Approach Considerations
Patients with sepsis, severe sepsis, and septic shock require hospital admission. Patients with sepsis who respond to early resuscitation therapy in the emergency department (ED) and show no evidence of end-organ hypoperfusion may be admitted to a general hospital unit, optimally one that has close nursing observation and monitoring. Such patients do not require invasive hemodynamic monitoring and usually do not require admission to an intensive care unit (ICU).
Patients who do not respond to initial ED treatment (ie, who have recurrent hypotension despite adequate fluid challenges) and those who are in septic shock require admission to an ICU for continuous monitoring and continued goal-directed therapy. If an appropriate ICU bed or physician is not available, the patient should be transferred with advanced life support monitoring to another hospital with the available resources.
There is significant controversy surrounding goal-directed therapy (EGDT) in the management of severe sepsis and septic shock. EGDT was previously evaluated in a small, single, randomized trial at a single institution.[70] Subsequently, three newer, large, multicenter randomized trials were performed in the United States (ProCESS [Protocolized Care for Early Septic Shock]),[59] Australia (ARISE [Australasian Resuscitation In Sepsis Evaluation]),[60] and the United Kingdom (ProMISe [Protocolised Management In Sepsis]).[61]
In the ProCESS trial, 1341 patients with septic shock in 31 academic hospital EDs received treatment based on one of three approaches: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or standard care.[71, 72] No significant differences between groups were found for 90-day mortality, 1-year mortality, or the need for organ support.
Similar findings were reported from both the ARISE and the ProMISe trials. Important to note, measuring lactate, targeting ScvO2 values, and insertion of a central venous catheter were not associated with improved outcomes. What was important was the direct and aggressive individualized care each patient received, including early bacteriologic cultures of appropriate sites (eg, blood, urine, sputum), early and correct institution of broad-spectrum antibiotics, restoration of blood pressure, and reversal of evidence of end-organ perfusion. These findings are reasonable when considered within the context of acute care medicine resuscitation principles. Namely, stabilize the patient, reverse the cause of shock, and do no additional harm.
Goals and principles of treatment
The treatment of patients with septic shock has the following major goals:
Start adequate antibiotic therapy (proper dosage and spectrum) as early as possible
Resuscitate the patient, using supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation (hypoperfusion)
Identify the source of infection, and treat with antimicrobial therapy, surgery, or both (source control)
Maintain adequate organ system function, guided by cardiovascular monitoring, and interrupt the progression to multiple organ dysfunction syndrome (MODS)
Management principles, based on the current literature, include the following:
Early recognition
Early and adequate antibiotic therapy
Source control
Early hemodynamic resuscitation and continued support
Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS)
Initial treatment includes support of respiratory and circulatory function, supplemental oxygen, mechanical ventilation, and volume infusion. Treatment beyond these supportive measures includes antimicrobial therapy targeting the most likely pathogen, removal or drainage of the infected foci, treatment of complications, and interventions to prevent and treat effects of harmful host responses. Source control is an essential component of sepsis management.
Venous access
In all cases of septic shock, adequate venous access must be ensured for volume resuscitation. When sepsis is suspected, 2 large-bore (16-gauge) intravenous (IV) lines should be placed if possible to allow administration of aggressive fluid resuscitation and broad-spectrum antibiotics. Central venous access is useful when administering vasopressor agents and in establishing a stable venous infusion site but is not mandatory.
If the hypotension does not respond to a crystalloid fluid bolus of 30 mL/kg (1-2 L) over 30-60 minutes or if fluids cannot be infused rapidly enough, a central venous catheter should be placed in the internal jugular or subclavian vein. This catheter allows administration of medication centrally and provides multiple ports for rapid fluid administration, antibiotics, and vasopressors if needed. It also allows measurement of central venous pressure (CVP), a surrogate for volume status, if CVP measurement capability is available.
If an intravascular access device is suspected as the source of severe sepsis or septic shock, alternative vascular access must be obtained, and the suspect device must then be removed.
Urinary catheterization
An indwelling urinary catheter should be placed. In all patients with sepsis, urine output (UOP), a marker for adequate renal perfusion and cardiac output, should be closely monitored, as should renal function; mortality is greatly increased in patients with urosepsis and severe sepsis or septic shock. Normal UOP in an adult is 0.5 mL/kg/hr or more,[13, 62] equivalent to about 30-50 mL/hr for most adults.
Any abnormalities in UOP should prompt assessment of the adequacy of circulating blood volume, cardiac output, and blood pressure; these should be corrected if inadequate. As with sepsis in other sites, early and appropriate initiation of antimicrobial therapy—as well as identification and management of any urinary tract disorders—is essential.[56]
Intubation and mechanical ventilation
Most patients with sepsis develop respiratory distress as a manifestation of severe sepsis or septic shock. The lung injury is characterized pathologically as diffuse alveolar damage (DAD) and ranges from acute lung injury (ALI)—or mild ARDS, by the Berlin Definition[12] —to moderate or severe ARDS (see Background). These patients need intubation and mechanical ventilation for optimal respiratory support. Intubation should be considered early in the course of progressing severe sepsis and septic shock.
Direct delivery of oxygen into the trachea at a fraction of inspired oxygen (FIO2) of 1 is far superior to delivery via a nonrebreather oxygen mask. Mechanical ventilation, with appropriate sedation, also eliminates the work of breathing as well as decreases the metabolic demands of breathing, which accounts for about 30% of total metabolic demand at baseline.
Alveolar overdistention and repetitive opening and closing of alveoli during mechanical ventilation have been associated with an increased incidence of ARDS. Low−tidal volume ventilatory strategies have been used to minimize this type of alveolar injury. The recommended tidal volume is 6 mL/kg, with plateau pressures kept at or below 30 mL H2 O.[13, 62] Positive end-expiratory pressure (PEEP) is required to prevent alveolar collapse at end-expiration.[73]
Approach ConsiderationsPatients with sepsis, severe sepsis, and septic shock require hospital admission. Patients with sepsis who respond to early resuscitation therapy in the emergency department (ED) and show no evidence of end-organ hypoperfusion may be admitted to a general hospital unit, optimally one that has close nursing observation and monitoring. Such patients do not require invasive hemodynamic monitoring and usually do not require admission to an intensive care unit (ICU).Patients who do not respond to initial ED treatment (ie, who have recurrent hypotension despite adequate fluid challenges) and those who are in septic shock require admission to an ICU for continuous monitoring and continued goal-directed therapy. If an appropriate ICU bed or physician is not available, the patient should be transferred with advanced life support monitoring to another hospital with the available resources.There is significant controversy surrounding goal-directed therapy (EGDT) in the management of severe sepsis and septic shock. EGDT was previously evaluated in a small, single, randomized trial at a single institution.[70] Subsequently, three newer, large, multicenter randomized trials were performed in the United States (ProCESS [Protocolized Care for Early Septic Shock]),[59] Australia (ARISE [Australasian Resuscitation In Sepsis Evaluation]),[60] and the United Kingdom (ProMISe [Protocolised Management In Sepsis]).[61]In the ProCESS trial, 1341 patients with septic shock in 31 academic hospital EDs received treatment based on one of three approaches: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or standard care.[71, 72] No significant differences between groups were found for 90-day mortality, 1-year mortality, or the need for organ support.Similar findings were reported from both the ARISE and the ProMISe trials. Important to note, measuring lactate, targeting ScvO2 values, and insertion of a central venous catheter were not associated with improved outcomes. What was important was the direct and aggressive individualized care each patient received, including early bacteriologic cultures of appropriate sites (eg, blood, urine, sputum), early and correct institution of broad-spectrum antibiotics, restoration of blood pressure, and reversal of evidence of end-organ perfusion. These findings are reasonable when considered within the context of acute care medicine resuscitation principles. Namely, stabilize the patient, reverse the cause of shock, and do no additional harm.Goals and principles of treatmentThe treatment of patients with septic shock has the following major goals:Start adequate antibiotic therapy (proper dosage and spectrum) as early as possibleResuscitate the patient, using supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation (hypoperfusion)Identify the source of infection, and treat with antimicrobial therapy, surgery, or both (source control)Maintain adequate organ system function, guided by cardiovascular monitoring, and interrupt the progression to multiple organ dysfunction syndrome (MODS)Management principles, based on the current literature, include the following:Early recognitionEarly and adequate antibiotic therapySource controlEarly hemodynamic resuscitation and continued supportProper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS)Initial treatment includes support of respiratory and circulatory function, supplemental oxygen, mechanical ventilation, and volume infusion. Treatment beyond these supportive measures includes antimicrobial therapy targeting the most likely pathogen, removal or drainage of the infected foci, treatment of complications, and interventions to prevent and treat effects of harmful host responses. Source control is an essential component of sepsis management.Venous accessIn all cases of septic shock, adequate venous access must be ensured for volume resuscitation. When sepsis is suspected, 2 large-bore (16-gauge) intravenous (IV) lines should be placed if possible to allow administration of aggressive fluid resuscitation and broad-spectrum antibiotics. Central venous access is useful when administering vasopressor agents and in establishing a stable venous infusion site but is not mandatory.If the hypotension does not respond to a crystalloid fluid bolus of 30 mL/kg (1-2 L) over 30-60 minutes or if fluids cannot be infused rapidly enough, a central venous catheter should be placed in the internal jugular or subclavian vein. This catheter allows administration of medication centrally and provides multiple ports for rapid fluid administration, antibiotics, and vasopressors if needed. It also allows measurement of central venous pressure (CVP), a surrogate for volume status, if CVP measurement capability is available.If an intravascular access device is suspected as the source of severe sepsis or septic shock, alternative vascular access must be obtained, and the suspect device must then be removed.Urinary catheterizationAn indwelling urinary catheter should be placed. In all patients with sepsis, urine output (UOP), a marker for adequate renal perfusion and cardiac output, should be closely monitored, as should renal function; mortality is greatly increased in patients with urosepsis and severe sepsis or septic shock. Normal UOP in an adult is 0.5 mL/kg/hr or more,[13, 62] equivalent to about 30-50 mL/hr for most adults.Any abnormalities in UOP should prompt assessment of the adequacy of circulating blood volume, cardiac output, and blood pressure; these should be corrected if inadequate. As with sepsis in other sites, early and appropriate initiation of antimicrobial therapy—as well as identification and management of any urinary tract disorders—is essential.[56]
Intubation and mechanical ventilation
Most patients with sepsis develop respiratory distress as a manifestation of severe sepsis or septic shock. The lung injury is characterized pathologically as diffuse alveolar damage (DAD) and ranges from acute lung injury (ALI)—or mild ARDS, by the Berlin Definition[12] —to moderate or severe ARDS (see Background). These patients need intubation and mechanical ventilation for optimal respiratory support. Intubation should be considered early in the course of progressing severe sepsis and septic shock.
Direct delivery of oxygen into the trachea at a fraction of inspired oxygen (FIO2) of 1 is far superior to delivery via a nonrebreather oxygen mask. Mechanical ventilation, with appropriate sedation, also eliminates the work of breathing as well as decreases the metabolic demands of breathing, which accounts for about 30% of total metabolic demand at baseline.
Alveolar overdistention and repetitive opening and closing of alveoli during mechanical ventilation have been associated with an increased incidence of ARDS. Low−tidal volume ventilatory strategies have been used to minimize this type of alveolar injury. The recommended tidal volume is 6 mL/kg, with plateau pressures kept at or below 30 mL H2 O.[13, 62] Positive end-expiratory pressure (PEEP) is required to prevent alveolar collapse at end-expiration.[73]
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