New Guidelines Aim to Decrease Sepsis-Related Mortality
By Kelly M. Pyrek
Sepsis is an insidious complication, affecting more than 750,000 people annually and killing more than 1,400 in the U.S. daily. The Centers for Disease Control and Prevention (CDC) recently reported that septicemia has become the 10th leading cause of death. Knowing that there are more than 18 million cases of severe sepsis every year, leading critical-care specialists have formed a coalition to create greater awareness of sepsis and to encourage clinicians, physicians, and government and health agencies to adopt first-ever sepsis treatment guidelines.
The new guidelines were unveiled in February at the annual meeting of the Society of Critical Care Medicine (SCCM), and are designed to help bedside clinicians improve patient outcome in cases of severe sepsis and septic shock. The guidelines and the Surviving Sepsis Campaign are being co-administered by the SCCM, the European Society of Intensive Care Medicine (ESICM) and the International Sepsis Foundation (ISF). At a conference held to build consensus on the issue, the coalition agreed that swift, aggressive therapy administered in the initial hours after the syndrome develops will significantly impact clinical outcome.
The disease process is rather diffuse in how it involves the body, says R. Phillip Dellinger, MD, a member of the executive committee for the Surviving Sepsis Campaign and director of critical care at Cooper University Hospital in Camden, N.J. He likens the need for a quick diagnosis to that of a heart attack or aneurysm. Heart attacks and strokes are simpler and more straight-forward to deal with for clinicians. They understand the importance of moving quickly for these cases. We have clear signs to look for, such as abnormal EKGs and rising enzyme levels, so its easier to diagnose.
Dellinger adds, With sepsis, we are dealing with a disease that is not as easy to put your finger on, so it has not received the appropriate amount of attention. Its a tougher disease to tackle, but once we began working on the guidelines, we realized this was a doable project. We hope these tools are put into practice now against one of the most deadly enemies our profession faces every day.
The guidelines represent phase two of the campaign; phase one was initiated in October 2002 with an international declaration to improve survival in severe sepsis. The third phase will be dedicated to the use of the new sepsis-management guidelines to evaluate their impact on clinical outcomes.1 The key is adoption of these guidelines, as well as a greater early recognition of sepsis in the first place.
For many clinicians, I think sepsis is hard to diagnose early, Dellinger says. Once its beginning to create havoc, then its much easier to diagnose, obviously. There may be subtle presentations and manifestations of sepsis, such that you dont catch it as early as you should. Medical schools are not preparing residents (in the early recognition of sepsis), and even seasoned physicians arent certain about it sometimes. I would imagine medical students are inappropriately schooled in this area because I think they learn a lot about the patho-physiology of sepsis and how it can manifest in an organ system; as far as clinical correlates go, I think its more difficult to teach.
Clinicians have had prior instruction regarding sepsis in the form of 1992 guidelines that focused on diagnosis; its goals were to provide a conceptual and practical framework to define the systemic inflammatory response to infection, which is a progressive, injurious process that falls under the generalized term sepsis and includes sepsis-associated organ dysfunction as well. At a 2001 international conference, a group of experts revisited the 1992 sepsis guidelines and found that other than expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience, no evidence 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, explaining that the consortium looked at the medical literature to find any clinical trials having to do with any aspect of sepsis and septic shock treatment. The guidelines primarily are targeted toward earlier and more aggressive therapy, but in order to implement the guidelines you have to be able to identify the patients with severe sepsis and septic shock. The guidelines begin by identifying patients that have either infection and an elevated lactate, or infection and decreased blood pressure. Were looking at sepsis and organ hypo-profusion, the trigger point. Once you hit that trigger point, then the guidelines highlight early and aggressive implementation of treatment based on expert opinion and evidence-based literature.
The recommendations1 include:
- More aggressive recognition and diagnosis of sepsis in all hospital departments
- Monitoring of central venous oxygen-saturation levels
- Empiric, timely antibiotic therapy to fight the underlying infection
- Maintenance of adequate blood pressure through IV fluids and/or medications
- When localizable, removal or reduction of the source of the infection, such as a potentially infected catheter
Based on the most rigorous scientific evidence available, these recommendations standardize the approach toward clinical management of severe sepsis and are a major advance that will benefit hundreds of 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 upon evidencebased approaches. They include:
Resuscitation and Diagnosis
The guidelines say that resuscitation of a patient in severe sepsis or sepsis-induced tissue hypoperfusion (hypotension or lactic acidosis) should begin as soon as the syndrome is recognized and should not be delayed pending ICU admission. The rationale being that early goaldirected therapy has been shown to improve survival for ER patients presenting with septic shock in a randomized, controlled, single-center study.1 And when it comes to diagnosis, the recommendations say that appropriate cultures should always be obtained before antimicrobial therapy is initiated. To optimize identification of causative microorganisms, at least two blood cultures should be obtained, with at least one drawn percutaneously and one drawn through a vascular access device unless the device was inserted less than 48 hours previously. Experts say that if the same organism is recovered from both cultures, the likelihood that the organism is causing the severe sepsis is enhanced. Furthermore, the guidelines say that diagnostic studies should be performed promptly to determine the source of the infection and the causative organism. These diagnostic studies may identify a source of infection that must be drained to maximize the likelihood of a satisfactory response to therapy.
Antibiotic Therapy and Resistance Issues
The recommendations suggest that intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultures have been obtained. Experts say that establishing vascular access and initiating aggressive fluid resuscitation is the first priority when managing patients with severe sepsis or septic shock. Initial empirical anti-infective therapy should include one or more drugs that have activity against the likely pathogens and that penetrate into the presumed source of sepsis. The choice of drugs should be guided by the susceptibility patterns of microorganisms in the community and the hospital, and the antimicrobial regimen should be broad enough to cover all likely pathogens since there is little margin for error in critically ill patients.
The antimicrobial regimen should be reassessed after 48 to 72 hours on the basis of microbial and clinical data, with the aim of using a narrow- spectrum antibiotic to prevent the development of resistance, to reduce toxicity, and to reduce costs. Use of narrow-spectrum antibiotics will reduce the likelihood that the patient will develop superinfection with pathogenic or resistant organisms, experts say. They add that if the presenting clinical syndrome is determined to be due to a noninfectious cause, antimicrobial therapy should be stopped promptly to minimize the development of resistant pathogens.
We dont want clinicians to think about preventing antibiotic resistance when they initially choose their antibiotics, Dellinger says. When we initially choose antibiotics for patients with severe sepsis or septic shock, its important to address pathogens broadly and to consider resistance patterns in your hospital. After the patient has been appropriately initially treated with antibiotics, we emphasize re-evaluation at 48 to 72 hours to look at your culture results, decide whether or not this really was an infectious insult, and then to do everything you can to decrease the antibiotics you are going to continue with after that time period. Clinicians should think about preventing further resistance during that 48 to 72 hour reevaluation period when you can decrease the number of antibiotics given based on culture results or decide this really wasnt an infection driving this illness, and discontinue antibiotics altogether. Thats where you can achieve cost savings and prevent resistance.
Controlling the Source
The recommendations emphasize controlling the source of infection. Every patient presenting with severe sepsis should be evaluated for the presence of a focus on infection amenable to source-control measures. The guidelines dictate that healthcare professionals should obtain diagnostic samples and to drain, debride or remove the infection source as appropriate. Experts recommend that if intravascular access devices are potentially the source of severe sepsis or septic shock, they should be promptly removed after establishing other vascular access because these devices are thought to be the source of the majority of nosocomial bloodstream infections.
Being pro-active and not merely reactive is essential when treating sepsis, and Dellinger takes a pragmatic view of what the new sepsis guidelines can and cannot achieve.
Guidelines can fail ... they may save a patient here or there but I dont think you can ever measure clinical outcome improvement with guidelines, he says. The key is actively doing something with them.
We worked with the Institute of Healthcare Improvement, a world leader in provoking change in healthcare-practitioner behavior. The institute has been very successful at engendering change within hospitals in a positive fashion. They do it by recognizing that you cant simply give people 45 recommendations and say, We believe these will improve outcome in your patients with severe sepsis or septic shock, here they are, go to it. It never works.
Dellinger continues, We have worked with the institute to create something called sepsis bundles, where facilities identify key elements of the sepsis guidelines and determine which elements that, if people were to follow them, would stand a good chance of decreasing sepsisrelated mortality. Its important to select recommendations currently not being followed that you know are feasible to implement. The key to success in using these bundles is to ensure the elements you choose to pursue are important to clinical outcomes, that they are do-able, and that they are measurable. Lets admit you cant ask people to do 45 things; instead, lets identify seven or eight things you could ask them to do that are measurable and able to be analyzed. Thats how you create bundles.
Dellinger says experts have created a four-hour bundle and a 24- hour bundle in which specific goals are identified. Every goal has a failure mode that can be measured. So, for example, the goal is to give antibiotics within one hour after the diagnosis of severe sepsis or septic shock. By using retrospective chart review, you can measure whether thats being done or not, and you also get a baseline. You tell staff what their baseline performance is, and through a facilitys educational program, you educate them and then finally you give people periodic feedback. Its crucial to give performance evaluations and feedback in order to motivate people toward reaching their goal.
Dellinger says the sepsis bundles first were deployed in late March in hospitals working with the Institute of Healthcare Improvement. We should have data from them in the next few months, he adds. We intend to put the sepsis bundles in other hospital systems, too.
Therapies for Sepsis
A number of therapies are used to treat severe sepsis and septic shock, including antibiotic therapy and fluid resuscitation that includes colloids or crystalloids, but when these approaches fail, the new sepsis guidelines recommend therapy with vasopressor agents to restore blood pressure and organ perfusion. Either norepinephrine or dopamine is the first-choice vasopressor agent to correct hypotension, and all patients requiring vasopressors should have an arterial catheter placed as soon as practical if resources are available. Regarding inotropic therapy, the guidelines recommend that for patients with low cardiac output despite adequate fluid resuscitation, dobutamine may be used to increase cardiac output. If used in the presence of low blood pressure, it should be combined with vasopressor therapy. Intravenous corticosteroids are recommended in patients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain adequate blood pressure. Additionally, the recommendations say Recombinant Human Activated Protein C (rhAPC) is advisable for patients at high risk of death and with no absolute contraindication related to bleeding risk or relative contraindication that outweighs the potential benefit of rhAPC.
I am very encouraged with early goal-directed therapy, the steroids and with the activated protein C, Dellinger says. I think all of them are therapies that need to be matched with the appropriate patients. When properly matched, I believe we now have, for the first time, therapies that we know for certain can make a difference.
The Surviving Sepsis Campaigns goal is to reduce the number of sepsis- related deaths by 25 percent in five years, and Dellinger says its a plausible, attainable goal. Eleven professional medical societies gave the new sepsis guidelines their stamp of approval, but so far, Dellinger says, no other healthcare-related agencies, such as the CDC, have picked up the cause.
Thats a shame, but we are discussing potential implementation of the sepsis bundles through various state health systems. We remain hopeful our message will be heard.