Sepsis is a serious and often deadly illness, yet it remains an unfamiliar threat to most of the general public, as well as one of the most difficult diseases for doctors to diagnose and treat. The condition, which begins with an aggressive immune system reaction to an infection, kills 18 million people around the world every year, including around 260,000 in the U.S. By many estimates, sepsis—and its most severe form, septic shock—is the leading cause of death for intensive care patients in the U.S. and the 10th most common cause of death for everyone else in the country. Yet only one in five Americans recognizes the term, according to a 2011 study commissioned by the nonprofit group Sepsis Alliance, and of those survey participants who had heard of sepsis, most could not define it.

Even physicians, who learn about sepsis in medical school, often miss its early signs because they mimic other disorders and because the illness progresses so rapidly from what looks like a mild infection to a life-threatening situation. As a result of these difficulties, doctors are often late to launch the necessary interventions, such as antibiotics to obliterate the infection, drugs to counteract a perilous drop in blood pressure, and a mechanical ventilator to raise dangerously low oxygen levels.

“The timing of antibiotics is a critical determinant for whether someone lives or dies,” says James O'Brien, who is medical director of quality and patient safety at Riverside Methodist Hospital in Columbus, Ohio, and serves as an adviser to Sepsis Alliance. But some of the most compelling data out there, he says, shows that only 50 percent of patients with septic shock get appropriate antibiotics within six hours of first being seen by a health professional. “If we had a similar record with getting heart attack patients to the catheterization lab, there would be an uproar,” he adds.

To further complicate the picture, better treatments have been slow in coming. Some are on the horizon—such as an experimental blood test and filtration therapy—but failure of four potential antisepsis drugs in the past two years has discouraged researchers and advocates alike. Carl Flatley, a retired dentist, founded Sepsis Alliance after his daughter died of the syndrome in 2002. “In the 10 years since, we have lost 2.5 million people to this [in the U.S.], and it could take another 10 years before we have something that works,” he says. “We need to move faster.”

Chemical Cascade

Sepsis begins innocuously enough when the immune system performs its usual task of recognizing invading bacteria, viruses or fungi. Immune cells release signaling proteins called cytokines to stimulate one another and overcome the invaders—but for poorly understood reasons, the immune cells release far more cytokines and other inflammatory molecules than is typical. All the extra immune molecules surging through the bloodstream have the inadvertent effect of making blood vessels slack and permeable, reducing blood pressure and allowing the fluid component of the blood to seep into surrounding tissues. The blood components left behind clot in the smallest vessels, preventing oxygen from reaching major organs. At this point, someone with sepsis has transitioned from the earliest stage of the disease, known as systemic inflammatory response syndrome, to the later stages of severe sepsis and septic shock. Confusion sets in, the heart's electrical activity becomes erratic, the kidneys and other organs fail, and blood pressure cannot be raised even with large amounts of intravenous fluids and drugs.

Because the immune system's reaction is responsible for the destructive progression of sepsis, researchers have tried using various drugs to interrupt the chemical cascade that triggers inflammation and clotting. Recent attempts have been disappointing.

11 Comments

1. 1. Guest1976 09:51 AM 3/27/13

   Hi Maryn,
   
   thanks for this very nice and informative article.
   
   You are mentioning "an experimental blood test and filtration therapy" as a treatment on the horizon. Are you referring to Cytosorb here, the flagship product of Cytosorbents? According to their website, this Monmouth Junction, NJ based company has an extracorporeal cytokine filter approved in the European Union. The Cytosorb filter has achieved European regulatory approval (CE Mark) in 2011 and is now available for sale and clinical use in Europe.
   
   If I'm not mistaken they are actually using this device in German hospitals as we speak. What's your opinion on their approach?

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2. 2. ironjustice 04:20 PM 3/27/13

   There is a very good chance the addition of the metal iron to all our foods has caused an increase of iron stores in the population which has now risen to such a point the body is unable to mount an efficient immune response because there is just too much iron to contend with ?
   "It has been determined that the infection incidence is significantly higher in dialysed patients with a serum iron level higher than 500 g/L, than in those patients
   with lower values."
   "When iron is given during experimental sepsis
   approximately 60% mortality, result"

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3. 3. noretreat 04:45 PM 3/27/13

   Cytosorbent's filter for the "cytokine storm" has been approved in europe for some time. THere doesn't seem to be much movement toward USA approval, for reasons that are a mystery to me.
   
   Another company putting hope on the horizon is Trius Theraputics, which recently toplined a phase 3 study of Tedizolid. Tedizolid is a very promising "next" treatment for resistant infections.

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4. 4. voice 08:38 AM 3/28/13

   Thank you for this clear and informative article. Doctors need to be educated on this subject, at least in my city. Following surgery and with a temperature of 96F and white count well above normal range, my (previous) primary care physician and the surgeon (a GYN) refused to treat me for infection, although I had a documented history of strep following surgery. As a result my career and my health were destroyed. As a result of my experience,I have come to suspect that the war on antibiotics is responsible for the rise in autoimmune illness. Given that doctors can simply choose to withhold antibiotics, it is important for us to educate ourself about alternatives such as nicotine for sepsis and silver for infection. The medical establishment has no interest in a $4 shot of penicillin. A $25,000 steroid infusion for MS is more up their alley.

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5. 5. ironjustice 11:13 AM 3/28/13

   The lack of the proper fatty acids in the body it thought to contribute to the problem of sepsis.
   “Lecithin therapy may be a useful adjuvant therapy in patients with severe sepsis.”
   
   The same problem which happens when one is struck with meningitis.
   "Supplementation with lyso-phosphatidylcholine prevents cell death"
   
   

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6. 6. ironjustice 04:21 PM 3/29/13

   As mentioned , iron accumulation is thought to prevent the body from being able to mount an efficient enough defense and a substance the green tea component, EGCG,
   which coincidentally chelates iron , seems to show some efficacy.
   "Green Tea Proves Powerful Medicine Against Sepsis"
   
   "EGCG exhibited potent iron-chelating activity comparable to that of the prototype iron chelator desferrioxamine"

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7. 7. lamclaurin 08:12 PM 4/1/13

   There are hundreds of Pubmed articles on the use of high dose intravenous vitamin C on sepsis. It has been used in the past; but mostly at sub-theraputic dosing; and is starting to have a resurgence. The Riordan Clinic is a leader in some of the recent research. IVC is necessary for all hormone function, it decreases the inflammatory response through supression of the cytokine response. It is also responsible for improving the function of the and creation of WBC's. It is also a chelating agent, so the concerns that the "ironman" above has can be resolved. It is all dose dependent, so escalation of dosing is every 4 hours until symptoms are stayed and then reversed. This may involve dosing from 10,000mg up to 500,000mg over a 24/hr period. There is also no development of resistance as there is to antibiotics. There are many, many more things IVC does and is something we need to see more mainstream again!

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8. 8. bucketofsquid 06:09 PM 4/4/13

   It is nice that someone recognizes that we are not all clones of a single person. What works for one person may kill another. Something the health food and "nutritional supplement" industry seems completely ignorant of. I love soy beans but 2 of my friends suffered thyroid collapse immediately after eating food with soy in it.
   
   Would it not be better to focus on early detection of sepsis and find a low cost, easy to use method? If you treat before septic-shock it would be less deadly and probably cheaper due to the lack of malpractice law suits.

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9. 9. arnoldhuang 09:18 AM 4/18/13

   Maryn McKenna’s article, “Researchers Struggle to Develop New Treatments for Sepsis,” highlights many of the challenges in finding new and effective treatments for this often deadly disease. While better therapeutics are needed, equally important is having diagnostic tools, including biomarkers that can improve early detection of sepsis. Earlier identification leads to earlier intervention, which is crucial to reducing sepsis morbidity and mortality.
   
   Approaches to sepsis identification and risk assessment using various biomarkers are already in use. In particular, the protein procalcitonin has been shown to have elevated levels in response to microbial infections and to be sensitive in the early identification of sepsis. Procalcitonin has been studied extensively with more than 2,000 published articles in peer-reviewed journals and is useful as a biomarker for sepsis risk assessment. Greater focus and continued research on such biomarkers will further aid in identifying and treating this deadly condition and improving patient outcomes.
   
   Arnold Huang, Ph.D.
   Thermo Fisher Scientific
   Middletown, VA
   http://www.thermofisher.com/global/en/aboutsepsis/home.asp
   

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10. 10. DorothyLanasa 01:05 PM 4/19/13

    I WAS HIT ON IN A RESTAURANT AND GOT A TERRIBLE CASE OF SEPSIS (CHINESE RESTAURANT IN BALTIMORE). I WAS SICK TWO OR THREE YEARS, VERY TIRED, ETC. A VERY TALENTED DOCTOR OF PSYCHIATRY GOT ME WELL. I WAS GIVEN PAXEL AND ABILIFY FOR A YEAR OR MORE, AND THEN PAXEL AND GEODON. I EAT VERY WELL; MY DIET IS MOSTLY FRUITS AND VEGGIES, WHOLE GRAINS AND SEAFOOD/MEAT/POULTRY IN REASONABLE QUANTITIES. (I ALSO WONDER ABOUT MARROW BONE SOUP -DOES THIS HEAL HUMAN MARROW?)

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11. 11. lamclaurin in reply to arnoldhuang 07:44 PM 4/21/13

    As a bedside nurse, I can tell you that early recognition doesn't happen because of individual physicians choice on how to treat sirs/sepsis before they go into shock. Procalcitonin is a gread indicator of when to get rid of the antibiotics, but the key to treating sepsis lies in treating the persons who don't have hypotension yet, with the current modalities of IV fluids and antibiotics; 250ml or 500ml of fluid doesn't count as aggressive treatment. 30% or more of this untreated group later dies. The use of IVC can inhibit at least 22 cytokine repsonses, therefore halting and reversing sepsis/ARDS. It also would quickly drop the procalcitonon levels and help decrease antibiotic use. A way to help current with the current methods is to have ways to flag patients who meet criteria as it happens; HR>90, RR>20, T<35*>38*, serial Lactate levels >2-4 and notification of the doctor ASAP so the IVF and antibiotics can be given within the first hour. Very few institutions have anything solidly put in place. We have a long ways to go with recognition and rapid treatment....I'm very excited though that there are people here expressing their concern also :)

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