Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains).

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial. Design setting and participants: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home. Results and conclusions: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

Impact of COVID-19 on non-COVID intensive care unit service utilization, case mix and outcomes: A registry-based analysis from India.

Background: Coronavirus disease 2019 (COVID-19) has been responsible for over 3.4 million deaths globally and over 25 million cases in India. As part of the response, India imposed a nation-wide lockdown and prioritized COVID-19 care in hospitals and intensive care units (ICUs). Leveraging data from the Indian Registry of IntenSive care, we sought to understand the impact of the COVID-19 pandemic on critical care service utilization, case-mix, and clinical outcomes in non-COVID ICUs.  Methods: We included all consecutive patients admitted between 1 st October 2019 and 27 th September 2020. Data were extracted from the registry database and included patients admitted to the non-COVID or general ICUs at each of the sites. Outcomes included measures of resource-availability, utilisation, case-mix, acuity, and demand for ICU beds. We used a Mann-Whitney test to compare the pre-pandemic period (October 2019 - February 2020) to the pandemic period (March-September 2020). In addition, we also compared the period of intense lockdown (March-May 31 st 2020) with the pre-pandemic period. Results: There were 3424 patient encounters in the pre-pandemic period and 3524 encounters in the pandemic period. Comparing these periods, weekly admissions declined (median [Q1 Q3] 160 [145,168] to 113 [98.5,134]; p=0.00002); unit turnover declined (median [Q1 Q3] 12.1 [11.32,13] to 8.58 [7.24,10], p<0.00001), and APACHE II score increased (median [Q1 Q3] 19 [19,20] to 21 [20,22] ; p<0.00001). Unadjusted ICU mortality increased (9.3% to 11.7%, p=0.01519) and the length of ICU stay was similar (median [Q1 Q3] 2.11 [2, 2] vs. 2.24 [2, 3] days; p=0.15096). Conclusion: Our registry-based analysis of the impact of COVID-19 on non-COVID critical care demonstrates significant disruptions to healthcare utilization during the pandemic and an increase in the severity of illness.

Variation in therapeutic strategies for the management of severe COVID-19 in India: A nationwide cross-sectional survey.

AIM: During the pandemic of coronavirus disease 2019 (COVID-19), the physicians are using various off-label therapeutics to manage COVID-19. We undertook a cross-sectional survey to study the current variation in therapeutic strategies for managing severe COVID-19 in India. METHODS: From January 4 to January 18, 2021, an online cross-sectional survey was conducted among physicians involved in the management of severe COVID-19. The survey had three sections: 1. Antiviral agents, 2. Immunomodulators, and 3. Adjuvant therapies. RESULTS: 1055 respondents (from 24 states and five union territories), of which 64.2% were consultants, 54.3% working in private hospitals, and 39.1% were from critical care medicine completed the survey. Remdesivir (95.2%), antithrombotics (94.2%), corticosteroids (90.3%), vitamins (89.7%) and empirical antibiotics (85.6%) were the commonly used therapeutics. Ivermectin (33%), convalescent plasma (28.6%) and favipiravir (17.6%) were other antiviral agents used. Methylprednisolone (50.2%) and dexamethasone (44.1%) were preferred corticosteroids and at a dose equivalent of 8 mg of dexamethasone phosphate (70.2%). There was significant variation among physicians from different medical specialities in the use of favipiravir, corticosteroids, empirical antibiotics and vitamins. CONCLUSION: There is a considerable variation in the physicians' choice of therapeutic strategies for the management of severe COVID-19 in India, as compared with the available evidence.

Macrolevel association of COVID-19 with non-communicable disease risk factors in India.

BACKGROUND & AIMS: Greater COVID-19 related mortality has been reported among persons with various non-communicable diseases (NCDs). We performed an ecological study to determine the association of state-level cases and deaths with NCD risk factors and healthcare and social indices. METHODS: We obtained cumulative national and state-level data on COVID-19 cases and deaths from publicly available database www.covid19india.org from February to end November 2020. To identify association with major NCD risk factors, NCDs, healthcare related and social variables we obtained data from public sources. Association was determined using univariate and multivariate statistics. RESULTS: More than 9.5 million COVID-19 cases and 135,000 deaths have been reported in India towards end of November 2020. There is significant positive correlation (Pearson r) of state-level COVID-19 cases and deaths per million, respectively, with NCD risk factors- obesity (0.64, 0.52), hypertension (0.28, 0.16), diabetes (0.66, 0.46), NCD epidemiological transition index (0.58, 0.54) and ischemic heart disease mortality (0.22, 0.33). Correlation is also observed with indices of healthcare access and quality (0.71, 0.61), urbanization (0.75, 0.73) and human (0.61, 0.56) and sociodemographic (0.70, 0.69) development. Multivariate adjusted analyses shows strong correlation of COVID-19 burden and deaths with NCD risk factors (r2 = 0.51, 0.43), NCDs (r2 = 0.32, 0.16) and healthcare (r2 = 0.52, 0.38). CONCLUSIONS: COVID-19 disease burden and mortality in India is ecologically associated with greater state-level burden of NCDs and risk factors, especially obesity and diabetes.

Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research.

Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%.  Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research.

Effect of intramucosal infiltration of different concentrations of adrenaline on hemodynamics during transsphenoidal surgery.

BACKGROUND AND AIMS: Neurosurgeons routinely instill vasopressors, with or without local anesthetics, to prepare nasal passages prior to transsphenoidal surgeries. As there is a paucity of data comparing the effect of intramucosal nasal infiltration of different concentrations of adrenaline that is, 1:200,000 and 1:400,000 in patients undergoing transsphenoidal surgery, we conducted this study to evaluate the effect of these two concentrations of adrenaline with 2% lignocaine on hemodynamics as well as bleeding. MATERIALS AND METHODS: Fifty-two American Society of Anesthesiologists I/II patients, aged 15-70 years, undergoing transsphenoidal surgery for pituitary or sellar masses were enrolled. Prior to surgical incision, nasal septal mucosa was infiltrated with lignocaine-adrenaline solution, after randomly allocating them to one of the two groups, with patients in Group A receiving intramucosal infiltration using 2% lignocaine with 1:200,000 adrenaline and those in Group B receiving 2% lignocaine with 1:400,000 adrenaline. Following infiltration, hemodynamic parameters were recorded every 1 min for 5 min and thereafter at every 5 min interval. RESULTS: Fewer patients (3/24 [12.5%]) in Group B had a rise of >50% in systolic blood pressure, from baseline values, after nasal mucosa infiltration as compared with patients in Group A (9/24 [37.5%]). In addition, mean rise in systolic, diastolic and mean arterial pressure was also significantly lower in Group B as compared with Group A. CONCLUSION: Adrenaline in a concentration of 1:400,000 added to 2% lignocaine for nasal mucosa infiltration produces less hemodynamic response as compared with adrenaline 1:200,000 added to 2% lignocaine while at the same time providing similar operating conditions.

Severe autonomic dysreflexia induced cardiac arrest under isoflurane anesthesia in a patient with lower thoracic spine injury.

We present a case of severe autonomic dysreflexia (AD) progressing to cardiac arrest and death under isoflurane anesthesia. Though AD in chronic cervical spine injury is a common entity, occurrence of such an event in the stage of flaccid paralysis in lower dorsal spinal cord injury is rare, especially under general anesthesia. Manipulation of urinary bladder catheter under light plane of isoflurane anesthesia might be the precipitating factor. Increasing concentration of isoflurane failed to abort the episode or might have aggravated it. High level of suspicion and vigilance is necessary to prevent, diagnose and treat such a condition.

Use of continuous renal replacement therapy in acute aluminum phosphide poisoning: a novel therapy.

Aluminum phosphide is most common cause of poisoning in northern India. There is no specific antidote available and management of such cases is mainly supportive with high mortality. We present two cases of severe acute aluminium phosphide poisoning where continuous renal replacement therapy (CRRT) was started early along with other resuscitative measures and both the patients survived.

Anesthetic management of a patient with hypertrophic obstructive cardiomyopathy with dual-chamber pacemaker undergoing transurethral resection of the prostate.

We describe the anesthetic management of a patient with hypertrophic obstructive cardiomyopathy with dual-chamber pacemaker undergoing transurethral resection of the prostate. Anesthetic challenges included prevention and management of perioperative arrhythmias, maintenance of adequate preload, afterload and heart rate to relieve left ventricular outflow tract obstruction and considerations related to the presence of dual-chamber pacemaker and TURP. We recommend preoperative reprogramming of the DDD pacemaker, avoidance of magnet application during the procedure, application of electrosurgical unit current returning pad to the anterior aspect of the thigh, especially if monopolar cautery is used, use of central venous pressure line for estimation of preload and careful titration of anesthetic drugs to maintain stable hemodynamics.