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1.
Procalcitonin as a biomarker for critically ill patients with sepsis: Effects of vitamin D supplementation.
Wolf, TA, Wimalawansa, SJ, Razzaque, MS
The Journal of steroid biochemistry and molecular biology. 2019;:105428
Abstract
Early diagnosis of sepsis is often difficult in clinical practice, whilst it can be vital for positive patient outcomes in sepsis management. Any delay in diagnosis and treatment may lead to significant organ failure and can be associated with elevated mortality rates. Early diagnosis and effective management of sepsis can allow for prompt antibiotic therapy and a potential reduction in mortality; it can also minimize the unnecessary use of antibiotics. Furthermore, vitamin D supplementation, which is commonly used in the intensive care units to reduce mortality, may interfere with the ability to use procalcitonin (PCT) as a means of assessing clinical progression. This paper aims to explore the diagnostic and prognostic value of serum levels of PCT as an early marker of sepsis and to assess whether it can be used as a guide for using antibiotic therapy. Several serum-based biomarkers such as C-reactive protein, lactate, presepsin, and cytokines, such as interleukin-1 (IL-1), and IL-6 have been evaluated as early indicators of sepsis but none have been proven sensitive and/or specific enough to make a definitive diagnosis. Finally the potential benefits and disadvantages of using serum levels of PCT to diagnose and monitor patients with sepsis and septic shock will be briefly discussed.
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2.
Mitochondria in Sepsis-Induced AKI.
Sun, J, Zhang, J, Tian, J, Virzì, GM, Digvijay, K, Cueto, L, Yin, Y, Rosner, MH, Ronco, C
Journal of the American Society of Nephrology : JASN. 2019;(7):1151-1161
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Abstract
AKI is a common clinical condition associated with the risk of developing CKD and ESKD. Sepsis is the leading cause of AKI in the intensive care unit (ICU) and accounts for nearly half of all AKI events. Patients with AKI who require dialysis have an unacceptably high mortality rate of 60%-80%. During sepsis, endothelial activation, increased microvascular permeability, changes in regional blood flow distribution with resulting areas of hypoperfusion, and hypoxemia can lead to AKI. No effective drugs to prevent or treat human sepsis-induced AKI are currently available. Recent research has identified dysfunction in energy metabolism as a critical contributor to the pathogenesis of AKI. Mitochondria, the center of energy metabolism, are increasingly recognized to be involved in the pathophysiology of sepsis-induced AKI and mitochondria could serve as a potential therapeutic target. In this review, we summarize the potential role of mitochondria in sepsis-induced AKI and identify future therapeutic approaches that target mitochondrial function in an effort to treat sepsis-induced AKI.
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3.
Safety of vitamin C in sepsis: a neglected topic.
Khoshnam-Rad, N, Khalili, H
Current opinion in critical care. 2019;(4):329-333
Abstract
PURPOSE OF REVIEW Although vitamin C is essentially a nontoxic vitamin; however, it is important to be aware regarding the safety of high doses before the wide clinical use. RECENT FINDINGS Minor side effects of vitamin C have been reported, many being reported in earlier studies. High doses of vitamin C (up to 1.5 g/kg three times a week as intravenously) were safe in cancer patients with normal renal function and perfect glucose-6-phosphate dehydrogenase activity. As the dose and duration of administration of vitamin C in sepsis are lower and shorter than those used in cancer patients, it seems that it is relatively safe for this population. In ongoing trials, safety of high doses of vitamin C is considered. SUMMARY Data regarding the safety of high doses of vitamin C are scant. Until more data become available, caution should be applied in the use of high doses of vitamin C in patients with hemochromatosis, glucose-6-phosphate dehydrogenase deficiency, renal dysfunction, kidney stone, oxaluria, and pediatrics.
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Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation.
Moskowitz, A, Andersen, LW, Huang, DT, Berg, KM, Grossestreuer, AV, Marik, PE, Sherwin, RL, Hou, PC, Becker, LB, Cocchi, MN, et al
Critical care (London, England). 2018;(1):283
Abstract
The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.
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Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis.
He, Y, Cao, L, Yu, J
Medicine. 2018;(35):e11976
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Abstract
BACKGROUND Currently, prophylactic use of drugs to promote a healthy gut microbiota and immune system in preterm infants is hot debated, among which lactoferrin is a promising supplementation. However, the effect and safety of lactoferrin to prevent late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants remains controversial. METHODS Databases including Medline, Ovid-Embase, The Cochrane Library, CBM, CNKI, and VIP database of Chinese Journal were searched to collect randomized controlled trials (RCTs) about lactoferrin for preventing LOS and NEC in preterm infants. Languages of included RCTs were restricted to English and Chinese. Meta-analysis was conducted by Rev Man 5.3 software. The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS A total of 9 RCTs, involving 1834 patients, were included. Pooled analysis showed that prophylactic lactoferrin could significantly reduce the incidence all culture-proven LOS (41/629 [6.5%] vs 96/659 [15.3%]; RR 0.47; 95% CI 0.33-0.67; P < .01) and NEC (stage II or more) (9/448 [2.0%] vs 26/462 [5.6%]; RR 0.40; 95% CI 0.18-0.86; P < .01). Lactoferrin was also associated with a significantly decreased hospital-acquired infection (16/139 [11.5%] vs 35/140 [25%]; RR 0.47; 95% CI 0.27-0.80; P < .01); and infection-related mortality (4/474 [0.8%] vs 25/505 [4.9%]; RR 0.24; 95% CI 0.04-1.32; P < .01, I = 53%). Lactoferrin could shorten time to reach full enteral feeding (weighted mean difference [WMD] = -2.11, 95% CI -3.12 to -1.10; P < .01) and showed a decreasing trend of duration of hospitalization (WMD = -1.69, 95% CI -6.87 to 3.50; P < .01; I = 95%). Lactoferrin did not have a significant effect on all-cause mortality (22/625 [3.5%] vs 35/647 [5.4%]; RR 0.70; 95% CI 0.38-1.30; P = .16; I = 13%). None of the included trials reported any confirmed adverse effects caused by the supplemented lactoferrin or probiotics. CONCLUSION Current evidence indicates that lactoferrin could significantly reduce the incidence of NEC and LOS, and decrease the risk of hospital-acquired infection and infection-related mortality in premature infants without obvious adverse effects.
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Applications of vitamin D in sepsis prevention.
Takeuti, FAC, Guimaraes, FSF, Guimaraes, PSF
Discovery medicine. 2018;(140):291-297
Abstract
Vitamin D (VD) is a steroid prohormone that regulates the body's calcium and phosphate levels in bone mineralization. It is also well described as a fat-soluble vitamin playing an important role in immunomodulation, regulation of cytokines, and cell proliferation. Thus, VD is a powerful hormone with pleiotropic effects, which acts to maintain optimal health. Recent studies demonstrate that VD deficiency is associated with the development of cardiovascular diseases, autoimmune disorders, and various types of cancer, each associated with increased mortality rates. VD deficiency is commonly seen in the intensive care unit (ICU); it aggravates the incidence and outcome of infectious complications in critically ill patients. In particular, VD deficiency is associated with an increased risk of sepsis and more severe clinical outcomes in patients with sepsis. These patients have dysregulated VD metabolism and frequently present insufficient plasma VD levels, which contribute to the deterioration of their clinical state. In this review, we summarize the role of VD in the immune system, the consequences of its deficiency and we discuss potential perspectives on VD supplementation in preventing sepsis and enhancing patient recovery. Although the relevance of the applications of VD in sepsis is stated, further studies are required to elucidate the optimal VD plasma levels and the recommended daily intake.
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Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid.
Marik, PE
Nutrients. 2018;(11)
Abstract
Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents that targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents, which target multiple components of the host's response to an infectious agent, will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.
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New insights into the gut as the driver of critical illness and organ failure.
Meng, M, Klingensmith, NJ, Coopersmith, CM
Current opinion in critical care. 2017;(2):143-148
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Abstract
PURPOSE OF REVIEW The gut has long been hypothesized to be the 'motor' of multiple organ dysfunction syndrome. This review serves as an update on new data elucidating the role of the gut as the propagator of organ failure in critical illness. RECENT FINDINGS Under basal conditions, the gut absorbs nutrients and serves as a barrier that prevents approximately 40 trillion intraluminal microbes and their products from causing host injury. However, in critical illness, gut integrity is disrupted with hyperpermeability and increased epithelial apoptosis, allowing contamination of extraluminal sites that are ordinarily sterile. These alterations in gut integrity are further exacerbated in the setting of preexisting comorbidities. The normally commensal microflora is also altered in critical illness, with increases in microbial virulence and decreases in diversity, which leads to further pathologic responses within the host. SUMMARY All components of the gut are adversely impacted by critical illness. Gut injury can not only propagate local damage, but can also cause distant injury and organ failure. Understanding how the multifaceted components of the gut interact and how these are perturbed in critical illness may play an important role in turning off the 'motor' of multiple organ dysfunction syndrome in the future.
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[Probiotics: innocuousness, prevention and risks].
Brunser, O
Revista chilena de pediatria. 2017;(4):534-540
Abstract
Probiotics have been defined as live microorganisms which, when ingested in adequate numbers, confer health benefits to the host. They are currently consumed without any age restrictions and adverse effects such as sepsis, a marker of the risk of invasion of the bloodstream, are extremely infrequent. However, some health professionals express doubts about probiotics being truly innocuous. This review discusses the incidence of sepsis secondary to probiotics use, mainly lactobacilli and bifidobacteria, evaluated through molecular biology or classic culture techniques, showing that sepsis in large numbers of individuals along decennia is extremely low, of the order of 0,02% en some centers or as low as 1 case/million population in France. These data are important considering the use different species and strains of these microorganisms. Few studies which have reported other adverse effects but many of these have problems with their design that cast doubt about the validity of their results. On the contrary, it has been shown that probiotic microorganisms exert positive stimulatory effects on innate and acquired immunity, with decrease of the manifestations of atopy and eczema. These positive effects are further evidenced by the beneficial effects of many species of probiotics in preventing necrotizing enterocolitis in patients as functionally labile as premature-born babies.
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Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis.
Silversides, JA, Major, E, Ferguson, AJ, Mann, EE, McAuley, DF, Marshall, JC, Blackwood, B, Fan, E
Intensive care medicine. 2017;(2):155-170
Abstract
BACKGROUND It is unknown whether a conservative approach to fluid administration or deresuscitation (active removal of fluid using diuretics or renal replacement therapy) is beneficial following haemodynamic stabilisation of critically ill patients. PURPOSE To evaluate the efficacy and safety of conservative or deresuscitative fluid strategies in adults and children with acute respiratory distress syndrome (ARDS), sepsis or systemic inflammatory response syndrome (SIRS) in the post-resuscitation phase of critical illness. METHODS We searched Medline, EMBASE and the Cochrane central register of controlled trials from 1980 to June 2016, and manually reviewed relevant conference proceedings from 2009 to the present. Two reviewers independently assessed search results for inclusion and undertook data extraction and quality appraisal. We included randomised trials comparing fluid regimens with differing fluid balances between groups, and observational studies investigating the relationship between fluid balance and clinical outcomes. RESULTS Forty-nine studies met the inclusion criteria. Marked clinical heterogeneity was evident. In a meta-analysis of 11 randomised trials (2051 patients) using a random-effects model, we found no significant difference in mortality with conservative or deresuscitative strategies compared with a liberal strategy or usual care [pooled risk ratio (RR) 0.92, 95 % confidence interval (CI) 0.82-1.02, I 2 = 0 %]. A conservative or deresuscitative strategy resulted in increased ventilator-free days (mean difference 1.82 days, 95 % CI 0.53-3.10, I 2 = 9 %) and reduced length of ICU stay (mean difference -1.88 days, 95 % CI -0.12 to -3.64, I 2 = 75 %) compared with a liberal strategy or standard care. CONCLUSIONS In adults and children with ARDS, sepsis or SIRS, a conservative or deresuscitative fluid strategy results in an increased number of ventilator-free days and a decreased length of ICU stay compared with a liberal strategy or standard care. The effect on mortality remains uncertain. Large randomised trials are needed to determine optimal fluid strategies in critical illness.