Approach to Intensive Care Costing and Provision of Cost-effective Care.

Intensive care unit (ICU) service is resource-intense, finite, and valuable. The outcome of critically ill patients has improved because of a better understanding of disease pathology, technological developments, and newer treatment modalities. These improvements have however come at a price, with ICUs contributing significantly to health budgets. Several costing tools are used to assess cost. Accurate assessment has been hampered by the lack of standardized methodology and the heterogeneity of ICUs. In a costing exercise, the level of disaggregation (micro-costing vs gross-costing) and the method of costing (top-down vs bottom-up) need to be considered. Intensive care unit costing also needs to be viewed from the perspective of stakeholders. While all stakeholders aim to provide quality health care, objectives may vary. For the public health care provider, the focus is on optimizing expenditure; for the private health care provider it is bottomline; for a patient, it is affordability; for an insurance service provider, it is minimizing payout; and for the regulator, it is ensuring quality standards and fair pricing. The field of health economics deals with the application of the principles of cost-minimization, cost-effectiveness, cost-utility, and cost-benefit to identify treatments that result in the best outcome at the lowest cost, without limiting resources to other competing interests. In the ICU setting, studies on the efficient use of available resources, and interventions that reduce cost and minimize avoidable cost, would not only translate to cost savings, lives saved, and quality-adjusted life years gained but also enable policymakers to better allocate health care resources. How to cite this article: Chacko B, Ramakrishnan N, Peter JV. Approach to Intensive Care Costing and Provision of Cost-effective Care. Indian J Crit Care Med 2023;27(12):876-887.

Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study.

Introduction: The effectiveness of gastric lavage in organophosphorus (OP) poisoning has not been established. We assessed the ability of gastric lavage to remove OP insecticides as a preliminary stage in assessing effectiveness. Patients and methods: Organophosphorus poisoning patients presenting within 6 hours were included, irrespective of prior gastric lavage. A nasogastric tube was placed and gastric contents aspirated, followed by at least three cycles of gastric lavage with 200 mL of water. Samples from the initial aspirate and the first three lavage cycles were sent for identification and quantification of the OP compounds. Patients were monitored for complications of gastric lavage. Results: Around 42 patients underwent gastric lavage. Eight (19.0%) patients were excluded from the study because of a lack of analytical standards for ingested compounds. Insecticides were detectable in the lavage samples of 24 of 34 (70.6%) patients. Lipophilic OP compounds were detected in 23 of 24 patients, while no hydrophilic OP compounds could be detected in six patients with reported ingestion of hydrophilic compounds. For chlorpyrifos poisoning (n = 10), only 0.65 mg (SD 1.2) of the estimated ingested amount (n = 5) of 8,600 mg (SD 3,200) was recovered by gastric lavage. The mean proportion of the compound removed by initial gastric aspirate was 79.4% and subsequent three cycles removed 11.5, 6.6, and 2.7%. Conclusion: Lipophilic OP insecticides could be quantified in the stomach contents of OP poisoning patients with the first aspiration or lavage being most effective. The amount removed was very low; hence, routine use of gastric lavage for OP poisoning patients arriving within 6 hours is unlikely to be beneficial. How to cite this article: Mathansingh AJ, Jose A, Fleming JJ, Abhilash KPP, Chandiraseharan VK, Lenin A, et al. Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study. Indian J Crit Care Med 2023;27(6):397-402.

Effectiveness of a monitored home isolation program for COVID-19 infection during the second wave of the pandemic.

Background: The rapidity of spread of COVID-19 infection during the second wave of the pandemic placed tremendous stress on healthcare resources. This study evaluated the effectiveness of a monitored home isolation (HI) program. Methods: In this descriptive longitudinal study, symptomatic patients were screened in the HI clinic and eligible patients were followed up at home using tele-consultation, until recovery or hospitalization. HI failure was defined as need for hospitalization. Factors associated with HI failure were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Results: During April and May 2021, 1957 RT-PCR confirmed patients (984 male) with mean (SD) age 40 (13.5) years were enrolled; 93.3% (n = 1825) were successfully managed at home. Of the 132 patients (6.7%) who failed HI, 57 (43.2%) required oxygen therapy and 23 needed intensive care admissions. Overall mortality was 0.4% (7/1957). On adjusted analysis, factors associated with HI failure were age ≥60 years (OR 2.24; 95%CI 1.26-3.99), male gender (OR 2.26; 95%CI 1.44-3.57), subjective reporting of breathing difficulty (OR 3.64; 95%CI 2.08-6.37), history of cough (OR 2.08; 95%CI 1.37-3.17), and higher heart rate (OR 1.04; 95%CI 1.02-1.05). Although patient status (non-healthcare workers), no prior vaccination and ≥2 comorbidities were associated with HI failure on unadjusted analysis, these were non-significant on adjusted analysis. Conclusion: Monitored HI program can be used successfully during a pandemic wave to judicially use scare hospital resources. Older male patients presenting with breathlessness or cough may warrant closer monitoring.

Levonadifloxacin, a recently approved benzoquinolizine fluoroquinolone, exhibits potent in vitro activity against contemporary Staphylococcus aureus isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital.

OBJECTIVES: Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoquinolizine fluoroquinolones, recently approved in India for the treatment of acute bacterial skin and skin structure infections with concurrent bacteraemia and diabetic foot infections. Ahead of its market launch, the present study aimed to assess the in vitro activity of levonadifloxacin against contemporary Staphylococcus aureus isolates collected from a large tertiary care hospital in India. Additionally, levonadifloxacin activity was tested against hVISA and Bengal Bay clone MRSA isolates. METHODS: Non-duplicate S. aureus (n = 793) isolates collected at Christian Medical College hospital, Vellore, India during 2013-19 were included in the study. MRSA isolates were identified using a cefoxitin disc diffusion assay. MICs of levonadifloxacin and comparator antibiotics were determined using the broth microdilution method. Mutations in QRDRs were identified for selected levofloxacin-non-susceptible isolates. MLST profiling was undertaken to detect the Bengal Bay clone. RESULTS: Among the 793 isolates, 441 (55.6%) were MRSA and 626 (78.9%) were non-susceptible to levofloxacin. Levonadifloxacin showed MIC50 and MIC90 values of 0.25 and 0.5 mg/L, respectively, for all S. aureus, which included hVISA and Bengal Bay clone MRSA. The potency of levonadifloxacin was 16 times superior compared with levofloxacin. CONCLUSIONS: The present study demonstrated potent activity of levonadifloxacin against contemporary S. aureus isolates, which included MRSA isolates, hVISA isolates, Bengal Bay clone isolates and a high proportion of quinolone-non-susceptible isolates. The potent activity of levonadifloxacin observed in this study supports its clinical use for the treatment of S. aureus infections.

An observational study on the practice of noninvasive ventilation at a tertiary level Australian intensive care unit.

BACKGROUND: Failure of Non-Invasive Ventilation (NIV) is associated with increased morbidity and mortality among critically ill patients. Although there is evidence of association between disease related factors and NIV failure, it is unclear whether factors related to NIV application contribute to NIV failure. OBJECTIVES: To evaluate NIV failure rate and factors associated with NIV failure. DESIGN, SETTINGS AND OUTCOMES: Prospective, observational, pilot study conducted in a 23-bed, tertiary care Intensive Care Unit (ICU). NIV failure was defined as application of NIV resulting in intubation or death in ICU. RESULTS: Amongst 238 patients admitted with respiratory failure, NIV was administered to 60 patients (34 males, 26 females) for a total of 70 application episodes. The etiology of respiratory failure included acute pulmonary edema (28.6%), acute lung injury (22.9%) and pneumonia (15.7%). The mean (SD) age was 62 (17.6) years, BMI 32.0 (8.5) kg/m2 and median APACHE-II score 17.5 (14.0-23.8). NIV failure occurred in 22 out of 70 applications (31.4% [95%CI 20.0-43.0]). NIV failure assessed by simple logistic regression analysis, was associated with admission diagnosis (OR 6.0, 95%CI: 1.3-28.7, p = 0.03), use of bi-level NIV-PS (OR 5.00, 95%CI: 1.04-24.1, p = 0.04), presence of nasogastric tube (OR 6.20, 95%CI: 1.9-19.8, p < 0.01) and with short NIV breaks in the 2nd 24-hours (OR 0.96, 95%CI: 0.91-0.99, p = 0.04). CONCLUSION: NIV failure was observed in 31.4%. Factors associated with NIV failure were etiology of respiratory illness, type of NIV support and short NIV breaks, presumably reflecting illness severity or progress of disease. The presence of a nasogastric tube during application of NIV may adversely impact NIV application.

Reversal of Anticoagulants in Critical Care.

There has seen an increase in anticoagulant consumption worldwide over the past few decades. With this widespread utilization of anticoagulants, clinicians are increasingly likely to encounter situations where anticoagulants would need to be withheld. This includes emergency and elective procedures or surgeries as well as major or minor bleeding as a direct result of over anticoagulation or consequent to other intercurrent illnesses such as sepsis or trauma with multiorgan failure, where the anticoagulant may contribute to coagulation abnormalities. Clinicians are required to have a thorough understanding of the indications for anticoagulant prescription, drug interactions and monitoring, indications and options of reversal of anticoagulation and management of bleeding in the situations described above. Once the acute process is managed, the ongoing need and timing of reinitiation of anticoagulation is also crucial. This article provides an overview on the indications for reversal of anticoagulation, the agents used for reversal and the timing of reinitiation of anticoagulants. HOW TO CITE THIS ARTICLE: Chacko B, Peter JV, Subramani K. Reversal of Anticoagulants in Critical Care. Indian J Crit Care Med 2019;23(Suppl 3):S221-S225.

Cytomorphometric Neutrophil and Monocyte Markers May Strengthen the Diagnosis of Sepsis.

BACKGROUND:: The diagnosis of sepsis is challenging in the absence of a gold standard test. Recent studies have explored the role of neutrophil and monocyte volume, conductivity, and scatter (VCS), derived from automated hematology analyzers, in diagnosing sepsis. We assessed the diagnostic accuracy of VCS parameters in critically ill patients with sepsis. METHODOLOGY:: In this prospective study, VCS parameters, procalcitonin, and C-reactive protein (CRP) were assessed in patients with proven sepsis (cases) and 2 control groups (intensive care unit [ICU] patients without sepsis and healthy blood donors). The diagnostic property of each test was explored by calculating sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC). RESULTS:: The study included 65 patients with sepsis, 58 nonseptic ICU controls, and 98 blood donors. Procalcitonin and CRP were not significantly different ( P > .06) between patients with sepsis and nonseptic patients. Mean (95% confidence interval [CI]) neutrophil volume (MNV) was significantly higher ( P < .001) in patients with sepsis (165.5; 95%CI 161.6-169.4) than in nonseptic (157.3; 95%CI 154.6-160.1) patients and donors (148.9; 95%CI 147.9-150). A similar pattern was seen with mean monocyte volume (MMoV). Neutrophil and monocyte conductivity and scatter parameters were variably associated. The AUC was highest for MMoV (0.74) and lowest for CRP (0.62). Among all parameters, MNV and MMoV had the highest specificity of 85% and 80%, respectively. CONCLUSION:: In critically ill patients with suspected sepsis, VCS parameters may help strengthen the diagnostic probability of sepsis. Future studies may explore the role of serial monitoring of VCS to track response to antimicrobial therapy.

Antinuclear antibodies in scrub typhus: Transient occurrence during acute illness.

BACKGROUND & OBJECTIVES: The pathological hallmark of scrub typhus infection is focal or disseminated vasculitis. As with other infections, antinuclear antibodies (ANA) have been previously described in scrub typhus. However, the underlying mechanisms and implications of this immunological phenomenon is not well understood. In the present work it was assessed whether ANA is associated with illness severity and outcomes. METHODS: In this prospective study spanning one year, patients fulfilling the diagnostic criteria for scrub typhus were recruited. Patients with other acute infective febrile illnesses were taken as controls. ANA positivity was compared between the cases and controls. ANA in scrub typhus was assessed for correlation with disease severity, organ dysfunction and outcomes. RESULTS: The cohort comprised of 149 patients (scrub 89; controls 60) with mean age 46.5 (SD=16.9) yr; 48.3% were female. ANA was detected in 48 (53.9%) patients with scrub typhus and 9(15%) controls (p < 0.001). The ANA pattern was predominantly speckled (93.8%) in both scrub typhus patients and controls. In patients with scrub typhus, ANA positivity was associated with increasing APACHE-III score [Odds ratio (OR) 1.01; 95% CI 0.99-1.03; p = 0.09]. On bivariate analysis, ANA tended to be correlated with acute respiratory distress syndrome (OR 2.32; 95% CI 0.98-5.46; p = 0.06), hepatic dysfunction (OR 2.25; 95% CI 0.94-5.39, p = 0.06) and aseptic meningitis (OR 6.83; 95% CI 0.80-58.05, p = 0.08). The presence of these antibodies did not correlate with duration of hospitalization or mortality. Convalescent sera on 31 ANA positive scrub typhus patients demonstrated persistence of ANA in only 5 (16.1%) patients. INTERPRETATION & CONCLUSION: The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of scrub typhus infection. Its association with organ dysfunction warrants further study of the mechanisms and impact of autoantibody formation in scrub typhus.

Caregiver perceptions on intensive care: A qualitative study from southern India.

BACKGROUND: Admission of a patient to an intensive care unit (ICU) can result in tremendous stress to family caregivers not only because of the need to provide physical and emotional support to the sick relative, but also due to the burden of decision-making on behalf of the critically ill person. We enquired about family caregivers' perspectives on intensive care, the challenges they faced with decision-making and their perceptions on the nature of their interactions with healthcare providers. METHODS: We used maximum variation sampling and enrolled 20 consenting caregivers for semi-structured interviews. Each interview, based on an interview guide, took 30-40 minutes and was conducted in a private place within the hospital premises. All interviews were recorded, transcribed verbatim and entered into a qualitative software (NVivo) for analysis. RESULTS: The three emergent themes of analysis were (i) understanding about ICU, (ii) decision-making concerning ongoing treatment; and (iii) relationship with healthcare-providers. Some respondents saw the intensive care as an expensive facility for seriously ill patients while others were not so clear. The family's relationship with the patient and their financial status were seen as important deciding factors in continuing treatment. Decision-making was a complex and emotional issue and doctors were held in awe and seen as the main deciding authority. The importance of doctors being compassionate and communicative was stressed. CONCLUSION: Our study highlights the problems faced by family caregivers and of the need to improve their satisfaction through clear and simple communication strategies.

COST OF INTENSIVE CARE IN INDIA.

OBJECTIVES: The majority of patients in India access private sector providers for curative medical services. However, there is scanty information on the cost of treatment of critically ill patients in this setting. The study evaluates the cost and extent of financial subsidy required for patients admitted to an intensive care unit (ICU) in India. METHODS: Data on direct medical, direct nonmedical, and indirect cost were prospectively collected from critically ill patients admitted to a tertiary teaching hospital in India. Willingness-to-pay (WTP) amount was obtained from the next-of-kin following admission and the actual cost paid by the family at discharge was recorded. RESULTS: The main diagnoses (n = 499) were infection (26 percent) and poisoning (21 percent). The mean APACHE-II score was 13.9 (95 percent confidence interval [CI], 13.3-14.5); 86 percent were ventilated. ICU stay was 7.8 days (95 percent CI, 7.3-8.3). Hospital mortality was 27.9 percent. Direct medical cost accounted for 77 percent (US$ 2164) of the total treatment cost (US$ 2818). Indirect cost and direct nonmedical cost contributed to 19 percent (US$ 547.5) and 4 percent (US$ 106.5), respectively. Average total and daily ICU cost were US$ 1,897 and US$ 255, respectively. Although the family's WTP was 53 percent (US$ 1146; 95 percent CI, 1090-1204) of direct medical cost, their final contribution was 67.7 percent (US$ 1465; 95 percent CI, 1327-1604). CONCLUSIONS: The cost of an ICU admission in our setting is US$ 2818. Although the family's contribution to expenses exceeded their initial WTP, a substantial subsidy (33 percent) is still required. Alternate financing strategies for the poor and optimization of ICU resources are urgently required.

Supraphysiological 25-hydroxy vitamin D3 level at admission is associated with illness severity and mortality in critically ill patients.

We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37% (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5% (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers. Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75% (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5% (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7% (95% confidence interval 1.2-11.4; p = 0.03), respectively. In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality. A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality. Extrinsic factors interfering with test results were ruled out. A biological hypothesis to explain this observation is proposed. Further clarification of mechanisms leading to this observation is warranted.

Clinical profile of childhood-onset psoriasis and prevalence of HLA-Cw6: a hospital-based study from India.

BACKGROUND: Childhood-onset psoriasis (COP), a distinct clinical entity, may be associated with HLA-Cw6 positivity and metabolic and cardiovascular complications. There is some evidence that HLA-Cw6 positivity is associated with more extensive or severe disease and that positivity is lower in Asian patients than in Caucasians. We describe the clinical profile, prevalence of the HLA-Cw6 allele, metabolic syndrome (MetS) and vitamin D deficiency in Indian patients with COP. METHODS: In this cross-sectional hospital-based study over 15 months (June 2010-August 2011), 108 consecutive patients with disease onset ≤16 years were enrolled. Demographic, clinical and laboratory data were collected. Patients were categorised as children with COP (CCOP; n=69) or adults with COP (ACOP; n=39). Disease severity was assessed using body surface area (BSA) involved and Psoriasis Area and Severity Index (PASI) score. RESULTS: The most common morphological type was chronic plaque psoriasis; follicular psoriasis was seen only in children. Adults with disease onset in childhood, when compared with CCOP, had later disease onset (11.0±4.0 vs 6.9±3.8 (mean±SD) years; p<0.0001) of greater severity (p=0.021) based on BSA involved. PASI scores were, however, similar in ACOP and CCOP. Body mass index was not associated with disease severity. Of the 83 who underwent HLA-C typing, 46 (55.4%) were positive; positivity was associated with guttate lesions (p=0.031), scalp involvement (p=0.004), greater BSA involvement (p=0.002) and higher PASI scores (p=0.013). Vitamin D deficiency, obesity and MetS were present in 77.4%, 10.7% and 14.5% of patients, respectively. CONCLUSIONS: Among Indian patients, CCOP have earlier disease onset than ACOP. HLA-Cw6 was associated with guttate psoriasis, scalp involvement and disease severity. Vitamin D deficiency was common.

Association between a prolonged corrected QT interval and outcomes in patients in a medical Intensive Care Unit.

INTRODUCTION: Patients admitted into a medical Intensive Care Unit (ICU) have varying illnesses and risk factors. An electrocardiogram (ECG) is a useful tool to assess the cardiac status. The aim of the study was to determine the prevalence of QT prolongation of the ECG in patients admitted to a medical ICU in a tertiary hospital, to assess outcomes in terms of mortality, cardiovascular events, and duration of ICU stay. MATERIALS AND METHODS: Prospective observational study, 6 months duration, assessing the prevalence of prolonged corrected QT interval (QTc) at admission into a medical ICU. A QTc calculated by Bazett's formula, of >440 ms for males and >460 ms for females was considered prolonged. Details of illness, clinical and lab parameters were monitored. RESULTS: The total number of patients screened was 182. There was a high prevalence of prolonged QTc (30%) on admission to the ICU. This reduced to 19% on day 3 (P = 0.011). In patients with a prolonged QTc the odds ratio of adverse outcome from ICU was 3.17 (confidence interval [CI]: 1.52-6.63) (P = 0.001) and of adverse outcome for hospital stay was 2.27 (CI: 1.11-4.66) (P = 0.014). In the study, 35% of all patients received drugs with QT prolonging action. Of patients with a prolonged QTc at admission 18 (35%) received a QT prolonging drug. CONCLUSIONS: We found that prolonged QTc is common (30%) in our medical ICU at admission and a large proportion (35%) received drugs capable of prolonging QT interval. These patients with QTc prolongation have a higher odds ratio for adverse outcomes.

Patterns of central venous oxygen saturation, lactate and veno-arterial CO2 difference in patients with septic shock.

BACKGROUND AND AIMS: Tissue hypoperfusion is reflected by metabolic parameters such as lactate, central venous oxygen saturation (ScvO2) and the veno-arterial CO2 (vaCO2) difference. We studied the relation of these parameters over time and with outcome in patients with severe septic shock. MATERIALS AND METHODS: In this single-center, prospective observational cohort study, adult patients (≥18 years) with circulatory shock were included. Echocardiography and simultaneous arterial and venous blood gases were done on enrolment (0 h) and at 24, 48 and 72 h. The partial pressure of CO2, lactate and ScvO2 were recorded from the central venous blood samples. The vaCO2 was calculated as the difference in CO2 between paired venous and arterial blood gas samples. RESULTS: Of the 104 patients with circulatory shock, 79 patients (44 males) with septic shock aged 49.8 (standard deviation ± 14.6) years and with sequential organ failure assessment (SOFA) score of 11.0 ± 3.4 were included. 71 patients (89.9%) were ventilated (11.4 ± 12.3 ventilator-free days). The duration of hospitalization was 16.6 ± 12.8 days and hospital mortality 50.6%. Lactate significantly decreased over time with a greater decrement in survivors than nonsurvivors (-0.35 vs. -0.10, P < 0.001). For every l/min increase in cardiac output, vaCO2 decreased by 0.34 mmHg (P = 0.006). There was no association between ScvO2 and mortality (P = 0.930). 0 h SOFA and vaCO2 ≤6 mmHg were strongly associated (P = 0.005, P = 0.018, respectively) with higher odds of mortality. However, this association was evident only in those with ScvO2 >70% and not in ScvO2 ≤70%. CONCLUSION: In septic shock, vaCO2 ≤6 mmHg is independently associated with mortality, particularly in those with normalized ScvO2 consistent with metabolic microcirculatory abnormalities in these patients.

Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis.

OBJECTIVE: The objective of the following study is to evaluate the associations between single nucleotide polymorphisms (SNPs) in the Heat Shock Protein 70 (HSP70) gene, gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and medical intensive care unit (MICU) stay and organ failure in sepsis. MATERIALS AND METHODS: MICU patients with sepsis were genotyped for rs1061581, rs2227956, rs1008438 and rs1043618 polymorphisms in HSP70 gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis or allele-specific PCR. Messenger ribonucleic acid (mRNA) expression of IL-6 and TNF-α were quantitated in peripheral blood lymphocytes. Outcomes were recorded. RESULTS: 108 patients (48 male) aged 40.7 ± 16.0 (mean ± standard deviation) years included H1N1 infection (36), scrub typhus (29) and urosepsis (12). Seventy-one (65.7%) had dysfunction of three or more organ systems, 66 patients (61.1%) were treated by mechanical ventilation, 21 (19.4%) needed dialysis. ICU stay was 9.3 ± 7.3 days. Mortality was 38.9%. One or more SNPs were noted in 101/108 (93.5%) and organ failure was noted in only 1/7 patients without a single SNP. The A allelotypes of rs1061581 and rs1008438 were associated with hematological dysfunction (P = 0.03 and 0.07) and longer ICU stay (P = 0.05 and 0.04), whereas IL-6 and TNF-α mRNA levels were associated with central nervous system dysfunction. CONCLUSIONS: HSP70 genotypes may determine some adverse outcomes in patients with sepsis.

Clinical features of organophosphate poisoning: A review of different classification systems and approaches.

PURPOSE: The typical toxidrome in organophosphate (OP) poisoning comprises of the Salivation, Lacrimation, Urination, Defecation, Gastric cramps, Emesis (SLUDGE) symptoms. However, several other manifestations are described. We review the spectrum of symptoms and signs in OP poisoning as well as the different approaches to clinical features in these patients. MATERIALS AND METHODS: Articles were obtained by electronic search of PubMed(®) between 1966 and April 2014 using the search terms organophosphorus compounds or phosphoric acid esters AND poison or poisoning AND manifestations. RESULTS: Of the 5026 articles on OP poisoning, 2584 articles pertained to human poisoning; 452 articles focusing on clinical manifestations in human OP poisoning were retrieved for detailed evaluation. In addition to the traditional approach of symptoms and signs of OP poisoning as peripheral (muscarinic, nicotinic) and central nervous system receptor stimulation, symptoms were alternatively approached using a time-based classification. In this, symptom onset was categorized as acute (within 24-h), delayed (24-h to 2-week) or late (beyond 2-week). Although most symptoms occur with minutes or hours following acute exposure, delayed onset symptoms occurring after a period of minimal or mild symptoms, may impact treatment and timing of the discharge following acute exposure. Symptoms and signs were also viewed as an organ specific as cardiovascular, respiratory or neurological manifestations. An organ specific approach enables focused management of individual organ dysfunction that may vary with different OP compounds. CONCLUSIONS: Different approaches to the symptoms and signs in OP poisoning may better our understanding of the underlying mechanism that in turn may assist with the management of acutely poisoned patients.

Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission.

BACKGROUND AND AIMS: Scrub typhus, a zoonotic rickettsial infection, is an important reason for intensive care unit (ICU) admission in the Indian subcontinent. We describe the clinical profile, organ dysfunction, and predictors of mortality of severe scrub typhus infection. MATERIALS AND METHODS: Retrospective study of patients admitted with scrub typhus infection to a tertiary care university affiliated teaching hospital in India during a 21-month period. RESULTS: The cohort (n = 116) aged 40.0 ± 15.2 years (mean ± SD), presented 8.5 ± 4.4 days after symptom onset. Common symptoms included fever (100%), breathlessness (68.5%), and altered mental status (25.5%). Forty-seven (41.6%) patients had an eschar. Admission APACHE-II score was 19.6 ± 8.2. Ninety-one (85.2%) patients had dysfunction of 3 or more organ systems. Respiratory (96.6%) and hematological (86.2%) dysfunction were frequent. Mechanical ventilation was required in 102 (87.9%) patients, of whom 14 (12.1%) were solely managed with non-invasive ventilation. Thirteen patients (11.2%) required dialysis. Duration of hospital stay was 10.7 ± 9.7 days. Actual hospital mortality (24.1%) was less than predicted APACHE-II mortality (36%; 95% Confidence interval 32-41). APACHE-II score and duration of fever were independently associated with mortality on logistic regression analysis. CONCLUSIONS: In this cohort of severe scrub typhus infection with multi-organ dysfunction, survival was good despite high severity of illness scores. APACHE-II score and duration of fever independently predicted mortality.

Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis.

OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs). DESIGN AND SETTING: Systematic review and frequentist network meta-analysis using standard methodological procedures as recommended by Cochrane for screening of records, data extraction and analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. PARTICIPANTS: Randomised controlled trials involving patients admitted to ICUs for longer than 24 hours were included. SEARCH METHODS: The Cochrane Gut Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Latin American and Caribbean Health Science Information database (LILACS) databases were searched from August 2017 to March 2022. The search in MEDLINE was updated in April 2023. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). MAIN OUTCOME MEASURES: The primary outcome was the prevention of clinically important upper GI bleeding. RESULTS: We included 123 studies with 46 996 participants. Cimetidine (relative risk (RR) 0.56, 95% CI 0.40 to 0.77, moderate certainty), ranitidine (RR 0.54, 95% CI 0.38 to 0.76, moderate certainty), antacids (RR 0.48, 95% CI 0.33 to 0.68, moderate certainty), sucralfate (RR 0.54, 95% CI 0.39 to 0.75, moderate certainty) and a combination of ranitidine and antacids (RR 0.13, 95% CI 0.03 to 0.62, moderate certainty) are likely effective in preventing upper GI bleeding.The effect of any intervention on the prevention of nosocomial pneumonia, all-cause mortality in the ICU or the hospital, duration of the stay in the ICU, duration of intubation and (serious) adverse events remains unclear. CONCLUSIONS: Several interventions seem effective in preventing clinically important upper GI bleeding while there is limited evidence for other outcomes. Patient-relevant benefits and harms need to be assessed under consideration of the patients' underlying conditions.

Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7-14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26-4.55 ng/ml; Soluble P-selectin = 13.5-31.5 ng/ml; BTG = 0.034-1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.