◆ Early identification of the patient with sepsis facilitates the delivery of appropriate treatment.
◆ The use of screening tools and algorithms may help with identification of sepsis patients.
◆ Delivery of rapid empiric antibiotics directed at the most likely source and organisms in conjunction with infection source control improves patient outcomes.
◆ Early aggressive therapy directed at targeted measures of perfusion do not provide additional benefit if early antibiotics and fluids are successfully delivered.
◆ Clinicians must be aware of potential complications of therapy, and should take precautions to limit nosocomial complications.
The inciting insult that leads to sepsis necessarily involves an infection. Thus, the initial strategy for treating a patient with sepsis involves identifying the source and site of the infection, sending off cultures and rapidly treating with antibiotics [1,2]. In many patients, source control of the infection, such as removing an infected catheter or draining an abscess, is also required. As the previous chapter has noted, the absence of a biomarker for sepsis requires that the treating clinician have a high index of suspicion for sepsis in critically ill patients.
Sepsis patients require prompt delivery of antibiotics directed at the most likely causative organisms. It is useful to have appropriate cultures drawn to assist with subsequent tailoring of antibiotics, but delivery of such antibiotics should not be excessively delayed in order to obtain these cultures. Since the results from cultures take hours to days, the selection of antibiotics should be driven by the site of infection, host susceptibility, and the likelihood of exposure to resistant organisms. In general, patients with recent exposure to the health care system including hospitalization, nursing home residence, or visits to dialysis or chemotherapy clinics will be at risk for resistant organisms. The prevalence of resistant organisms in the community also needs to be considered when selecting initial empiric therapy, in addition to local sensitivity patterns. The site of infection: lungs, abdomen, urine, bloodstream, or central nervous system will also assist with the initial antimicrobial choice .
In general, most patients with sepsis require broad coverage including both Gram-positive and Gram-negative organisms. Using two different antimicrobial agents to ‘double cover’ Gram-negative organisms remains controversial, and, in the absence of extreme local resistance patterns or diseases such as cystic fibrosis, is not generally recommended .
Delay in appropriate antibiotic infusion has been associated with increased patient mortality . Current treatment goals for hypotensive sepsis patients include the administration of effective antibiotics within an hour of hypotension for hospitalized patients . This need for rapid delivery requires that the physician pay attention to the mechanics of ensuring that any order for antibiotics is expeditiously communicated to the nurse and pharmacy so that the medication ordered is delivered promptly to the patient.
Duration of antibiotic therapy should be driven by the site of infection, likely causative organisms, and clinical response to therapy. Patients who are in shock will often require longer courses of therapy than those patients who are clinically improving. In the absence of clinical deterioration, a shorter course of antibiotics of 7–8 days appears to be as effective as a longer course of 15 days for patients with ventilator associated pneumonia without resistant Gram-negative organisms . Biomarkers such as procalcitonin are a potential option to use as part of an antibiotic de-escalation strategy . Other strategies to limit length of therapy include use of clinical scores for pneumonia. While these strategies to limit antibiotic use have been clearly shown to decrease risk of complications and decrease exposure to antibiotics, they have not shown to effect patient mortality [3,7]. At this time, we do not recommend the use of biomarkers as a trigger to withhold antibiotics for critically ill patients with presumed sepsis. Most clinicians will, for patients with severe sepsis start broad spectrum antibiotics and modify the type and duration of antibiotics based on results from cultures and the patient’s clinical response.
Infection source control
In conjunction with effective antibiotics, infection source control is an essential part of sepsis therapy. Both surgical and interventional radiological procedures should be considered in a patient with a closed space infection such as an abscess or empyema; those patients with an indwelling catheter that is suspected of being infected should have it removed as soon as alternate access is obtained. Treating through an infected catheter without its removal in patients with severe sepsis or septic shock is not recommended. Some sepsis patients have co-morbidities such as coagulopathy or shock that may complicate the ability to achieve source control, and the treating clinician may need to treat these co-morbidities in order to facilitate source control
Early aggressive therapy
Supportive therapy buys time for the patient’s host defence system to work in conjunction with antibiotic therapy to treat severe infections. Since the host response to infection often leads to vascular leak and decreased filling pressures, patients with sepsis require infusion of IV fluids to increase cardiac output and restore systemic perfusion of vital organs as a first line supportive treatment. There are many choices for types of fluid therapy: crystalloid fluids are most commonly used, and usually require higher doses than colloids . Initial therapy of a severe sepsis patient should include a rapid infusion of crystalloids of at least 15–30 cc/kg, with many patients requiring additional boluses . The largest randomized trial comparing crystalloid to colloid therapy in critically ill patients did not show a benefit to use of colloid therapy compared with crystalloids . While no type of fluid therapy has been proven to be superior in patients with sepsis, the use of hydroxyethyl starches such as pentastarch and hetastarch have been shown to be harmful and are not recommended [8,10]. Patients with more severe forms of sepsis such as septic shock will require large amounts of fluid resuscitation both initially and over the first 24 hours of therapy, in doses that may approach 8–9 litres of crystalloid in over a 24 hour period .
In addition to following the patients vital signs in response to therapy, many patients receive assessment of filling pressures such as central venous pressure, and targets of resuscitation such as venous oxygen saturation or lactate (See Box 296.1). Use of early aggressive strategies based on treatment goals including specific targets do not provide additional benefit if early antibiotics and fluids have been effectively delivered.. Failure to reach treatment goals should prompt both re-evaluation of initial diagnosis, as well as consideration of additional therapy to both improve cardiac output and peripheral perfusion as well as limitation of oxygen consumption (See Fig. 296.1) [12,13]. While complicated algorithms have been used for acute care of the sepsis patient, it is not known which patient’s part of the algorithms are most helpful. We therefore suggest using some clinical target such as lactate clearance or central venous oxygen saturations in addition to usual measures of vital sign monitoring such as following blood pressure, pulse, and urine output.
Delayed aggressive care of the sepsis patient that waits until the patient is stabilized in the ICU does not improve patient outcomes . For most patients the aggressive phase of therapy should be continued for at least 6 hours and perhaps up to 24 hours. It is reasonable, if a patient is responding to fluid loading or additional therapies to increase oxygen delivery or decrease oxygen consumption, to continue these therapies beyond this 24 hour time point. If the patient does not respond to therapies to increase oxygen delivery such as adding additional fluids, transfusing packed red cells or adding an inotrope, the clinician will need to balance the risk of adding new goal directed therapies against any potential risks in an individualized fashion.
Supportive therapy for sepsis patients
Patients with sepsis are at risk for developing complications such as respiratory failure, acute respiratory distress syndrome (ARDS), acute kidney injury, disseminated intravascular coagulation, and delirium. Each of these complications of sepsis may require specific supportive therapy. Patients with sepsis who require positive pressure ventilation should receive therapy designed to both rest respiratory muscles and limit work of breathing including mechanical ventilation, pain and symptom control, and in many patients endotracheal intubation. Since sepsis patients who develop respiratory failure are at increased risk of developing ARDS, the clinician should choose a ventilator strategy that limits volumes and plateau pressures to decrease the likelihood of developing ventilator induced lung injury and ARDS .
The use of manoeuvers such as the straight leg raise may allow determination of whether additional fluid boluses might be helpful . Once adequate volume resuscitation has occurred, there is little value in infusing additional IV fluids .
Some patients will require use of renal replacement therapy after the development of sepsis induced acute kidney injury. While dialysis will assist with fluid balance and potassium and solute clearance, the use of early or more intensive dialysis does not provide additional benefit over use for specific indications. There is no proven value in using dialysis therapies for clearance of specific inflammatory mediators. Additional support therapies such as nutritional are necessary in many patients, with the enteral route preferred for most.
Limitation of complications for sepsis patients
While early aggressive care of the sepsis patient in the emergency department and ICU may save lives, it is clear that these aggressive treatments are associated with risks including the development of nosocomial infections, delirium, critical illness weakness, stress ulceration, and ventilator induced lung injury . It is important that the clinician carefully consider the risks of therapy when applying therapies. Strategies that may be useful in preventing ICU complications include limiting tidal volume in patients at risk for developing acute lung injury, limiting use of sedation and analgesics and mobilizing patients early in the course of sepsis. Avoidance of hyperglycaemia and hypoglycaemia are important ancillary goals, although the goal glucose level in a patient with sepsis remains controversial. Strategies to prevent nosocomial infections such as catheter checklists and ventilator bundles are also essential.
Response to treatment and continued care
Most patients with severe sepsis and septic shock will require treatment in an ICU where staffing ratios of nurses, physicians, and other caregivers will allow repeated and detailed observation of vital signs and organ perfusion. With early appropriate supportive care and antibiotics patients should demonstrate response to therapy including decreased fever, decreased pulse, and improved organ perfusion, and decreased need for supportive therapies such as mechanical ventilation and vasopressor support. If a patient does not show such clinical improvement, the clinician will need to reconsider whether there is an undrained infectious focus, whether the initial antimicrobial strategy was correct and whether there might be an alternate explanation for the patient’s illness.
When available, culture results should allow tailoring antibiotics based on minimizing side effects, resistance, and costs. Use of clinical biomarkers such as procalcitonin may be helpful in limiting antibiotic length of therapy where available . Since there is little guidance as to the length of therapy for most types of infections, it is reasonable to consider de-escalation of therapies when a patient is clinically improving
Once a sepsis patient with respiratory failure has been stabilized, the clinician needs to consider measures that will lead to expeditious removal of endotracheal tubes and mechanical ventilation. Such measures would include a targeted sedation strategy, such as daily interruption of sedation, often in conjunction with early rehabilitation and mobility strategies, and fluid removal with diuretics in patients off vasopressor support for more than 12 hours [3,18]. Clinical improvement should also prompt consideration of whether other invasive devices such as arterial and venous catheters, as well as urinary catheters are still required. Use of cognitive aids such as checklists to remind clinicians about whether such devices are still required has been shown to be an effective technique.
Prevention of long-term complications of sepsis
While initial care of the sepsis patient requires aggressive and often invasive therapy, many sepsis patients will transition out of the ICU to regular wards. Many sepsis patients will develop ICU acquired weakness, delirium, and depression that will persist after ICU discharge . While strategies designed to limit sedation and mobilize ICU patients may get them off the ventilator earlier, it is not yet known whether these strategies will limit the development of weakness or delirium .
1. Nguyen HB, Corbett SW, Steele R, et al. (2007). Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Critical Care Medicine, 35(4), 1105–12.Find this resource:
2. Moore LJ, Jones SL, Kreiner LA, et al. (2009). Validation of a screening tool for the early identification of sepsis. Journal of Trauma, 66(6), 1539–46; discussion 46–7.Find this resource:
3. Dellinger RP, Levy MM, Rhodes A, et al. (2013). Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Critical Care Medicine, 41(2), 580–637.Find this resource:
4. Paul M, Silbiger I, Grozinsky S, Soares-Weiser K, and Leibovici L. (2006). Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database of Systematic Reviews, 1, CD003344.Find this resource:
5. Kumar A, Roberts D, Wood KE, et al. (2006). Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Critical Care Medicine, 34(6), 1589–96Find this resource:
6. Chastre J, Wolff M, Fagon JY, et al. (2003). Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. Journal of the American Medical Association, 290(19), 2588–98.Find this resource:
7. Tang BM, Eslick GD, Craig JC, and McLean AS. (2007). Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. The Lancet Infectious Diseases, 7(3), 210–17.Find this resource:
8. Perel P, Roberts I, and Ker K. (2013). Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database of Systematic Reviews, 2, CD000567.Find this resource:
9. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, and Norton R. (2004). A comparison of albumin and saline for fluid resuscitation in the intensive care unit. New England Journal of Medicine, 350(22), 2247–56.Find this resource:
10. Perner A, Haase N, Guttormsen AB, et al. (2012). Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. New England Journal of Medicine, 367(2), 124–34.Find this resource:
11. Packman MI and Rackow EC. (1983). Optimum left heart filling pressure during fluid resuscitation of patients with hypovolemic and septic shock. Critical Care Medicine, 11(3), 165–9.Find this resource:
12. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, and Kline JA. (2010). Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. Journal of the American Medical Association, 303(8), 739–46.Find this resource:
13. Rivers E, Nguyen B, Havstad S, et al. (2001). Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine, 345(19), 1368–77.Find this resource:
14. Gattinoni L, Brazzi L, Pelosi P, et al. (1995). A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. New England Journal of Medicine, 333(16), 1025–32.Find this resource:
15. Li G, Malinchoc M, Cartin-Ceba R, et al. (2011). Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota. American Journal of Respiratory and Critical Care Medicine, 183(1), 59–66.Find this resource:
16. Coudray A, Romand JA, Treggiari M, and Bendjelid K. (2005). Fluid responsiveness in spontaneously breathing patients: a review of indexes used in intensive care. Critical Care Medicine, 33(12), 2757–62.Find this resource:
17. Needham DM, Davidson J, Cohen H, et al. (2012). Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders’ conference. Critical Care Medicine, 40(2), 502–9.Find this resource:
18. Schweickert WD, Pohlman MC, Pohlman AS, et al. (2009). Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet, 373(9678), 1874–82.Find this resource:
19. Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, and Sevransky JE. (2010). Long-term mortality and quality of life in sepsis: a systematic review. Critical Care Medicine, 38(5), 1276–83.Find this resource: