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By Kelly M. Pyrek
Sepsis is an insidious complication,affecting more than 750,000 people annually and killing more than 1,400 in theU.S. daily. The Centers for Disease Control and Prevention (CDC) recentlyreported that septicemia has become the 10th leading cause of death. Knowingthat there are more than 18 million cases of severe sepsis every year, leadingcritical-care specialists have formed a coalition to create greater awareness ofsepsis and to encourage clinicians, physicians, and government and healthagencies to adopt first-ever sepsis treatment guidelines.
The new guidelines were unveiled in February at the annualmeeting of the Society of Critical Care Medicine (SCCM), and are designed tohelp bedside clinicians improve patient outcome in cases of severe sepsis andseptic shock. The guidelines and the Surviving Sepsis Campaign are beingco-administered by the SCCM, the European Society of Intensive Care Medicine(ESICM) and the International Sepsis Foundation (ISF). At a conference held tobuild consensus on the issue, the coalition agreed that swift, aggressivetherapy administered in the initial hours after the syndrome develops willsignificantly impact clinical outcome.
The disease process is rather diffuse in how it involvesthe body, says R. Phillip Dellinger, MD, a member of the executivecommittee for the Surviving Sepsis Campaign and director of critical care atCooper University Hospital in Camden, N.J. He likens the need for a quickdiagnosis to that of a heart attack or aneurysm. Heart attacks and strokesare simpler and more straight-forward to deal with for clinicians. Theyunderstand the importance of moving quickly for these cases. We have clear signsto look for, such as abnormal EKGs and rising enzyme levels, so its easier todiagnose.
Dellinger adds, With sepsis, we are dealing with a diseasethat is not as easy to put your finger on, so it has not received theappropriate amount of attention. Its a tougher disease to tackle, but once webegan working on the guidelines, we realized this was a doable project. We hope these tools are put into practice now against one ofthe most deadly enemies our profession faces every day.
The guidelines represent phase two of the campaign; phase onewas initiated in October 2002 with an international declaration to improvesurvival in severe sepsis. The third phase will be dedicated to the use of thenew sepsis-management guidelines to evaluate their impact on clinical outcomes.1The key is adoption of these guidelines, as well as a greater early recognitionof sepsis in the first place.
For many clinicians, I think sepsis is hard to diagnose early, Dellinger says. Once its beginning to create havoc, thenits much easier to diagnose, obviously. There may be subtle presentations andmanifestations of sepsis, such that you dont catch it as early as you should. Medical schools are not preparing residents (in the earlyrecognition of sepsis), and even seasoned physicians arent certain about itsometimes. I would imagine medical students are inappropriately schooledin this area because I think they learn a lot about the patho-physiology ofsepsis and how it can manifest in an organ system; as far as clinical correlatesgo, I think its more difficult to teach.
Clinicians have had prior instruction regarding sepsis in theform of 1992 guidelines that focused on diagnosis; its goals were to providea conceptual and practical framework to define the systemic inflammatoryresponse to infection, which is a progressive, injurious process that fallsunder the generalized term sepsis and includes sepsis-associated organdysfunction as well. At a 2001 international conference, a group of expertsrevisited the 1992 sepsis guidelines and found that other than expanding thelist of signs and symptoms of sepsis to reflect clinical bedside experience, noevidence existed to support a change to the earlier definitions.2
This is the first large-scale effort to get specific,graded management recommendations to clinicians, Dellinger says, explainingthat the consortium looked at the medical literature to find any clinical trialshaving to do with any aspect of sepsis and septic shock treatment. Theguidelines primarily are targeted toward earlier and more aggressive therapy,but in order to implement the guidelines you have to be able to identify thepatients with severe sepsis and septic shock. The guidelines begin byidentifying patients that have either infection and an elevated lactate, orinfection and decreased blood pressure. Were looking at sepsis and organhypo-profusion, the trigger point. Once you hit that trigger point, then theguidelines highlight early and aggressive implementation of treatment based onexpert opinion and evidence-based literature.
The recommendations1 include:
Based on the most rigorous scientific evidenceavailable, these recommendations standardize the approach toward clinicalmanagement of severe sepsis and are a major advance that will benefit hundredsof thousands of sepsis patients in the years ahead, says Graham Ramsay, MD,of the University Hospital Maastricht in the Netherlands, and president of the ESICM. The guidelines make a number of specific points built uponevidencebased approaches. They include:
Resuscitation and Diagnosis
The guidelines say that resuscitation of a patient in severesepsis or sepsis-induced tissue hypoperfusion (hypotension or lactic acidosis)should begin as soon as the syndrome is recognized and should not be delayedpending ICU admission. The rationale being that early goaldirected therapy hasbeen shown to improve survival for ER patients presenting with septic shock in arandomized, controlled, single-center study.1 And when it comes to diagnosis,the recommendations say that appropriate cultures should always be obtainedbefore antimicrobial therapy is initiated. To optimize identification ofcausative microorganisms, at least two blood cultures should be obtained, withat least one drawn percutaneously and one drawn through a vascular access deviceunless the device was inserted less than 48 hours previously. Experts say thatif the same organism is recovered from both cultures, the likelihood that theorganism is causing the severe sepsis is enhanced. Furthermore, the guidelines say that diagnostic studies shouldbe performed promptly to determine the source of the infection and the causativeorganism. These diagnostic studies may identify a source of infection that mustbe drained to maximize the likelihood of a satisfactory response to therapy.
Antibiotic Therapy and Resistance Issues
The recommendations suggest that intravenous antibiotictherapy should be started within the first hour of recognition of severe sepsis,after appropriate cultures have been obtained. Experts say that establishingvascular access and initiating aggressive fluid resuscitation is the firstpriority when managing patients with severe sepsis or septic shock. Initial empirical anti-infective therapy should include one ormore drugs that have activity against the likely pathogens and that penetrateinto the presumed source of sepsis. The choice of drugs should be guided by thesusceptibility patterns of microorganisms in the community and the hospital, andthe antimicrobial regimen should be broad enough to cover all likely pathogenssince there is little margin for error in critically ill patients.
The antimicrobial regimen should be reassessed after 48 to 72hours on the basis of microbial and clinical data, with the aim of using anarrow- spectrum antibiotic to prevent the development of resistance, to reducetoxicity, and to reduce costs. Use of narrow-spectrum antibiotics will reducethe likelihood that the patient will develop superinfection with pathogenic orresistant organisms, experts say. They add that if the presenting clinicalsyndrome is determined to be due to a noninfectious cause, antimicrobial therapyshould be stopped promptly to minimize the development of resistant pathogens.
We dont want clinicians to think about preventingantibiotic resistance when they initially choose their antibiotics, Dellingersays. When we initially choose antibiotics for patients with severe sepsis orseptic shock, its important to address pathogens broadly and to considerresistance patterns in your hospital. After the patient has been appropriatelyinitially treated with antibiotics, we emphasize re-evaluation at 48 to 72 hoursto look at your culture results, decide whether or not this really was aninfectious insult, and then to do everything you can to decrease the antibioticsyou are going to continue with after that time period. Clinicians should think about preventing further resistanceduring that 48 to 72 hour reevaluation period when you can decrease the numberof antibiotics given based on culture results or decide this really wasnt aninfection driving this illness, and discontinue antibiotics altogether. Thats where you can achieve cost savings and preventresistance.
Controlling the Source
The recommendations emphasize controlling the source ofinfection. Every patient presenting with severe sepsis should beevaluated for the presence of a focus on infection amenable to source-controlmeasures. The guidelines dictate that healthcare professionals shouldobtain diagnostic samples and to drain, debride or remove the infection sourceas appropriate. Experts recommend that if intravascular access devices arepotentially the source of severe sepsis or septic shock, they should be promptlyremoved after establishing other vascular access because these devices arethought to be the source of the majority of nosocomial bloodstream infections.
Being pro-active and not merely reactive is essential whentreating sepsis, and Dellinger takes a pragmatic view of what the new sepsisguidelines can and cannot achieve.
Guidelines can fail ... they may save a patient here orthere but I dont think you can ever measure clinical outcome improvement withguidelines, he says. The key is actively doing something with them.
We worked with the Institute of Healthcare Improvement, aworld leader in provoking change in healthcare-practitioner behavior. Theinstitute has been very successful at engendering change within hospitals in apositive fashion. They do it by recognizing that you cant simply give people45 recommendations and say, We believe these will improve outcome in yourpatients with severe sepsis or septic shock, here they are, go to it. Itnever works.
Dellinger continues, We have worked with the institute tocreate something called sepsis bundles, where facilities identify key elementsof the sepsis guidelines and determine which elements that, if people were tofollow them, would stand a good chance of decreasing sepsisrelated mortality. Itsimportant to select recommendations currently not being followed that you knoware feasible to implement. The key to success in using these bundles is toensure the elements you choose to pursue are important to clinical outcomes,that they are do-able, and that they are measurable. Lets admit you cantask people to do 45 things; instead, lets identify seven or eight things youcould ask them to do that are measurable and able to be analyzed. Thats howyou create bundles.
Dellinger says experts have created a four-hour bundle and a24- hour bundle in which specific goals are identified. Every goal has afailure mode that can be measured. So, for example, the goal is to giveantibiotics within one hour after the diagnosis of severe sepsis or septicshock. By using retrospective chart review, you can measure whether thatsbeing done or not, and you also get a baseline. You tell staff what theirbaseline performance is, and through a facilitys educational program, youeducate them and then finally you give people periodic feedback. Its crucial to give performance evaluations and feedback inorder to motivate people toward reaching their goal.
Dellinger says the sepsis bundles first were deployed in lateMarch in hospitals working with the Institute of Healthcare Improvement. Weshould have data from them in the next few months, he adds. We intend toput the sepsis bundles in other hospital systems, too.
Therapies for Sepsis
A number of therapies are used to treat severe sepsis andseptic shock, including antibiotic therapy and fluid resuscitation that includescolloids or crystalloids, but when these approaches fail, the new sepsisguidelines recommend therapy with vasopressor agents to restore blood pressureand organ perfusion. Either norepinephrine or dopamine is the first-choicevasopressor agent to correct hypotension, and all patients requiringvasopressors should have an arterial catheter placed as soon as practical ifresources are available. Regarding inotropic therapy, the guidelines recommendthat for patients with low cardiac output despite adequate fluid resuscitation,dobutamine may be used to increase cardiac output. If used in the presence oflow blood pressure, it should be combined with vasopressor therapy. Intravenouscorticosteroids are recommended in patients with septic shock who, despiteadequate fluid replacement, require vasopressor therapy to maintain adequateblood pressure. Additionally, the recommendations say Recombinant HumanActivated Protein C (rhAPC) is advisable for patients at high risk of death andwith no absolute contraindication related to bleeding risk or relativecontraindication that outweighs the potential benefit of rhAPC.
I am very encouraged with early goal-directed therapy, thesteroids and with the activated protein C, Dellinger says. I think all ofthem are therapies that need to be matched with the appropriate patients. When properly matched, I believe we now have, for the firsttime, therapies that we know for certain can make a difference.
The Surviving Sepsis Campaigns goal is to reduce the numberof sepsis- related deaths by 25 percent in five years, and Dellinger says itsa plausible, attainable goal. Eleven professional medical societies gave the newsepsis guidelines their stamp of approval, but so far, Dellinger says, no otherhealthcare-related agencies, such as the CDC, have picked up the cause.
Thats a shame, but we are discussing potentialimplementation of the sepsis bundles through various state health systems. Weremain hopeful our message will be heard.