What is the right temperature to cool post-cardiac arrest patients?

Background: Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34°C for 12 to 24hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome. Methods: Objective: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36°C reduces all-cause mortality compared with a moderate hypothermia of 33°C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures. Design: A multicenter, international, open label, randomized controlled trial. Setting: Thirty-six ICUs in Europe and Australia participated in this study. Participants: Unconscious adults (older than 18years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20minutes without chest compressions). Intervention: The above participant cohorts were randomized to targeted body temperature of either 33°C or 36°C for 36hours after the CA with gradual rewarming of both groups to 37°C (hourly increments of 0.5°C) after the initial 28hours. Body temperatures in both the groups were then maintained below 37.5°C for 72hours after the initial 36hours. Outcomes: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180days were studied. Results: Out of the 939 participants, all-cause mortality at the end of the trial was 50% in the 33°C group (225 of 466 patients) compared with 48% in the 36°C group (235 of 473 patients); the hazard ratio with a temperature of 33°C was 1.06 (95% confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180days, 54% of patients in the 33°C group versus 52% in the 36°C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95% CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180days was unchanged (52%) in both groups (risk ratio 1.01, 95% CI 0.89 to 1.14, P = 0.87). Conclusions: Maintaining targeted lower normothermia of 36°C had similar outcomes compared with induced moderate hypothermia of 33°C for unconscious survivors of OHCA of presumed cardiac cause

Severe Sepsis: A Science of Uncertainty

An evaluation of a recent study by Kaukonen KM, Bailey M, Suzuki S et al: Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012

Alcoholic hepatitis: Yes to prednisolone and no to pentoxifylline [version 1; referees: not peer reviewed]

An evaluation of a recent study by Thursz MR, Richardson P, Allison M et al. " Prednisolone or Pentoxifylline for Alcoholic Hepatitis". N Engl J Med 2015;372:1619-28. PubMed PMID: 25901427. EudraCT number, 2009-013897-42. Current Controlled Trials number ISRCTN88782125

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure: The FLORALI study

An evaluation of a recent study by Frat JP, Thille AW, Mercat A et al: High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure. New England Journal of Medicine 2015;372(23):2185-96. PubMed PMID: 25981908. Clinicaltrials.gov number NCT01320384

The incidence of ventilator-associated pneumonia using the PneuX System with or without elective endotracheal tube exchange: A pilot study

<p>Abstract</p> <p>Background</p> <p>The PneuX System is a novel endotracheal tube and tracheal seal monitor, which has been designed to minimise the aspiration of oropharyngeal secretions. We aimed to determine the incidence of ventilator-associated pneumonia (VAP) in patients who were intubated with the PneuX System and to establish whether intermittent subglottic secretion drainage could be performed reliably and safely using the PneuX System.</p> <p>Findings</p> <p>In this retrospective observational study, data was collected from 53 sequential patients. Nine (17%) patients were initially intubated with the PneuX System and 44 (83%) patients underwent elective exchange to the PneuX System. There were no episodes of VAP while the PneuX System was <it>in situ</it>. On an intention to treat basis, the incidence VAP was 1.8%. There were no complications from, or failure of, subglottic secretion drainage during the study.</p> <p>Conclusions</p> <p>Our study demonstrates that a low incidence of VAP is possible using the PneuX System. Our study also demonstrates that elective exchange and intermittent subglottic secretion drainage can be performed reliably and safely using the PneuX System.</p

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

ObjectiveInhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.Study designA subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.ResultiNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.ConclusioniNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments

Endotracheal tubes and fluid aspiration: An in vitro evaluation of new cuff technologies

© 2017 The Author(s). Background: Aspiration of subglottic secretions past the endotracheal tube (ETT) cuff is a prerequisite for developing ventilator-associated pneumonia (VAP). Subglottic secretion drainage (SSD) ETTs reduce aspiration of subglottic secretions and have demonstrated lower VAP rates. We compared the performance of seven SSD ETTs against a non-SSD ETT in preventing aspiration below inflated cuffs. Methods: ETTs were positioned vertically in 2 cm diameter cylinders. Four ml of a standard microbial suspension was added above inflated cuffs. After 1 h, aspiration was measured and ETTs demonstrating no leakage were subjected to rotational movement and evaluation over 24 h. Collected aspirated fluid was used to inoculate agar media and incubated aerobically at 37 °C for 24 h. The aspiration rate, volume and number of microorganisms that leaked past the cuff was measured. Experiments were repeated (×10) for each type of ETT, with new ETTs used for each repeat. Best performing ETTs were then tested in five different cylinder diameters (1.6, 1.8, 2.0, 2.2 and 2.4 cm). Experiments were repeated as above using sterile water. Volume and time taken for aspiration past the cuff was measured. Experiments were repeated (×10) for each type of ETT. Results were analysed using non-parametric tests for repeated measures. Results: The PneuX ETT prevented aspiration past the cuff in all experiments. All other ETTs allowed aspiration, with considerable variability in performance. The PneuX ETT was statistically superior in reducing aspiration compared to the SealGuard (p < 0.009), KimVent (p < 0.002), TaperGuard (p < 0.004), Lanz (p < 0.001), ISIS (p < 0.001), SACETT (p < 0.001) and Soft Seal (p < 0.001) ETTs. Of the 4 ETTs tested in differing cylinder sizes, the PneuX significantly reduced aspiration across the range of diameters compared to the SealGuard (p < 0.0001), TaperGuard (p < 0.0001) and KimVent (p < 0.0001) ETTs. Conclusions: ETTs showed substantial variation in fluid aspiration, relating to cuff material and design. Variability in performance was likely due to the random manner in which involutional folds form in the inflated ETT cuff. The PneuX ETT was the only ETT able to consistently prevent aspiration past the cuff in all experiments

The Heart Is an Early Target of Anthrax Lethal Toxin in Mice: A Protective Role for Neuronal Nitric Oxide Synthase (nNOS)

Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice causes strikingly increased sensitivity to LT, while deficiencies in the two other NOS enzymes (iNOS and eNOS) have no effect on LT-mediated mortality. The increased sensitivity of nNOS−/− mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nNOS-sufficient wild-type (WT) mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Histopathological analyses showed that LT induced architectural changes in heart morphology of nNOS−/− mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. LT-treated WT mice had no histopathology observed at the light microscopy level. Electron microscopic analyses of LT-treated mice, however, revealed striking pathological changes in the hearts of both nNOS−/− and WT mice, varying only in severity and timing. Endothelial/capillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae were observed in both LT-treated WT and nNOS−/− mice. Furthermore, multiple biomarkers of cardiac injury (myoglobin, cardiac troponin-I, and heart fatty acid binding protein) were elevated in LT-treated mice very rapidly (by 6 h after LT injection) and reached concentrations rarely reported in mice. Cardiac protective nitrite therapy and allopurinol therapy did not have beneficial effects in LT-treated mice. Surprisingly, the potent nitric oxide scavenger, carboxy-PTIO, showed some protective effect against LT. Echocardiography on LT-treated mice indicated an average reduction in ejection fraction following LT treatment in both nNOS−/− and WT mice, indicative of decreased contractile function in the heart. We report the heart as an early target of LT in mice and discuss a protective role for nNOS against LT-mediated cardiac damage