3 RCTs, 1228 participants; high-certainty evidence); dizziness 2.52 (95% Cl 1.90 to 3.34; 3 RCTs, 1295 participants; moderate-certainty evidence); somnolence 1.94 (95% Cl 1.44 to 2.61; 6 RCTs, 1759 participants; moderate-certainty evidence); vomiting 2.95 (95% Cl 1.80 to 4.82; 4 RCTs, 777 participants; low-certainty evidence); nausea 1.87 (95% Cl 1.33 to 2.64; 3 RCTs, 1295 participants; moderate-certainty evidence); fatigue 1.46 (95% Cl 1.08 to 1.97; 3 RCTs, 1295 participants; moderate-certainty evidence); and diplopia 4.60 (95% Cl 2.53 to 8.38; 3 RCTs, 1295 participants; low-certainty evidence). There was no important heterogeneity between studies for any outcomes. Overall, we assessed the evidence as moderate to low certainty due to wide CIs and potential risk of bias from some studies contributing to the analysis. AUTHORS' CONCLUSIONS: For people with drug-resistant focal epilepsy, rufinamide when used as an add-on treatment was effective in reducing seizure frequency. However, the trials reviewed were of relatively short duration and provided no evidence for long-term use of rufinamide. In the short term, rufinamide as an add-on was associated with several adverse events. This review focused on the use of rufinamide in drug-resistant focal epilepsy, and the results cannot be generalised to add-on treatment for generalised epilepsies. Likewise, no inference can be made about the effects of rufinamide when used as monotherapy.