Targeted Temperature Management in Unconscious Survivors of Postcardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: Targeted temperature management (TTM) is a vital element of postresuscitation management after cardiac arrest. Though international guidelines recommend TTM, the supporting evidence is of low certainty. Aims and objectives: To estimate the effect of TTM strategy on mortality and neurological outcomes in postcardiac arrest survivors. Materials and methods: Randomized controlled trials (RCTs) published in English evaluating the use of TTM in adult comatose survivors of cardiac arrest were included. Studies were categorized into two groups, based on hypothermia vs normothermia. The main outcome was death due to any origin. The secondary outcome measures evaluated neurological outcome and complications associated with TTM. Outcomes were analyzed by calculating Odds Ratio (OR) of a worse outcome. ORs with 95% CIs in a forest plot were used to show the results of random-effects meta-analyses. Results: On pooled analysis of 11 RCTs, no difference was observed in death due to any origin rates in the hypothermia compared to the normothermia group (OR; 0.88, 95% CI: 0.39-1.16). Overall, no difference in poor neurological outcome was observed between the two groups (OR; 0.86, 95% CI: 0.66-1.12). Trial sequencing analysis for mortality and poor neurological outcome showed that number to achieve power to predict futility has been achieved in both the parameters. Conclusions: This meta-analysis showed that hypothermia compared to normothermia TTM strategies does not improve survival or neurologic outcomes. How to cite this article: Mishra SB, Patnaik R, Rath A, Samal S, Dash A, Nayak B. Targeted Temperature Management in Unconscious Survivors of Postcardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2022;26(4):506-513.

Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis.

OBJECTIVES: The objective of this review was to compare the effectiveness of Colistin monotherapy and combination therapy for the treatment of multidrug-resistant gram-negative bacterial infections. DATA SOURCES: PubMed, Cochrane Library. STUDY ELIGIBILITY INTERVENTIONS AND EXCLUSIONS: In this systematic review, we included all retrospective and prospective studies and randomized controlled trials (RCTs) that compared intravenous polymyxin monotherapy and combination therapy with any other antibiotic for treating multidrug-resistant infections. Studies using inhaled polymyxins with 5 or less than 5 patients were excluded. The primary outcome was 30-day all-cause mortality and if not reported at day 30 we extracted and documented the closest time point. Both crude outcome rates and adjusted effect estimates were extracted for mortality. STUDY APPRAISAL DATA EXTRACTION AND SYNTHESIS: Search string used was "(Colistin OR polymyxin) AND (Enterobacteriaceae OR Klebsiella OR Acinetobacter OR Escherichia coli OR Pseudomonas) AND (random OR prospective OR retrospective OR cohort OR observational OR blind)." Thirty-nine studies were included in our analysis; out of which 6 RCTs were included and 9 studies used carbapenem as the adjunctive antibiotic. Each study was screened and reviewed for eligibility independently by two authors and data extrapolated on an Excel sheet. RESULTS: The meta-analysis of polymyxin monotherapy vs. combination therapy in multidrug-resistant infections yielded an odds ratio (OR) of 0.81 (95% confidence interval [CI]: 0.65-1.01) with minimal heterogeneity (I 2 = 40%), whereas pooled analysis of this comparison in studies that included carbapenem as combination therapy yielded an OR of 0.64 (CI: 0.40-1.03; I 2 = 62%). Likewise, the pooled analysis of the RCTs yielded an OR of 0.82 (95% CI: 0.58-1.16, I 2 = 22%). All these showed no statistical significance. However, it was seen that polymyxin combination therapy was more effective in multidrug-resistant infections compared to polymyxin monotherapy. The effectiveness was more glaring when carbapenems were used as the combination drug instead of any other antibiotic and more so in many in vitro studies that used polymyxin combination therapy. CONCLUSION: Although statistically insignificant, it would be prudent to use polymyxin combination therapy to treat multidrug-resistant gram-negative bacilli (GNB) infection over monotherapy with preference to use carbapenem as the adjunct alongside polymyxins. HOW TO CITE THIS ARTICLE: Samal S, Mishra SB, Patra SK, Rath A, Dash A, Nayak B, et al. Polymyxin Monotherapy vs. Combination Therapy for the Treatment of Multidrug-resistant Infections: A Systematic Review and Meta-analysis. Indian J Crit Care Med 2021;25(2):199-206.

Comparison between oral melatonin and 24% sucrose for pain management during retinopathy of prematurity screening: a randomized controlled trial.

BACKGROUND: Preterm neonates perceive multiple painful procedures during Neonatal Intensive Care Unit (NICU) stay, having long term neurobehavioral effects. This study aims to compare the analgesic efficacy of oral melatonin with 24% sucrose in neonates during retinopathy of prematurity (ROP) screening. METHODS: A prospective, non-blinded, randomized controlled trial was conducted in a tertiary care NICU. All preterm neonates with gestational age (GA) < 34 weeks or birth weight (BW) < 2000 grams eligible for ROP screening were randomized into oral melatonin (4 mg/kg) and oral 24% sucrose (0.5 ml) groups. Both groups received standard non-pharmacological measures and topical proparacaine. The intensity of pain was measured by Premature Infant Pain Profile (PIPP) score during the procedure, at 1st and 5th minutes following the procedure and compared between the two groups by Mann-Whitney U test with p value < 0.05 considered as significant. RESULTS: A total of 60 preterm neonates were randomized with 30 neonates in the melatonin (median [interquartile range] GA: 30.86 [3.78] weeks, BW: 1160 [430] grams) and 30 neonates in the 24% sucrose (median [IQR] GA: 29.29 [4.68] weeks, BW: 1070 [315] grams) group. The median PIPP score during the procedure in the melatonin and sucrose groups were 17 and 16, respectively (p=0.64). The median (Q1-Q3) PIPP score at the 1st minute was significantly lower among the melatonin group (7 [5.25-10]) vs 24% sucrose group (9.5 [7.25-11]) (p=0.02); and at the 5th minute, the median (Q1-Q3) PIPP scores in the melatonin group (5 [4-6]) was comparable to the 24% sucrose group (5.5 [3.25-7]) (p= 0.52). CONCLUSIONS: Oral melatonin is not inferior to oral 24% sucrose for pain management during ROP screening.

Risk factors and clinical outcomes of carbapenem-resistant Klebsiella pneumonia infection in intensive care unit: A retrospective observational study in a tertiary care hospital in Eastern India.

Background: Carbapenem-resistant Enterobacteriaceae, especially Klebsiella pneumonia, have become a severe global problem with a significant threat to public health, but few studies have investigated the risk factors and epidemiology of carbapenem-resistant K. pneumonia (CRKP) infections in India. Methods: We performed a retrospective observational study of 224 participants with K. pneumoniae who were admitted to the medical intensive care unit (ICU) of Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, between January 1 and December 30, 2020. Antibiotic susceptibility testing was done by automated broth microdilution VITEK® 2 (BioMerieux, Inc., Hazelwood, USA). The Clinical and Laboratory Standards Institute document M100-S22 (January 2020) was used to interpret antimicrobial susceptibility testing. Data were obtained from paper medical records. Results: Two hundred and twenty-four subjects with culture-positive for K. pneumonia were retrieved during the study period, out of which 108 had CRKP. The risk factors for univariate analysis were Acute Physiology and Chronic Health Evaluation II, ICU length of stay (LOS), invasive mechanical ventilator days, central venous catheter days, and arterial line days. The multivariate analysis showed invasive mechanical ventilation and ICU LOS were independent risk factors for CRKP infection. Mortality in the CRKP group was 48 (44%) compared to 27 (23%) in the carbapenem-sensitive K. pneumonia (CSKP) group, which was statistically significant (P < 0.01). Conclusion: Infection due to CRKP in the ICU was associated with 1.9 times higher mortality as compared to CSKP. Invasive mechanical ventilation and ICU LOS were found to be independent risk factors for CRKP infection.

Systematic size mediated trapping of anions of varied dimensionality within a dimeric capsular assembly of a flexible neutral bis-urea platform.

A rationally designed ortho-phenylenediamine based trifluoromethyl meta-disubstituted bis-urea receptor (L) exhibits effective, consistent and systematic binding in its neutral form towards smaller spherical halides (fluoride, chloride, bromide and iodide), and relatively larger planar carbonate and tetrahedral sulphate oxyanions. All the complexes are well characterized both in the solid-state and solution phase. In the presence of excess fluoride anions, the receptor L encapsulates a hydrated cyclic fluoride-water [F2(H2O)2]2- tetramer inside the n-TBA cation sealed dimeric complementary cavity (complex 1). Whereas excess n-TBA/TEA salts of chloride, bromide and iodide result in unusual (Cl-)2, (Br-)2, and (I-)2 doubly encapsulated 2 : 2 dimeric host-guest complexes (2a, 2b, 3 and 4). Two receptor units encapsulate a carbonate ion, via hydroxide induced aerial CO2 fixation (complex 5), and a sulphate anion (complex 6), respectively, in the presence of excess tetrabutylammonium hydroxide and bisulphate salt. 1H NMR titration and 2D NOESY experiments corroborate the solution-state binding and encapsulation of hydrated/non-hydrated halides and oxyanions via N-HA hydrogen bonding.

Fate of over 480 million inhabitants living in arsenic and fluoride endemic Indian districts: Magnitude, health, socio-economic effects and mitigation approaches.

During our last 27 years of field survey in India, we have studied the magnitude of groundwater arsenic and fluoride contamination and its resulting health effects from numerous states. India is the worst groundwater fluoride and arsenic affected country in the world. Fluoride results the most prevalent groundwater related diseases in India. Out of a total 29 states in India, groundwater of 20 states is fluoride affected. Total population of fluoride endemic 201 districts of India is 411 million (40% of Indian population) and more than 66 million people are estimated to be suffering from fluorosis including 6 million children below 14 years of age. Fluoride may cause a crippling disease. In 6 states of the Ganga-Brahmaputra Plain (GB-Plain), 70.4 million people are potentially at risk from groundwater arsenic toxicity. Three additional states in the non GB-Plain are mildly arsenic affected. For arsenic with substantial cumulative exposure can aggravate the risk of cancers along with various other diseases. Clinical effects of fluoride includes abnormal tooth enamel in children; adults had joint pain and deformity of the limbs, spine etc. The affected population chronically exposed to arsenic and fluoride from groundwater is in danger and there is no available medicine for those suffering from the toxicity. Arsenic and fluoride safe water and nutritious food are suggested to prevent further aggravation of toxicity. The World Health Organization (WHO) points out that social problems arising from arsenic and fluoride toxicity eventually create pressure on the economy of the affected areas. In arsenic and fluoride affected areas in India, crisis is not always having too little safe water to satisfy our need, it is the crisis of managing the water.