Prognostic evaluation of quick sequential organ failure assessment score in ICU patients with sepsis across different income settings.

BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions. METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study. RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p < 0.001) and UMIC (p < 0.001) and not HIC (p = 0.220) countries/regions. Similarly, higher 90-day mortality was associated with increased qSOFA in LLMIC (p < 0.001) and UMIC (p < 0.001) only. In contrast, higher 3-day mortality with increasing qSOFA score was observed across all income countries/regions (p < 0.001). Multivariate analysis showed that qSOFA remained associated with 28-day mortality (adjusted RR 1.09 (1.00-1.18), p = 0.038) even after adjustments for covariates including APACHE II, SOFA, income country/region and administration of antibiotics within 3 h. CONCLUSIONS: qSOFA was independently associated with 28-day mortality in ICU patients admitted for sepsis. In LLMIC and UMIC countries/regions, qSOFA was associated with early to late mortality but only early mortality in HIC countries/regions.

Deciphering the Patterns of Dual Primary Cases Registered at the Hospital-Based Cancer Registry: First Experience from Rural Cancer Center in North India.

Objectives The objective is to present the patterns of dual primary malignancies diagnosed at the Pathology Laboratory of Cancer Hospital with the support from hospital-based cancer registry (HBCR), Sangrur, Punjab, India for the years 2018 and 2019. Methods HBCR abstracts data from electronic medical records. Trained cancer registry staff abstracts cases in standard pro forma. Dual primary was coded as per the International Agency for Research on Cancer rule and was rechecked by the pathologist. Statistical Analysis Data about multiple primary was entered and documented in an Excel sheet. Time interval was calculated by subtracting the date of diagnosis for second primary and first primary. Results A total of 6,933 cases were registered, 45 cases are dual primary (26 females, 19 males) of which 64.4% are synchronous and 35.6% metachronous cases. Seventy-nine percent received cancer-directed treatment for synchronous and 87% for metachronous. The most common sites of the primary tumor were breast (33%), head and neck (22.2%), gynecological sites (11%), prostate (9%), esophagus (4%), and remaining other tumors (20.8%). Most common sites for second malignancies were gastrointestinal (GI) tract (31%), gynecological sites (18%), head and neck (16%), hematological malignancies (7%), soft tissue sarcoma (4%), breast (2%), and other sites (22%). Conclusion More than 70% of cases of primary tumors were in breast, head and neck, gynecological, and prostate. Of these, more than 60% of the second malignancy was found in the GI tract, gynecological, and head and neck sites. Around two-thirds of dual tumors are synchronous. Breast cancer cases have higher incidence of second malignancy. Regular follow-up is necessary to assess the survival of the second primary.

Evaluating Determinants of End-of-life Care Provision in Indian Intensive Care Units.

How to cite this article: Myatra SN, Divatia JV, Salins N. Evaluating Determinants of End-of-life Care Provision in Indian Intensive Care Units. Indian J Crit Care Med 2023;27(5):299-300.

Epidemiology, Management, and Outcomes of Sepsis in ICUs among Countries of Differing National Wealth across Asia.

Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. Adult ICU participants admitted for sepsis on four separate days (representing the seasons of 2019) were recruited. Measurements and Main Results: The overall prevalence of sepsis in ICUs was 22.4% (20.9%, 24.5%, and 21.3% in low-income countries/regions [LICs]/lower middle-income countries/regions [LMICs], upper middle-income countries/regions, and high-income countries/regions [HICs], respectively; P < 0.001). Patients were younger and had lower severity of illness in LICs/LMICs. Hospital mortality was 32.6% and marginally significantly higher in LICs/LMICs than HICs on multivariable generalized mixed model analysis (adjusted odds ratio, 1.84; 95% confidence interval, 1.00-3.37; P = 0.049). Sepsis bundle compliance was 21.5% at 1 hour (26.0%, 22.1%, and 16.2% in LICs/LMICs, upper middle-income countries/regions, and HICs, respectively; P < 0.001) and 36.6% at 3 hours (39.3%, 32.8%, and 38.5%, respectively; P = 0.001). Delaying antibiotic administration beyond 3 hours was the only element independently associated with increased mortality (adjusted odds ratio, 2.53; 95% confidence interval, 2.07-3.08; P < 0.001). Conclusions: Sepsis is a common cause of admission to Asian ICUs. Mortality remains high and is higher in LICs/LMICs after controlling for confounders. Sepsis bundle compliance remains low. Delaying antibiotic administration beyond 3 hours from diagnosis is associated with increased mortality. Clinical trial registered with www.ctri.nic.in (CTRI/2019/01/016898).

Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia.

PURPOSE: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. METHODS: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. RESULTS: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). CONCLUSION: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

The physiologically difficult airway: an emerging concept.

PURPOSE OF REVIEW: The physiologically difficult airway is one in which physiologic alterations in the patient increase the risk for cardiorespiratory and other complications during tracheal intubation and transition to positive pressure ventilation. This review will summarize the recent literature around the emerging concept of the physiologically difficult airway, describe its relevance and various patient types in which this entity is observed. RECENT FINDINGS: Physiologic derangements during airway management occur due acute illness, pre-existing disease, effects of anesthetic agents, and positive pressure ventilation. These derangements are especially recognized in critically ill patients, but can also occur in otherwise healthy patients including obese, pregnant and pediatric patients who have certain physiological alterations. Critically ill patients may have a physiologically difficult airway due to the presence of acute respiratory failure, hypoxemia, hypotension, severe metabolic acidosis, right ventricular failure, intracranial hypertension, and risk of aspiration of gastric contents during tracheal intubation. SUMMARY: Understanding the physiological alterations and the risks involved in patients with a physiologically difficult airway is necessary to optimize the physiology and adopt strategies to avoid complications during tracheal intubation. Further research will help us better understand the optimal strategies to improve outcomes in these patients.

The impact of COVID-19 on health care-associated infections in intensive care units in low- and middle-income countries: International Nosocomial Infection Control Consortium (INICC) findings.

BACKGROUND: This study examines the impact of the COVID-19 pandemic on health care-associated infection (HAI) incidence in low- and middle-income countries (LMICs). METHODS: Patients from 7 LMICs were followed up during hospital intensive care unit (ICU) stays from January 2019 to May 2020. HAI rates were calculated using the International Nosocomial Infection Control Consortium (INICC) Surveillance Online System applying the Centers for Disease Control and Prevention's National Healthcare Safety Network (CDC-NHSN) criteria. Pre-COVID-19 rates for 2019 were compared with COVID-19 era rates for 2020 for central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), mortality, and length of stay (LOS). RESULTS: A total of 7,775 patients were followed up for 49,506 bed days. The 2019 to 2020 rate comparisons were 2.54 and 4.73 CLABSIs per 1,000 central line days (risk ratio [RR] = 1.85, p = .0006), 9.71 and 12.58 VAEs per 1,000 mechanical ventilator days (RR = 1.29, p = .10), and 1.64 and 1.43 CAUTIs per 1,000 urinary catheter days (RR = 1.14; p = .69). Mortality rates were 15.2% and 23.2% for 2019 and 2020 (RR = 1.42; p < .0001), respectively. Mean LOS for 2019 and 2020 were 6.02 and 7.54 days (RR = 1.21, p < .0001), respectively. DISCUSSION: This study documents an increase in HAI rates in 7 LMICs during the first 5 months of the COVID-19 pandemic and highlights the need to reprioritize and return to conventional infection prevention practices.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

The story of critical care in Asia: a narrative review.

BACKGROUND: Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia. MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty. CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.

Identification of patients for a delayed extubation strategy versus elective tracheostomy for postoperative airway management in major oral cancer surgery: A prospective observational study in seven hundred and twenty patients.

OBJECTIVES: Tracheostomy (TT) and delayed extubation (DE) are two approaches to postoperative airway management in patients after major oral cancer surgery. We planned a study to determine the safety of overnight intubation followed by extubation the next morning (DE) compared to elective TT and to identify factors that were associated with a safe DE (maintenance of a patent airway). MATERIAL AND METHODS: We conducted a prospective observational study in a tertiary referral cancer care center. We included adult patients undergoing elective major oral cancer surgery under general anesthesia with tracheal intubation. The decision regarding postoperative airway management using either TT or DE was made according to the usual practice at our center. RESULTS: We screened a total of 4477 patients, 720 patients were included. DE was performed in 417 patients (58.4%) and TT in 303 patients (42.4%). On multivariable analysis, T1-T2 tumor stage, absence of extensive resection, primary closure or reconstruction using fasciocutaneous flap, absence of preoperative radiation, no neck dissection or unilateral neck dissection and shorter duration of anesthesia were independent predictors for a safe DE. Overall complications (4.3% versus 22.5%, p = 0.00) and airway complications (1.7% versus 8.7%, p = 0.00) were lower in the DE compared to the TT group respectively. DE was associated with a shorter hospital stay (7.2 ± 3.7 versus 11.5 ± 7.2 days, p = 0.00), time to oral intake and speech compared to TT. CONCLUSIONS: A DE strategy after major oral cancer surgery is a safe alternative to TT in a select group of patients.

Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. METHODS: This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. DISCUSSION: This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

All India difficult airway association (AIDAA) consensus guidelines for airway management in the operating room during the COVID-19 pandemic.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) which causes coronavirus disease (COVID-19) is a highly contagious virus. The closed environment of the operation room (OR) with aerosol generating airway management procedures increases the risk of transmission of infection among the anaesthesiologists and other OR personnel. Wearing complete, fluid impermeable personal protective equipment (PPE) for airway related procedures is recommended. Team preparation, clear methods of communication and appropriate donning and doffing of PPEs are essential to prevent spread of the infection. Optimal pre oxygenation, rapid sequence induction and video laryngoscope aided tracheal intubation (TI) are recommended. Supraglottic airways (SGA) and surgical cricothyroidotomy should be preferred for airway rescue. High flow nasal oxygen, face mask ventilation, nebulisation, small bore cannula cricothyroidotomy with jet ventilation should be avoided. Tracheal extubation should be conducted with the same levels of precaution as TI. The All India Difficult Airway Association (AIDAA) aims to provide consensus guidelines for safe airway management in the OR, while attempting to prevent transmission of infection to the OR personnel during the COVID-19 pandemic.

Critical language during an airway emergency: Time to rethink terminology?

Clear language should be used during emergency airway management to aid communication and understand the nature of the emergency. Unfortunately, during emergency airway management, there is no uniform language used for communication. Various difficult airway guidelines use different terminologies. Terminologies like "can't intubate, can't oxygenate" (CICO) and "can't intubate, can't ventilate" (CICV) have certain limitations. Though terminology like "Front of Neck Access" (FONA) is dominant in the literature,"emergency cricothyroidotomy" is used more often in clinical practice, suggesting a disconnect between the dominant terminology in the literature and in clinical practice. Terminology should not be used merely because it is catchy, simple and advocated by a few. It must accurately reflect the nature of the situation, convey a sense of urgency, and suggest an action sequence. An initiative to achieve consensus among existing terminologies is much needed. Leaders in the field should work towards refining airway terminology and replace poor phrases with ones that are more concise, precise and can be used universally in an airway emergency.

Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations.

As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria.

BACKGROUND: Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100. METHODS: Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used. RESULTS: A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H). CONCLUSIONS: In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.

Compression-only life support (COLS) for cardiopulmonary resuscitation by layperson outside the hospital.

The cardiopulmonary resuscitation (CPR) guidelines of compression-only life support (COLS) for management of the victim with cardiopulmonary arrest in adults provide a stepwise algorithmic approach for optimal outcome of the victim outside the hospital by untrained laypersons. These guidelines have been developed to recommend practical, uniform and acceptable resuscitation algorithms across India. As resuscitation data of the Indian population are inadequate, these guidelines have been based on international literature. The guidelines have been recommended after discussion among Indian experts and the recommendations modified to ensure its practical applicability across the country. The COLS emphasises on early recognition of cardiac arrest and activation, early chest compression and early transfer to medical facility. The guidelines emphasise avoidance of any interruption of chest compression, and thus relies primarily on chest compression-only CPR by laypersons.