Sepsis - Science topic

Thank you, @ ,Beth Ann Fiedler ,Beth Ann Fiedler your information on this life-threatening emergency in developed and developing countries is apt. The threat of antimicrobial resistance in developing countries and upsurge of patients with pneumonia, UTI, malnutrition, immunodeficiency related diseases just to mention but a few coming down with sepsis is alarming. Sepsis is an important public health challenge, therefore creation of massive awareness Campaign on sepsis, and partnership with public health professionals, clinical experts, patient's advocacy groups and the public will cause more people to survive sepsis or avoid it entirely.

It sounds like a retrospective cohort study.

Hi, in our practise we routinely do Urine CS one week before PCNl if positive start antibiotics. If urgent need of surgery and patient is asymptomatic TLC is normal, even with urine CS positive we do PCNL with atheist few dose of preoperative antibiotics.

During surgery we do give antibiotics at the time of induction of surgery.

And at the time of stone breaking we guve one dose of amikacin along with lasix.

Post operative we do give antibiotics as required till discharge.

Of Pus during initial puncture we keep PC N for drainage and do surgery later

Thanx

Wrong anesthetic practice

I think you need to consider the surgical procedure especially the anaesthetic agent. Using ketamine with xylazine combination need to adjust carefully.

Personally, based on my experience with surgical procedures in mice, I prefer using an inhalation anaesthesia agent.

You can read more :

You can acquire SSI within 3 months of surgery.

It's seems different,

Maybe this article help understanding of it and finding some facts direct you to the right answer

https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2529993X19302357&r=428

The general role in estimating prevalence is dividing the outcome of interest or an event (old or new) over the population group of interest at a specific period of time. Therefore, the sample size shoud be calculated out of the particular population of interest.

Elevated PCT (procalcitonin) levels are positively associated with the severity of COVID-19.

I think you might be looking for this sort of thing;

Lactate levels are good predictors of mortality in patients with sepsis

use the following equation

I am eager to know that, in my country, I haven't seen it

i think need to follow fluid requirements

Joyeeta Mitra

Did you ever find good resources? I'm looking for the exact same thing actually. Thank you in advance if you can send links for some materials!

https://www.cureus.com/articles/27924-coronavirus-covid-19-a-review-of-clinical-features-diagnosis-and-treatment

Immunosuppression in sepsis is a real problem and very individual. Epigentic and metabolic reporgramming as well as the chronic release of DAMPS during the course of sepsis influence immunosuppression. The high prevalence of secondary viral infection (e.g. EBV, CMV) is one result of these processes. You might also find this articel informative.

This question is debated for decades and you find plenty of literature for both standpoints. In my opinion you should treat a severe hypoalbuminemia (<20g/l) in fluid-resistant hypotension. You might also want to follow up the ongoing ARISS trial (NCT03869385).

Hi, This is a very interesting and relevant question for the entire research community working in metabolomics. Please feel free to register (for free to create a login with your Email ID!) and join the International Metabolomics Society’s Forum: http://www.metabolomics-forum.com/index.php?action=forum;?action=forum#c12 to ask more specific questions any software, database, approach and platform (mass spectrometry, NMR) issues where you can get very specific responses from expert users and researchers! Thanks again, Biswa

many thanks, Markus and Aldo

I found that PEGylation prolongs the circulation time of proteins by decreasing the kidney filtration. PEGylation also increases the stability of proteins and decreases the immunogenicity of proteins, so I believe it is more appropriated for therapeutic than for immunization purposes.

We the non physician grs should nicely enjoying the discussion regarding SEPSIS-

A great cause of death . I specially thanks to Dr.Janeena Ieraci & Dr.Md Rabiul Alam

for technicalities of sepsis like EHR & qSOFA .

I have observed in recent years that critically ill patients in the ICU are sometimes maintained on mechanical hyperventilation with propofol sedation. ln my opinion, this is harmful and counterproductive. All hypnotics are inherently toxic, including anesthetic inhalation agents. The toxicity of propofol is notorious. George Washington Crile described how he cured sepsis and peritonitis 100 years ago when primitive needle technology made intravenous access impractical. He used massive doses of intramuscular morphine that caused his patients to become essentially comatose for up to a week, without the help of intravenous fluids or even antibiotics. This cured cases of sepsis and peritonitis. Crile had discovered the nervous component of what was then called "shock". He describes his discoveries and treatment strategies in his famous book called "Anoci-association" that can be accessed free of charge via the Internet. With our modern machines, medications and monitors we can do better. We can safely maintain deliberate high levels of "permissive hypercarbia" that offsets the respiratory depression caused by modern synthetic opioids; the combination works like love and marriage. Hypercarbia optimizes cardiopulmonary performance and enhances the release of oxygen from the hemoglobin molecule, and therefore optimizes tissue oxygenation. This is helpful in all forms of sepsis and especially helpful in stubborn cases of infestation with "facultative anaerobes" that proliferate in poorly perfused and oxygenated tissues where antibiotic "penetration" is limited, such as Lyme Disease, MRSA and so forth. Last, but not least, non-toxic opioid supplementation reduces reliance on toxic hypnotic agents. The best choice for a hypnotic agent is anesthetic inhalation agents, which can be maintained at precise levels, adjusted quickly, and rapidly rid from the body. These principles could revolutionize the care of critically ill patients if they were fully utilized.

Yes. But you could ask to them to lend you a magnet if you don't have one already. They tend to do that.

If you think your selected topic has already been done then why on earth would you want to pursue it? Meta-analysis is a design used to answer a gap in knowledge and if that gap does not exist then why do you still want to pursue a meta-analysis? A new meta-analysis should only be undertaken if a gap in knowledge exists and you believe you have the expertise to undertake a meta-analysis whose purpose is to conclusively answer a critical question.

Surviving Sepsis guidelines are clear on definitions in sepsis and septic shock. However, bundle in sepsis is the best strategy for our patients.

Why are you using LPS isolated from different bacteria?

Even LPS isolated from different stains of E.coli will have differences in activation/stimulation of immunity.

You can buy LPS from E.coli O111;B4 from Sigma too.

If silk was used while closing the fascia, it may cause a local and sometimes systemic reaction. A granulation tissue may adsorb the silk threads and within time the granulation tissue drains to skin and this is how you see threads many times after the surgery

This is the fundamental. All other details you can find from the literature at the end of manuscript.

take a look at Mc Allen RM, AJP, last paper in AJP

THE ANTI-INFLAMMATORY REFLEX ACTION OF THE SPLANCHNIC SYMPATHETIC NERVES IS DISTRIBUTED ACROSS ABDOMINAL ORGANS.

Martelli D, Farmer DG, McKinley MJ, Yao ST, McAllen RM.

Am J Physiol Regul Integr Comp Physiol. 2018 Dec 21. doi: 10.1152/ajpregu.00298.2018. [Epub ahead of print]

PMID: 30576218

Similar articles

This may help. Best. LQ.

@

Hi

For sample size calculation you will need what is the current incidence of sepsis and what amount of changes you are expecting from the intervention. You can go for both randomized and non-randomized design. In the sample size calculation, you have decide how much absolute precision (1-alfa) and power (1-beta) you want. Usually, absolute precision of 5% and power of 80% is acceptable lower limit. If your trial is non-randomized, it is better to put a design effect. You can use online free statistical site www.openepi.com for this.

For analysis, it depends on the data. but from your objective, it appears that you will require unpaired t-test, Fisher's exact/Chi-square test. You can also calculate the sensitivity and specificity if the intervention is diagnostic and calculate the area under the curve for all interventions. For this you have to have one gold standard (these tests will be required if intervention is diagnostic only). At present statistical software also prompts what tests are appropriate provided you enter the data type correctly.

Hope this helps you

The yield of the cultures with blood or plasma is better than with serum. The same applies to molecular diagnostics with better yield from plasma as compared to serum. The yield is poor with serum.

https://www.researchgate.net/search.Search.html?type=publication&query=%D0%97%D0%B0%D0%B1%D1%80%D0%BE%D0%B4%D1%81%D0%BA%D0%B8%D0%B9%20%D0%9F.%20%D0%A4.,%20%D0%9C%D0%B0%D0%BD%D0%B4%D1%8B%D1%87%20%D0%92.%20%D0%93.%20%D0%98%D0%BC%D0%BC%D1%83%D0%BD%D0%BE%D1%82%D0%BE%D0%BA%D1%81%D0%B8%D0%BA%D0%BE%D0%BB%D0%BE%D0%B3%D0%B8%D1%8F%20%D0%BA%D1%81%D0%B5%D0%BD%D0%BE%D0%B1%D0%B8%D0%BE%D1%82%D0%B8%D0%BA%D0%BE%D0%B2.%20%E2%80%94%20%D0%A1%D0%B0%D1%80%D0%B0%D1%82%D0%BE%D0%B2:%20%D0%98%D0%B7%D0%B4-%D0%B2%D0%BE%20%D0%A1%D0%92%D0%98%D0%91%D0%A5%D0%91,%202007.%20%E2%80%94%20420%20%D1%81.%20%E2%80%94%20ISBN%20978-5-91272-254-7.

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I agree with Dr.Evers .

Good proposal, I hope you find answer, you can check the following

Nice read, I agree with some previous comments, I liked that reference #13- year 2014 artcile with comprehensive review - Catia Cillóniz Ian Ewart

Linus Pauling who won the Nobel Prize twice wrote a book on Vitamin C and suggested that we take at least 4,000 mg a day. I have been taking 3,000 a day for the past 20 years and seldom do I get sick! Amir

Agree with Hans-Dieter Volk. In contrast to murine endotoxaemia, in human no standardization may be achieved. We had several studies of LPS, EndoCAb, cytokines, and apoptosis markers as well, etc. in both humans and rats. Comparing is difficult as humans have disease status when raised LPS is only a part of condition, while in rodents we use industry made LPS with standardized source, activity, etc. PCT, lactate, total cholesterol or other markers are useless when trying to achieve direct effect of LPS. Furthermore, LPS-binding protein influences the pro-apoptotic effect of LPS multiple times. Same levels of serum LPS under different conditions (for example, sepsis, IBD or fatty liver disease in our studies) cause different levels of apoptosis.

the link is mainly related to effect of the microbiome, but some clues

check the ORACLES studies on maternal antibiotics to delay preterm birth in mothers with or without ruptured membranes.

on neonates, some recent meta-analyses:

Reviewing the WHO guidelines for antibiotic use for sepsis in neonates and children.

Fuchs A, Bielicki J, Mathur S, Sharland M, Van Den Anker JN.

Paediatr Int Child Health. 2018 Nov;38(sup1):S3-S15

Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C.

J Antimicrob Chemother. 2017 Jul 1;72(7):1858-1870.

What you're proposing isn't a part of any research here formally,but has been highlighted yet again in the UK news recently where the family of a child with sepsis were not only the first to realise,but tried on several occasions to get appropriate care.

Family involvement could clearly play an increasing role in early diagnosis and management of sepsis.

Good luck.

yes you can join our research .but what is the type of patrticipation you can share us?

Thanks.

Hi Ian, many thanks!

Honestly, I was absolutely smitten as why I could not find any reference to serum insulin levels. However, that there is in fact not many publications on this topic is even stranger though...

In any case, articles definitely seem relevant. Will most certainly have a closer look -thanks!

this study was conducted with patients of aged median (5th and 95th percentiles) of 63 (6 -70) years found that in spontaneously breathing patients with ACF, high cIVC values (>40%) are usually associated with fluid responsiveness while low values (< 40%) do not exclude fluid responsiveness

IVC collapsibilty index measured by ultrasound is useful for the detection of early intravascular volume change induced by 2 min passive leg raising. However, its ability to detect the increased Intravascular volume value is influenced by age, BMI, and baseline CI. Moreover, they found poor sensitivity.

As vascular calcification is common in elderly, it may affect the collapsibility and therefore a hypothesis that elderly population may respond differently is possible and will require further direct research.

The aim of perioperative antibiotics is prophylaxis of infection caused by surgical trauma. If you are performing craniotomy, you need antibiotics against skin pathogens (e.g staphyloccocus), by urogenital surgery against typical uro bacteria, (e.g for E.coli Ciprofloxacine).

If you have other source of infection and antibiotic therapy you need to check, if your antibiotic therapy is effective for the bacteria on your surgical site.

Secondly, the timing of antibiotics before surgery is crucial. Before your incision, you need effective dosis of antbiotics in your surgical site. 30-60 Minutes before incision is the recommendation.

In Your case I would suggest:

mostly the therapy plan of meropenem doesn´t match with time of surgery, you do not have guarantee for the peak level of antibioticasin your surgical site. I would suggest the additional dose of cephalosporine (eg. Cephazoline) 2g (in 10ml Saline). You give 1 ml testdosis the check allegic reaction, than the rest. The timing 30-60 before incision.

If the surgery takes longer than 4 hours, you give the second dose.

at the day of surgery you give one dosis cephalosporins at night after surgery and the last one the next day. You have very good effectivness of cephalosporines against staphylococcus.

I think intraperitoneal administration is easier to achieve from the perspective of compound solubility and injection volume. IV administration requires that the compound be dissolved, and limits the injection volume. For a compound with poor solubility, IV may be not allow a sufficient quantity of the compound to be administered in a single dose. Another option, is IV infusion, in which the dose is delivered by an infusion pump over several hours, allowing a larger volume/more dilute solution, and therefore greater exposure to the compound.

I am going to send you several studies from Manu Malbrain and colleagues, from which I first heard for CRP/Alb ratio or CLI (capillary leak index). They have an idea of resuscitation and deresuscitation in septic shock. I think this will help you a little bit. Anyway, good idea which should be investigated and spread.

PS. I tried....it works if the time is correct.

It is controversial if controlling fever can affect patients' outcome. Apart from specific subgroups (Neuro, IHD where tachycardia can induce ischemia). Moreover, in sepsis, we monitor response to antimicrobials by monitoring the temperatur. So, and in order to avoid the undesirable NSAIDs, I think paracetamol in general is more than enough.

Hi, try with mitomycin C plus irinotecan, or with regorafenib or pemetrexed. You can find several phase II trials suporting this therapies. 

Dear Sagar,

Your problem is likely EDTA, try Heparin as the anticoagulant instead, this usually works fine. No need to place the cells in culture media, the blood is a rich source of everything they need. Best regards Christoph

Komal, 

Ceftriaxone is inactive against most strains of Pseudomonas aeruginosa, many strains of Enterobactor cloacae and methicillin resistant strains of staphylococci. This is the primary reason to utilize dual therapy. 

Regards,

Christopher

One way to approach the topic is as folllows:

1.  define sepsis rigorously

2.  separate sepsis from other types of infections in diabetic elderly patients

3.  you may want to separate sepsis into 2 groups:

3.1  septic elderly diabetic patients "who require intensive unit care vs.

3.2  septic elderly diabetes patients" "who are treat on a hospital ward."

Please let me know if the following references/sites are helpful to you:

1.  Severe sepsis and septic shock in the elderly: An overview

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956061/Feb 4, 2012 ... The elderly are predisposed to sepsis due to co-existing ... as cancer, diabetes, obesity, and human immunodeficiency virus, among others[6].

2.  Sepsis Linked to Dementia in Elderly - WebMD

http://www.webmd.com/healthy-aging/news/20101026/sepsis-linked-to-dementia-in-elderlyOct 26, 2010 ... Oct. 26, 2010 -- Sepsis is a leading cause of death in hospital ICUs, and the elderly are particularly vulnerable to the life-threatening blood ...

3.  Sepsis Requires Urgent Attention - Today's Geriatric Medicine

http://www.todaysgeriatricmedicine.com/archive/050613p26.shtmlThey know about heart attack, stroke, diabetes but not sepsis.” ... nearly normal in an elderly patient, preventing the connection to sepsis from being obvious.

4.  Sepsis in Elderly Patients - Nursing Home Abuse Guide

http://www.nursinghomeabuseguide.org/injuries/sepsis-in-elderly-patients/Anyone who has an elderly loved one as well as anyone who works in a nursing home must know the signs of sepsis so that it can be recognized as quickly as ...

5.  Sepsis Symptoms, Treatment, Causes - What are sepsis (blood

...

http://www.medicinenet.com/sepsis/page5.htmMar 8, 2017 ... What are sepsis (blood poisoning) symptoms and signs? ... The very young and the elderly are at greatest risk; People who are very ill due to an ... Diabetes: Tips for Managing Glucose Levels and Blood Sugar Swings.

Dennis

Dennis; Mazur

Hello

Hope these links help you 

Good Luck 

George C. Kramer of UTMB is working on similar projects. Try to contact him at https://www.researchgate.net/profile/George_Kramer3 in Research Gate. If he is not answering (your message can get lost in the multitude of the RG communications), I can ask him for permission to give you his direct email.

Dear Antonio,

are you looking for something like

Best regards

Matthias

Start with a September 2010 nature reviews paper by Martin et.al. omega-3 fatty acids in critical illness 

I think Medscape is so helpful (link below)

Hi Diego. What a good idea!  I have not done DNA extraction from such material, in fact in my google scholar search I could find no reference to it. However, I suggest good starting point for this work would be to test kits that are suitable for blood, serum, stool and/or food.  In particular, there are several papers concerning extraction of bacterial DNA from milk. Some of the methods/kits for food will have more mechanical and enyzmatic digestion required for your samples.

Almost certainly a column based method will be appropriate.  If you have the money, it's worth checking out Qiagen kits - whenever I have used them I got good results.  If you have a chat with the technical help people at the companies that make the DNA extraction kits I am sure they will be very helpful, and possibly even supply you with free samples.  

Here are a few articles to give you some ideas:

Best regards

Roger Latham

Based on meta-analyses (eg, Vasu, J Intens Care Med 2012) and the SOAP II trial (De Backer, NEJM, 2010), we prefer norepinephrine over dopamine in shock.

ursodeoxycholic acid is a  chelator of bile acids, has cytoprotective and immunomodulatory effects, it has been used to treat cholestatic diseases .it could be considered for sepsis-induced cholestasis , but no data currently support such an assertion.

What happened to piperacillin/tazobactam sensitivity?

The use of carbapenems agains these urinary pathogens is risky, as you can see with the most recent antibiogram.

The first step when we face against multiresistant urinary gram negative bacteria is to separate infection from colonization. In case of infection, we must define if it's confined to lower urinary tract (aka cystitis) or if we have bacteriemia. In cystitis, due to an extraordinary multiplication of urinary concentrations, even in vitro resistant antibiotics may work in vivo. It happens for TMP-SMX, nitrofurantoine and norfloxacin.

For urinary sepsis our last weapon in Portugal is IV colistin. Off label, in my hospital, we use sometimes intravesical colistin: no systemic side effects and good results in eradicating MR Klebsiella, providing no sepsis is suspected.

Dear Martin,

The following recent review article entitled " Absolute and Relative Contraindications to IV rt-PA for Acute Ischemic Stroke" published in Neurohospitalist. 2015 Jul; 5(3): 110–121 may shed light on the use of IV rt-PA for Acute Ischemic Stroke:

Most of the contraindications to the administration of intravenous (IV) recombinant tissue plasminogen activator (rtPA) originated as exclusion criteria in major stroke trials. These were derived from expert consensus for the National Institute of Neurological Disorders and Stroke (NINDS) trial. Despite the fact that the safety and efficacy of IV rtPA has been repeatedly confirmed in large international observational studies over the past 20 years, most patients with acute ischemic stroke disappointingly still do not receive thrombolytic treatment. Some of the original exclusion criteria have proven to be unnecessarily restrictive in real-world clinical practice. It has been suggested that application of relaxed exclusion criteria might increase the IV thrombolysis rate up to 20% with comparable outcomes to thrombolysis with more conventional criteria. We review the absolute and relative contraindications to IV rtPA for acute ischemic stroke, discussing the underlying rationale and evidence supporting these exclusion criteria.

Hoping this will contribute to the discussion on this very important issue.

Rafik

Hello Omar,

It's an interesting thought. One could use Hydrex - 0.5% Chlorhexydine with 70% alcohol - to prepare the skin although I suspect one would need to prep the entire foot to be sure. I don't see why not but as an exception as opposed to as standard, as the risk of false-positive would be higher - one can test that in a study of course. However, it would be hard to maintain the same rigour of antiseptic cleansing in "real life" compared to study conditions. Let me know how you get on with it, cheers, Art

Fever should be treated only when it is higher than 41 celcius, or when it is causing symptomatic disturbance to the patient like diaphoresis, anxiety, tachypnea, tachycardia and/or hypotension. However we use antipyretics only as needed, not in a long term basis as fever is an important sign to follow the response to treatment or to identify the presence of a new infection or resistance to treatment. 

The HETRASE trial randomly assigned 319 patients with sepsis to receive low dose intravenous heparin (500 units per hour) or placebo for seven days. The trial found no improvement in any clinical outcome. It has been suggested that the conflicting results were due to the randomized trial using a low dose of heparin; as a result, a randomized trial comparing various doses of heparin in patients with septic shock is being conducted:  http://www.clinicaltrials.gov/ct2/show/NCT01234285

Dear Michaela Yakubovich-Dirks ,

Sorry for delay to see your question or doubt, I´m reffering to any transplantation with prognosis risk of rejection experienced.

I think the question refers to treatment with glucosamine or another agent to make the mouse more sensitive to LPS (endotoxin). Mice can tolerate mg of LPS, while humans become ill (fever, etc) with doses in ng/kg.

I agree to Roop Kishan. Close clinical monitoring of patient with impending sepsis teaches you a lot than following the algorithms and score.Of course scores and algorithms have their own place for follow up management of sepsis.

.....Endotoxin release is episodic and circulating LPS has a short half-life (minutes), obscuring the value of a single determination. In the bloodstream, LPS is distributed in varying proportions bound by LBP, micelles, chylomicrons, and various other lipid fractions; some of these bound moieties are biologically inactive, but most assays measure all LPS whether biologically active or not—again, making the relevance of the results uncertain.

.....The susceptibility of different animal species to the toxicity of lipopolysaccharide (LPS) is highly variable.

Most strains are OK to use, but you should avoid using the C3H/HeJ mouse strain as it has a mutation in TLR4 making it non-responsive to LPS treatment.

Measuring GCS in the sedated population can lead to incorrect SOFA scoring, even in those patients receiving a daily drug "holiday". The lingering effects of sedatives can decrease perceived/measured mentation. So, my answer is, that there is no easy way to address this precisely. We try to assess prior to sedation, when able, then continue with this score until off sedation for an adequate period of time to clear sedative effects.

The E. coli: O111:B4 is the best characterized   

LPS is well tolerated by rodents, dogs and cats (Warren et al., 2010), but it is very dangerous for humans, causing septic shock (Yamamoto et al., 2011). Rodents are 1000-10000 less sensitive than humans due to special LPS binding proteins, but I do not know, if everything is clarified. 

Warren TS, Fitting C, Hoff E, Adib-Conquy M, Beasley-Topliffe L, Tesini B, et al. Resilience to bacterial infection: difference between species could be due to proteins in serum. J Infect Dis. 2010;201:223-32.   

Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, et al. Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol. 2011;186(5):3248-57.  

Dear Khan,

Please read the followings:

1-A single injection of endotoxin, or LPS, is the most commonly used toxemia model. Compared with humans, laboratory animals appear relatively insensitive to LPS and, therefore, require higher doses of LPS to produce a shock-like state. In a study directly comparing the effects of LPS, the dose required to produce similar cytokine responses was 250 times higher in mice than in humans.16 A single dose of LPS (approximately 2 ng/kg) could produce profound physiologic effects in humans (for example, increases in body temperature, systolic blood pressure, and heart rate), whereas similar signs were not seen in mice despite a much higher dose of LPS (500 ng/kg).16 The amount of LPS used to produce systemic signs in murine models varies widely, depending on the origin of LPS and mouse strain, but doses of approximately 10 mg/kg or higher are not atypical. Alternatively, doses may be reduced by sensitizing animals to LPS by coinjection of D-galactosamine.11

for more details, please use the following link:

2-Compared with humans, mice, even “normally responsive” strains, are remarkably less sensitive to the toxic or lethal effects of LPS. Thus, the dose of LPS, which leads to death in approximately half of mice (i.e., the LD50 dose) is about 1–25 mg/kg.37-39 This dose is about 1 000 000 times greater than the typical dose of LPS (2–4 ng/kg), which has been used in studies with human volunteer to induce symptoms (e.g., fever or myalgia) and the release of proinflammtory cytokines, such as TNF, into the circulation.40,41 The LD50 dose of LPS in mice is about 1000-fold to 10 000-fold greater than the dose of LPS that is required to induce severe illness and hypotension in humans.42 In other words, the roughly 40-fold difference in the dose of LPS that is required to produce toxicity or death in “normally responsive” vs. “hyporesponsive” strains of mice is orders of magnitude smaller than is the difference in LPS dose that is required to produce death or serious illness in “normally responsive” mice as compared with human beings. The biological mechanism(s) that are responsible for the enormous difference between mice and humans with respect to responsiveness to LPS remain to be fully elucidated, but recent evidence obtained by Warren and colleagues suggests that one or more factors, which are present in murine sera, but are absent (or present in much lower concentrations) in human sera, are capable of suppressing the production of pro-inflammatory cytokines by murine (or human) mononuclear cells following stimulation with LPS or other TLR agonists, such as peptidoglycan (major component of the cell wall of gram-positive bacteria), zymosan (a glucan present in the cell wall of yeast) or bacterial DNA.43 One of these factors may be the iron-binding acute phase protein, hemopexin.44 Other factors, which have yet to be identified, may be important as well. In any event, the marked discrepancy in LPS sensitivity between mice and people suggests that data obtained using murine models of sepsis may be inapplicable to the human illness.

For more details, please use the following link:

Hoping this will be helpful,

Rafik

How do I diagnose sepsis (being an infection with systemic features and evidence of organ impairment)? - this is a clinical/laboratory diagnosis which combines clinical features of inflammation (fever, tachycardia, diaphoresis, apparent focus of infection) with laboratory parameters (white cell count, neutrophil count, C-reactive protein, pro-calcitonin), and where appropriate radiological evidence of a focus (CXR -pneumonia, CT abdomen -intra-abdominal collection etc...).  Ideally one also takes appropriate samples for microbiological testing, either by culture, molecular testing or serology.  The firmest diagnosis is based on a combination of clinical, laboratory, radiological and microbiological results, where all point in the same direction.  If you are specifically interested in blood stream infections, then detection of the organism of interest in the blood is the key, as blood stream infections do not generally have focal signs  (that being said a pure 'bacteraemia' without primary source is pretty rare - most bacteraemias arise from a reservoir of infection such as the lung, abdomen/renal tract, intravascular line or heart valve).

The problem is that no single one of these tests and clinical features is either very sensitive nor very specific for sepsis - they may be absent in the presence of sepsis and equally may be present when there is no sepsis.  This is why it requires an integration of multiple data sources to make the diagnosis.  PCT has been touted as a specific and sensitive test for bacterial infection, however it is not sensitive to all bacterial infections and fails to account for non-bacterial infections - its best use is probably in helping limit antibiotic therapy duration.

There are novel diagnostics either close to or on the market - the wider range of molecular diagnostics will make it easier to detect organisms which are hard to culture (due to either innate difficulty of culturing, or pre-test use of antibiotics which inhibit growth).  Markers of immune status, either soluble cytokines or cell surface markers are also touted, although the stereotyped response to bacterial and sterile insults suggests to me that these will suffer from the same problems as existing laboratory measures of infection/inflammation.

It is a very controversial topic. Infectious complications of the central nervous system (e.g., meningitis, epidural abscess, or others) following regional anesthesia on febrile / septic patients . In 2006, a well written paper by Dr. Horlocker from Mayo Clinic summarized the conflicting results of the studies that examined neurological complications in septic patients undergoing regional anesthesia (Link). Recently and to my best knowledge, my research group have a developed the first meta-analysis of individual participant data (in Peer review yet) on this topic. A total of 234 meningitis cases were found following regional anesthesia, 199 of them were related to spinal anesthesia, of which only 2 cases had previous bacteremia / septicemia. However, it is important to say that in 110 of the 199 cases had not a clear cause of infection (not reported).

In conclusion, actually, there is not a general consensus. As for the actual clinical practice on this topic, sepsis or bacteremia is not still a contraindicated condition for spinal neither epidural anesthesia. 

Of course, it is advised to follow an aseptic technique during the procedure and, from my perspective, wearing surgical masks because the droplets may be a potential source of infection according to our recent work.

Hope this help to answer your interesting question.

Regards

Fabulous question. I thought one of the reasons we avoid administering pharmocological antipyretics was their anti-inflammatory effects not necessarily the effect of reducing core temperature. CVVHDF cools by convection so the effect of cooling is confined to the reduction in temperature rather than the effect on of reduced cytokine release on the inflammatory response. 

I will continue to follow this question with interest. 

PCT is a relatively specific marker of bacterial disease and may be produced by various organs including the thyroid, liver, testis, lung, prostate, kidney, and small intestine, but the secretion of PCT by a tumour has mainly been reported in small-cell

lung carcinoma and medullary thyroid carcinoma or neuroendocrine neoplasia.