Critical Care Nurse. 2006;26: 43-54
Copyright © 2006 by the American Association of Critical-Care Nurses.
Clinical Article
CE Online
Development and Implementation of a Multidisciplinary Sepsis Protocol
Kathy M. Picard, RN, MS, CCRN
Sharon C. O’Donoghue, RN, MS
Duane A. Young-Kershaw, RN, BSN
Kristin J. Russell, RN, BSN
Kathy Picard is the clinical nurse specialist, Sharon O’Donoghue is a clinical nurse educator, and Kristin Russell is a nurse manager in the medical intensive care units and Duane Young-Kershaw is the clinical nurse educator in the emergency department at Beth Israel Deaconess Medical Center, Boston, Mass.
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Sepsis is a complex condition that is often life threatening. It is characterized by hematological derangements and a profound inflammatory response to an infection or injury. Despite recent advances in critical care, sepsis affects more than 750000 patients and accounts for 215000 deaths in the United States each year, at a cost of more than $16 billion.1 Mortality in septic shock has decreased only slightly between 1970 and the late 1990s; it remains the most frequent cause of death in noncardiac intensive care units (ICUs). Septicemia is currently ranked by the Centers for Disease Control and Prevention as the 10th leading cause of death in the United States.2(p27) Incredibly, and perhaps more disturbing, severe sepsis is responsible for the deaths of more Americans than are colon, breast, prostate, and pancreatic cancers combined, and the mortality rate for sepsis is virtually equal to the rate for acute myocardial infarction (Figure 1
).
Sepsis consists of a series of inflammatory and hemostatic alterations presumably caused by invasion of the bloodstream by micro organisms. However, a subset of critically ill patients have features characteristic of sepsis despite blood cultures that are repeatedly negative for microorganisms and no identified source of bacterial, fungal, or viral infection.5 Trauma, surgery, burns, and illnesses such as cancer and pneumonia can trigger the onset of sepsis. In 1991, the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference6 outlined definitions for systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (Table 1). These definitions have been widely adopted. They have allowed greater consistency in diagnosis and treatment and in tracking statistics on the incidence and occurrence of sepsis.
Patients vulnerable to sepsis may have a number of risk factors7,8 (Table 2). Despite the wide variety of patients who initially have systemic inflammatory response syndrome, if the syndrome is not self-limiting and progresses to sepsis, the disease progression is fairly homogeneous. Cellular mediators are produced early in the onset of sepsis and initiate a cascade of events, including activation of the coagulation and complement pathways, vasodilation leading to hypotension, endothelial dysfunction and fluid transudation, and generalized inflammation. A triad of events occurs, consisting of a profound inflammatory response, processes that promote coagulation, and impaired fibrinolysis. In healthy persons, homeostasis is maintained because these 3 mechanisms balance one another (see Sidebar 1).
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Background of the Protocol
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Treatment of sepsis is largely focused on supporting failing organ systems. Interventions include fluid replacement, airway management, antibiotic therapy, use of vasoactive medications, and hemodialysis. Various treatments used to improve patients’ outcomes can paradoxically contribute to organ dysfunction. Examples of these treatments include the use of high-tidal-volume ventilation to improve oxygenation, which may cause barotrauma or damage of the lung parenchyma; use of antimicrobial agents that cause nephrotoxic effects; and hemodialysis in renal dysfunction, which may worsen a preexisting coagulopathy.
Recent studies have shown that early goal-directed therapy is beneficial to patients with sepsis.10 Advances in the management of severe sepsis and septic shock have resulted in improved survival for these critically ill patients. Current management includes early goal-directed therapy,10 activated protein C for severe sepsis,11 intensive insulin therapy,12 steroids for patients with adrenal suppression,13 and protective lung ventilation.14 Rivers et al10 reported the use of early goal-directed therapy in patients entering the emergency department with sepsis or septic shock. The therapy, which included manipulating preload by using fluids and blood transfusions and manipulating oxygen delivery by using vasopressors, inotropic agents, and blood transfusions, resulted a significant improvement in mortality. Mortality rates were 46.5% in the control group and 30.5% in the treatment group, for an absolute reduction in death of 16%.
At Beth Israel Deaconess Medical Center (BIDMC) in Boston, Mass, caregivers identified an opportunity to improve patients’ care by initiating an aggressive treatment protocol early in the hospital course of patients who have sepsis. The BIDMC protocol incorporates early goal-directed therapy based on the study by Rivers et al10 and includes use of antibiotics early on, activated protein C, steroids, insulin therapy, and protective lung ventilation. This comprehensive protocol was titled the Multiple Urgent Sepsis Therapies (MUST) Protocol. We chose MUST as a title for our protocol because the argument that these therapies must be delivered to patients with sepsis is compelling and because the approach incorporates several different therapies. A description of each of the therapies is provided in Sidebar 2. Table 3 summarizes nursing actions and expected outcomes for each of these therapies. Supportive therapy also includes proper handwashing, enforcing infection control measures, use of semirecumbent positioning during mechanical ventilation, stress ulcer prophylaxis, prevention of deep vein thrombosis, turning, and skin care.5,7 A complete summary of the MUST Protocol can be viewed online at www.mustprotocol.org.
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BIDMC Protocol
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Members of the BIDMC emergency department and surgical and medical ICUs formed a multidisciplinary team made up of physicians and nurses to design ways to implement this quality improvement pathway. The purpose of the protocol is early recognition of sepsis and treatment of patients with sepsis with proven therapies. The team’s goals were to develop a multidisciplinary, evidence-based protocol that would allow for rapid identification and early triage of patients and to educate and empower nurses to use the protocol to manage patients with sepsis.
Physician and nursing leaders from the BIDMC emergency department and ICUs convened a series of bimonthly meetings to develop the content of the protocol, to identify team members, and to determine the resources required to develop and implement the protocol. A literature review was completed, and a time line was established. Key clinical nurses representing the ICUs, emergency department, and admission facilitation (nursing capacity managers) were asked to join the team to assist with planning and implementation. The goals were to have representation and acceptance of the protocol by members from all disciplines and staff who would be involved in use of the protocol and to have input from these team members about how the protocol would affect all areas of practice. Meeting attendance was mandatory; members who were unable to attend appointed a proxy. Communication among members was necessary to ensure collaboration and to coordinate activities. Each member was held accountable for the information to keep the project on track. Minutes were drafted for each meeting and were distributed via e-mail.
Eligibility of Patients
Patients were eligible for the protocol if they were 18 years or older and had signs and symptoms suggestive of infection, met 2 or more criteria for systemic inflammatory response syndrome, and had evidence of hypoperfusion (Table 4). Hypoperfusion was defined as systolic blood pressure less than 90 mm Hg after a administration of a bolus of fluid of 20 to 30 mL/kg and/or a serum lactate level greater than 4 mmol/L. Suspected infections included pneumonia, meningitis, intra-abdominal infection, urinary tract infection, and catheter infections; a fever (body temperature >38.0°C [>100.4°F]) was considered a sign of a suspected infection.
To practically implement the lactate screening, emergency department nurses initiated a standing policy that they would obtain measurements of serum lactate in all patients who had blood samples obtained for cultures or who had signs and symptoms suggestive of infection. Samples of venous blood were used for assays of lactate because these samples are easily obtained and the results are roughly equivalent to those of assays of arterial samples.24 Thus, the serum level of lactate was used as a screening tool. Lactate was chosen because it is used as a prognostic marker of global tissue hypoxia and because the clearance of circulating lactate is prolonged in patients with sepsis. Our group has recently published data25 indicating that patients with a suspected infection had a higher hospital mortality rate when their venous serum level of lactate was elevated at the time of admission to the emergency department. The 28-day in-hospital mortality rate for patients with a venous serum lactate level of 4 mmol/L or greater was 28% (38 deaths of 134 patients), versus a mortality rate of 5.9% (67 deaths of 1144 patients) for patients with a venous lactate level less than 4 mmol/L (Figure 2). We endorse the measurement of serum lactate as a promising and effective screening tool because the assay is relatively easy to obtain, is inexpensive, and has a rapid laboratory turnaround time.
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Figure 2 Serum lactate level as a predictor of mortality in patients with sepsis (n = 1278). The 28-day in-hospital mortality was 8.2% (105 patients); death occurred within 3 days in 4.3% (55 patients).
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The Sepsis Team
Patients are triaged and the BIDMC protocol is initiated in the emergency department. Emergency department nurses assess patients by using the previously described criteria and activate a "code sepsis." Once nurses determine that a patient meets the eligibility criteria for the protocol, members of the sepsis pathway team are paged. The team includes, but is not limited to, the ICU attending physician and resident, emergency department attending physician and resident, the ICU clinical nurse specialist, and the nursing admission facilitator. The rationale is that by alerting the right clinicians quickly, we can mobilize an early resuscitation effort and prepare the ICU to assume care of the patient.
Entry Documentation
An intake and tracking form (Figure 3) for patients with sepsis was designed by the team to guide nurses in implementing the MUST protocol. This form was modeled on the current emergency department trauma flow sheet so that nurses would be familiar with most of its content and layout. The vision of the group was that the protocol would be used by nurses and that the intake and tracking form would guide nurses at the bedside in a checklist fashion. All interventions, collections of blood samples, and treatments are included on the form so that no part of the pathway is missed.
Components of the MUST Protocol
Early goal-directed therapy, as described by Rivers et al,10 is the heart of the resuscitation interventions in the MUST protocol (Figure 4). All patients receive supplemental oxygen or mechanical ventilation as needed to maintain adequate oxygenation and ventilation. A central venous catheter is placed in the emergency department to monitor the need for fluid replacement. The goal is a central venous pressure (CVP) of 8 to 12 mm Hg.10 If the CVP is less than 8 mm Hg, 500 mL of isotonic sodium chloride solution is given. Lung sounds are evaluated for tolerance of the fluid bolus and, if the lung sounds are stable, the bolus is repeated every 20 to 30 minutes until the CVP reaches 8 mm Hg. The target mean arterial pressure (MAP) is 65 to 90 mm Hg.10 If MAP remains low after the CVP is greater than 8 mm Hg, vasopressor therapy, preferentially with norepinephrine, is started. Studies have shown that the use of norepinephrine can improve outcomes in patients with septic shock.17 Fluid replacement and vasopressor therapy are managed by the nurse caring for the patient. The nurse has the protocol as ordered by the physician; this arrangement enables the nurse to monitor and assess the patient’s response to the protocol interventions and quickly respond without the need to obtain further orders from the physician.
At BIDMC, a catheter (PreSep Catheter, Edwards Lifesciences, Irvine, Calif ) that measures CVP as well as central venous oxygen saturation (ScvO2) is inserted to evaluate end-organ perfusion. Mixed venous oxyhemoglobin levels provide an indication of the balance between oxygen delivery and consumption. Normal tissue oxygen extraction is approximately 25%; therefore normal ScvO2 is 70% to 80%. With the early goal-directed therapy protocol, after the CVP and MAP have been normalized, the ScvO2 is assessed. If the ScvO2 is less than 70% and the hematocrit is less than 0.30, a blood transfusion is given to improve oxygen delivery to the tissues. If, after the blood transfusion, the hematocrit is greater than 0.30 and the ScvO2 remains less than 70%, dobutamine is given as a continuous infusion to increase cardiac output.
Because the main objective of the MUST Protocol is to decrease the time between identification of patients with sepsis and the start of interventions, the team set a target time limit of 5 hours from a patient’s enrollment in the protocol to placement in an ICU bed. Once the patient is transferred to the ICU, treatments and interventions continue according to the protocol. Broad-spectrum antimicrobial therapy is started as soon as possible in the emergency department and is directed at the suspected cause of infection. A random blood sample for determination of serum cortisol level is obtained, and then a corticotropin stimulation test is done. Patients who do not have an increase in cortisol greater than 248 nmol/L (>9 µg/dL) receive steroid replacement for 7 days.
Glucose levels are monitored at least every 6 hours. Insulin therapy is initiated to maintain blood glucose levels between 4.4 and 6.7 mmol/L (80–120 mg/dL). The Acute Respiratory Distress Syndrome Network 2000 guidelines14 are used to manage patients with acute lung injury or acute respiratory distress syndrome; low-tidal-volume ventilation is used to decrease airway pressures. Finally, patients are evaluated for the need for activated protein C, and, if appropriate, therapy with the protein is initiated according to BIDMC guidelines.
Data Collection
Initial and serial blood samples for laboratory tests are collected for all patients (Table 5). Blood samples for serum lactate levels are collected hourly until the value is normalized. Numerous studies have established the use of lactate as a marker of tissue hypoxia in shock. Lactate clearance early in the course of therapy is associated with decreased mortality.26 Vital signs are assessed and documented at least every hour and more often as needed at the nurse’s discretion. Vital signs include, but are not limited to, body temperature, respiratory rate, blood pressure including MAP, heart rate, urine output, oxygen saturation, ScvO2, CVP, and neurological checks. Blood samples for assays of arterial blood gases and additional laboratory studies are collected at the discretion of the emergency department and ICU teams.
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Implementation of the MUST Protocol
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Members of the sepsis treatment team obtained approval of the MUST Protocol from the BIDMC critical care executive committee. The executive committee is the governing board for BIDMC’s critical care units. Once approval was received, the team enlisted the support of multiple hospital services to put the protocol into action. The BIDMC equipment and distribution departments procured the ScvO2 catheters required to assess tissue perfusion in the patients to be studied. Hospital Information Systems was enlisted to modify the patient data entry system to allow relevant information to be entered in a single field, thus simplifying data extraction. Team members also worked with personnel from Hospital Information Systems to build a sepsis "order set" (a list of required protocol treatments) to streamline entry of physicians’ orders. The order set was instrumental in guiding the ICU physicians to quickly prescribe all treatments outlined in the protocol with the ease of a single computer mouse click. More importantly, the order set enabled nurses to rapidly acknowledge the orders, expedite all communication with clinicians, and prevent order errors and omissions.
The sepsis team worked with the hospital’s telecommunications specialists to obtain pagers for a core group of caregivers responsible for responding to sepsis-related codes. A system of "virtual pagers" was designed to enable on-call ICU and emergency department physicians to sign into the sepsis emergency response system, thus ensuring they are paged in a timely manner to respond to any sepsis-related code.
Despite the level of complexity and collaboration required to successfully implement the MUST Protocol at BIDMC, the team set aggressive time lines for the project. Total time from initial planning meetings to the official roll out of the protocol was targeted at less than 7 months. While acknowledging the challenges that such a short time frame might represent, all clinicians involved were committed to meeting the projected timetables. Table 6 describes the brief time line for the MUST Protocol.
Staff Education for the Protocol
The education efforts required to implement the protocol were 2-fold: all emergency department and ICU personnel required education on the actual treatment protocol, and ICU and emergency department nursing staff required education on the equipment to be used. This task was daunting, because the sepsis team needed to educate a critical number of the nurses and physicians staffing 46 emergency department and 60 ICU beds. The team used several methods in the education campaign, including the following:
- In-service programs were developed and presented in the units by the clinical nurse specialists in the ICUs and emergency department; included was training on new equipment to be used such as the central venous catheter to measure ScvO2.
- MUST Protocol binders containing copies of the user guide and reference articles were distributed to all units.
- Copies of the protocol were posted on the BIDMC intranet.
- Poster-sized color copies of the sepsis clinical pathway were posted in the emergency department and ICUs.
The education needs of the ICU nurses differed markedly from those of the emergency department nurses. For this reason, the clinical nurse specialists for the 2 groups worked independently to develop and teach required classes. We used 2 models for the education rollout: the emergency department nurses attended a 3-hour in-service program divided into 3 sections consisting of (1) material on pathophysiology and early detection of sepsis; (2) presentation of the study by Rivers et al10 (early goal-directed therapy) and principles behind the protocol; and (3) information on new equipment, monitoring procedures, and documentation. The program was presented "off shift" as part of a continuing education unit initiative. In addition, approximately 75 prehospital providers were also educated within the first 6 months of initiation of the protocol to promote general knowledge of sepsis and the availability of the MUST Protocol at BIDMC.
The ICU nurses received "on-shift training." The nurse educator developed a short program that was presented on a small-group basis; the program covered the nuances of the protocol, the new catheter, and ScvO2. ICU in-service training was provided during regularly scheduled work hours. Individual support was provided as needed by members of the sepsis team to ensure that the protocol became a part of practice at BIDMC. Nursing competency with the protocol will be verified with a mandatory annual competency test.
Education of physicians was accomplished through grand rounds, in-service training during morning rounds, and continual online training. The sepsis order set in the system for entering physicians’ orders also introduced the physicians to the nuances of the protocol. All treatments, including fluid therapy, medications and dosing, and antimicrobial therapy, are contained in a template that is tailored to individual patients.
Challenges During Implementation
Some of the difficulties encountered during the implementation of the MUST Protocol included educating the large number of staff working various shifts, transferring patients treated by using the MUST Protocol from the emergency department to the ICU in a timely fashion, expediting placement of the ScvO2 catheter; and dealing with problems with equipment.
The team also discovered that the healthcare staff had not been educated on exactly how long a patient was expected to be treated by using the protocol. The team regrouped and decided that for each patient, termination of treatment based on the protocol would be explored daily during rounds. Now, if treatment is still required, the patient remains in the protocol. An order from a physician is required to terminate the protocol. This information was quickly disseminated to the staff.
The education rollout was complicated by the large number of nurses and physicians typically involved in the care of a patient with sepsis. The team planned to initiate the in-service programs 2 weeks before the first anticipated use of the protocol so that caregivers would be able to quickly use the knowledge gained. As in most healthcare education, the requirement for staffing 7 days a week, 24 hours a day presented the challenge of trying to reach personnel on all shifts within the short 2-week time frame. During the first months of implementation of the protocol, nurses caring for patients being treated according to the protocol had questions. Members of the sepsis team made themselves available via pager to provide the support needed. This support was considered imperative for successful implementation of the protocol within the specified time line. Support provided included fielding telephone calls, directing staff to online resources or MUST protocol binders, and working side-by-side with nurses at the bedside as patients were admitted.
Currently, team members are exploring possible solutions to improve the time to initiation of treatment. For example, shifting the responsibility for the placement of catheters (currently the responsibility of the emergency department team) to whoever can get it done quickly is being considered. BIDMC opened an additional 7-bed ICU to increase the total number of critical care beds in an attempt to have "sepsis code beds" readily available. Emergency department nurses have continued to administer antibiotics and the initial fluid bolus immediately by using a peripheral intravenous catheter rather than delay treatment until the central catheter is placed.
Equipment challenges centered on tracking cables and monitors used for assessment of ScvO2 as patients were transferred from the emergency department to multiple ICUs. For each patient, the central venous catheter is connected to the patient’s monitor via a fiber-optic cable that enables continuous display of ScvO2 values. This cable travels with the patient to the ICUs because calibration data is stored in the cable. Some difficulties have been experienced with returning cables to the emergency department for use on subsequent patients. This problem is complicated by the fact that BIDMC has ICUs on 2 separate campuses, requiring that some patients be transported via ambulance. To fix this problem, we adopted a system in which an extra cable is swapped out by the emergency department and ICU teams during transfer to the ICU. Additional cables were purchased to help alleviate this problem.
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Conclusion
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Sepsis continues to be common in patients and is associated with a high mortality rate despite advances in critical care in the past 2 decades. According to predictions, the incidence of sepsis and septic shock will increase dramatically in the years to come because of the so-called graying of America and the increased occurrence of chronic disease and HIV infection.1 These factors, coupled with the improved ability to diagnose and identify sepsis, will lead to an even greater challenge for caregivers.
The multidisciplinary sepsis team at BIDMC has taken proven therapies for the treatment of sepsis and incorporated them into an evidence-based clinical pathway that is used by nurses. The team’s goals were to expedite detection of patients at risk for sepsis and to initiate early goal-directed therapy for these patients. Collaborative efforts and institutional acceptance of the MUST protocol led to the successful development and implementation of the protocol. The multidisciplinary sepsis team met bimonthly to implement the protocol and now meets on a periodic basis. The agenda includes an update on the number of patients treated by using the protocol and any issues or challenges, for example, the need to provide education on the protocol as the ICUs and emergency department acquire new staff members. The team also discusses future directions. Team members are currently looking at the feasibility of early recognition of sepsis in patients in the medical-surgical inpatient units.
As advances occur in the treatment of patients with severe sepsis and new interventions are proved effective, members of the sepsis team at BIDMC expect to modify the MUST Protocol accordingly. We hope that this new protocol, as it exists today and as it evolves, will improve survivability for patients with sepsis and decrease related healthcare costs.
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Acknowledgments
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We thank Nathan Shapiro, MD, MPH, J. Woodrow Weiss, MD, and Michael Howell, MD, for their ongoing assistance and guidance with this project. We also thank the dedicated nurses and staff of the emergency department and intensive care units at Beth Israel Deaconess Medical Center for their role in the development, implementation, and maintenance of the protocol. This project was funded in part by a grant from Edwards Life-sciences, Irvine, Calif.
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References
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- Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29: 1303–1310.[Medline]
- Kochanek KD, Smith BL. Deaths: preliminary data for 2002. Natl Vital Stat Rep. 2004;52 (13):1–47. Also available at: http://www.cdc.gov/search.do?action=search&queryText=National+Vital+Statistics+Report+2004&x=9&y=12. Accessed March 13, 2006.
- Arias E, Anderson R, Hsiang-Ching K, et al. 2001 heart disease and stroke statistics update. Natl Vital Stat Rep. September 18, 2003;52(3):39. Also available at: http://www.cdc.org/nchs/data/nvsr/nvsr52/nvsr52_03.pdf. Accessed March 24, 2006.
- American Cancer Society. Statistics for 2001. Available at: http://www.cancer.org/docroot/STT/stt_0_2001.asp?sitearea=STT&level=1. Accessed March 15, 2006.
- Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med. 1999;340: 207–214.[Free Full Text]
- Bone RC, Balk RA, Cerra FB, et al. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:1644–1655.[Abstract/Free Full Text]
- Kleinpell R. Advances in treating patients with severe sepsis: Role of drotrecogin alfa (activated). Crit Care Nurse. June 2003;23:16–29.[Free Full Text]
- Balk RA. Severe sepsis and septic shock: definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000;16:179–192.[Medline]
- Ahrens T, Vollman K. Severe sepsis management: are we doing enough? Crit Care Nurse. October 2003;23(5 suppl):2–15.[Medline]
- Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377.[Abstract/Free Full Text]
- Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709.[Abstract/Free Full Text]
- Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367.[Abstract/Free Full Text]
- Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydro-cortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002; 288:862–871.[Abstract/Free Full Text]
- The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000; 342:1301–1308.[Abstract/Free Full Text]
- Hack CE, Zeerleder S. The endothelium in sepsis: source of and target for inflammation. Crit Care Med. 2001;29(7 suppl):S21–S27.[Medline]
- Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med. 1999;27:639–660.[Medline]
- Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28:2758–2765.[Medline]
- Fowler RA, Rizoli SB, Levin PD, Smith T. Blood conservation for critically ill patients. Crit Care Clin. 2004;20:313–322.[Medline]
- Simon D, Trenholme G. Antibiotic selection for patients with septic shock. Crit Care Clin. 2000;16:215–231.[Medline]
- Riedemann NC, Guo RF, Ward P. Novel strategies for the treatment of sepsis. Nat Med. 2003;9:517–524.[Medline]
- Yildiz O, Doganay M, Aygen B, Guven M, Keleutimur F, Tutuu A. Physiological-dose steroid therapy in sepsis [ISRCTN36253388]. Crit Care. 2002;6:251–259.[Medline]
- Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ. 2004;329:480.[Abstract/Free Full Text]
- Tuschschmidt J, Fried J, Astiz M. Elevation of cardiac output and oxygen delivery improves outcomes in septic shock. Crit Care Med. 1992;102:216–220.
- Gallagher EJ, Rodriguez K, Touger M. Agreement between peripheral venous and arterial lactate levels. Ann Emerg Med. 1997; 29:479–483.[Medline]
- Shapiro N, Howell M, Talmor D, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005;45:524–528.[Medline]
- Nguyen HB, Rivers E, Knoblich BP, et al. Early lactate clearance is associated with improved outcomes in severe sepsis and septic shock. Crit Care Med. 2004;32:1637–1642.[Medline]
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Background of the Protocol
BIDMC Protocol
