Sepsis Case File

Sepsis Case File

Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 19

A 59-year-old woman with a history of Type 2 diabetes mellitus was found unconscious at home by her family members. In the emergency center, she was noted to have a temperature of 38.6°C, pulse rate of 112 beats/minute, blood pressure of 96/50 mm Hg, and respiratory  rate of 26  breaths/minute. After 2 L of nor mal saline, the patient became more alert and began to answer questions more  appropriately.  Laboratory  values reveal WBC 26,000/mm3,  hemoglobin 12 g/dl,  normal platelet count, and a serum glucose level of 280 mg/dL. A Foley catheter was  placed and showed return of concentrated and cloudy urine. The  urinalysis revealed 50 WBC per high-power field. A CT scan of the abdomen without contrast

revealed no free fluid in the abdomen and an inflamed right kidney with perinephric fat stranding. Shortly after the patient was transferred to the ICU, her nurse notifies you that her blood pressure is 78/50 mm Hg and heart rate is 120 beats/minute. 

⯈What is the most likely diagnosis?

⯈What are the priorities in this patient's management?

⯈How would you monitor and support this patient's status?

ANSWER TO CASE 19:

Sepsis

Summary: A 59-year-old diabetic woman is found to be unconscious, febrile, with tachycardia and hypotension. Laboratory analysis reveals a leukocytosis with likely urinary tract infection, and imaging shows involvement of the upper genitourinary system. In the ICU, she develops sudden hypotension and tachycardia. 

• Most likely diagnosis: Acute urinary tract infection related sepsis and septic shock. 
• Priorities in management: Fluid resuscitation and antimicrobial therapy. 
• Monitoring and support of organ perfusion: Intravascular fluid status can be assessed and monitored with CVP catheters or echocardiography. Mean arterial pressure and mixed-venous O2 measurements are helpful to determine patient's responses to therapy. The patient's mental status, urine outputs, and serum lactate levels during the course of resuscitation are also useful indicators of response to resuscitation. Specific monitoring and support guidelines are available in the Surviving Sepsis Campaign publications.

ANALYSIS

Objectives

1. To learn the guidelines and principles for the management of septic patients.
2. To learn the monitoring and strategies for patients with septic shock.
3. To learn the pharmacologic support for patients with septic shock.
4. To learn the role of glucocorticoid therapy for septic shock.

Considerations

This patient is suffering from shock. Shock is defined as inadequate oxygen delivery to meet the patient's tissue metabolic demands. Her initial altered mental status and concentrated urine are overt signs of inadequate end organ perfusion. There are many ways to classify shock. One useful way to think about the etiologies of shock is to divide them into hypovolemic, cardiac, or distributive processes. Hypovolemic shock is caused by hemorrhage or dehydration. Cardiac processes include intrinsic cardiac dysfunction as well as extrinsic causes such as tamponade or tension pneumothorax. In contrast, sepsis is a distributive process caused by acute vasodilation without an accompanying increase in fluid volume. The acute vasodilation leads to an increase in the capacitance of the circulatory system without an increase in volume, leading to a relative hypovolemia. Other distributive causes of shock include anaphylaxis, neurogenic shock, and third spacing seen with systemic inflammation. Sepsis is related to the systemic inflammatory response syndrome (SIRS) , which is characterized by hypo or hyperthermia (temperature <36°C or >38°C) , tachycardia, tachypnea, leukocytosis, or leukocytopenia. Sepsis can be diagnosed when the features of SIRS are present and an infection is the suspected cause. The diagnosis of sepsis does not necessarily mean that shock is present. Septic shock is the diagnosis when there is ongoing hypotension despite fluid resuscitation. Antimicrobial therapy should be initiated to address the infectious process. The initial approach toward the correction of hypotension is to restore intravascular volume with crystalloid administration, and once this is accomplished, persistent hypotension is further addressed with the addition of vasoactive pharmacologic agents and corticosteroids as indicated.

Approach To:

Sepsis

DEFINITIONS

SHOCK: Inadequate oxygen delivery to meet the needs of the body's tissues.

CENTRAL VENOUS PRESSURE: The pressure measured in the superior vena cava reflecting right ventricle end diastolic pressure. It is measured with a centrally inserted venous catheter usually inserted in the internal jugular or subclavian vein. CVP is used clinically to assess volume status in critically ill patients. The CVP is not reliable in patients with tricuspid valve disease.

SIRS: The systemic inflammatory response is a clinical syndrome describing the derangement of the body's inflammatory response. A patient with 3 or more of the findings below meets criteria for the diagnosis of SIRS:

• Temperature <3 6°C or >38°C 
• Heart rate >90 beats/minute 
• Respiratory rate >20 breaths/minute  
• White blood cell count >12,000 or <4,000/mm³

SEPSIS: When the etiology of SIRS is presumed to be infectious in origin, the diagnosis of sepsis is made.

SEVERE SEPSIS: Sepsis with at least 1 organ system dysfunction.

SEPTIC SHOCK: Septic shock is present when there is ongoing hypotension despite fluid resuscitation.

EARLY GOAL-DIRECTED THERAPY: A treatment strategy for sepsis with the goal of rapid restoration of tissue perfusion by manipulation of cardiac preload, afterload, contractility as well as oxygen-carrying capacity.

CLINICAL APPROACH

Guidelines and Principles for the Management of Septic Patients

There is a spectrum of severity of sepsis. Uncomplicated sepsis may be caused by gastroenteritis or influenza, and may only require supportive care with or without antibiotic therapy. Severe sepsis carries a mortality of 25% to 30%. Septic shock is the most severe form of sepsis where mortality can be as high as 50%.

There are 2 main treatment goals in the approach of septic shock: (1) address the source of the infection, and (2) restore perfusion to the tissues to prevent reversible and irreversible organ injuries. Addressing issues number 1 and 2 listed above should occur simultaneously and as soon as the patient is encountered. Randomized trials have shown that patient survival is improved with early intervention, so patients who meet criteria for the diagnosis of septic shock should be treated as rapidly as possible even if that means starting treatment in the emergency department rather than in the ICU.

Therapy is guided by the information gained from continuous monitoring. Since the vasodilation associated with sepsis may produce relative hypovolemia and distributive shock, aggressive fluid resuscitation may be needed to restore intravascular volume and blood pressure. The first goal is to achieve a CVP of 8 to 12 mm Hg, a mean arterial pressure (MAP) of >65 mm Hg, and urine output of >0.5 mL/kg/h. Sometimes this can be achieved with fluids alone. However, if fluids alone do not achieve these goals, a vasopressor may be needed. One of the targets of resuscitation is to improve central venous oxygen content (Cvo2) to >70%; if this target is not achieved with fluids, blood transfusions can be given to maintain an appropriate hematocrit. In some patients with severe primary cardiac dysfunction, dobutamine infusion may be initiated to improve cardiac output, Cvo2, and tissue oxygen delivery.

While the patient is being resuscitated, the source of their infection needs to be identified. Antibiotics should not be withheld during the investigative period. Empiric, broad,spectrum antibiotics should be started within 1 hour of recognition of septic shock. The workup includes obtaining blood, urine, and sputum cultures as well as any other appropriate cultures. Imaging may be required to identify other etiologies such as pneumonia or intra-abdominal infections. Once the source of the infection is identified, antibiotic therapy can be tailored based on cultures and antibiotic-resistance profiles.

Monitoring and Strategies for Patients with Septic Shock

The treatment of shock requires continuous monitoring of the hemodynamic status. A central venous catheter can monitor central venous pressure (CVP) as well as Cvo2 which reflects overall oxygen demand and consumption. A low Cvo2 suggests inadequate oxygen delivery to the tissue beds. An arterial catheter is often placed to monitor blood pressure and more specifically mean arterial pressure. Finally a Foley catheter is used to ensure adequate urine output, which reflects end organ perfusion.

In some instances a Swan-Ganz catheter, also known as a pulmonary artery catheter (PAC) may be used to obtain more information about cardiac status. For instance the PAC can be used to determine the cardiac filling pressures, cardiac output, and systemic vascular resistance. The utility of PAC in critically ill patients is controversial, specifically whether it improves survival. Some of the variables obtained by the PAC can also be determined by echocardiography. Laboratory analysis can also help determine the adequacy of resuscitation. For instance, serial blood lactate levels can be used to monitor the response to treatment. Decreasing trend in lactate levels may indicate that tissue oxygenation is being restored. Similarly, base excess on the arterial blood gas should normalize if oxygen delivery to the tissues is improving.

Pharmacologic Support for Patients with Septic Shock

A primary therapeutic goal in the treatment of septic shock is to restore tissue oxygenation. This is achieved through optimization of preload, cardiac contractility, afterload, and oxygen carrying capacity. While fluid resuscitation and blood transfusions can improve preload and oxygen-carrying capacity, in severe cases additional pharmacologic support may be required to improve cardiac contractility and afterload.

In hypotension that is unresponsive to fluids, vasopressor therapy is needed. When the MAP is low, auto-regulation of blood pressure to the tissue beds is impaired such that perfusion is entirely dependent on the blood pressure. A vasopressor can improve perfusion pressure and maintain blood flow to the tissues. The Surviving Sepsis Campaign recommends norepinephrine (Levophed) or dopamine at the lowest dose necessary to maintain tissue perfusion. Epinephrine may be given if an additional agent is needed. The assessment of the adequacy of tissue perfusion can be determined using blood pressure, Cvo2, urine output, normalization of blood lactate concentrations, and normalization of base excess on arterial blood gas. Some patients with septic shock do not respond to vasopressors due to relative vasopressin deficiency and would benefit from the addition of vasopressin at a constant infusion rate of 0.03 U/min. Dobutamine is a β-agonist that increases cardiac contractility and therefore increases cardiac output. Dobutamine is given when the Cvo2 is low or when myocardial dysfunction is suspected based on elevated filling pressures or low cardiac output. By increasing cardiac output, oxygen delivery to the tissues may be improved in these individuals.

The Role of Glucocorticoid Therapy in Septic Shock

Some critically ill patients have a relative adrenal insufficiency and may benefit from glucocorticoid supplementation. The randomized controlled French multicenter trial involving septic patients with persistent hypotension after appropriate fluid and vasopressor therapy demonstrated improvements in shock reversal and a reduction in mortality when patients received corticosteroids. It is not necessary to prove that a patient has adrenal insufficiency with cortisol stimulation testing prior to giving supplementation. Subsequently, another large European randomized controlled trial (CORTICUS) showed that septic patients who did not require vasopressors did not benefit from corticosteroids treatments, therefore suggesting that patient selection criteria for corticosteroids treatment in the ICU are very important.

CLINICAL CASE CORRELATION

• See also Case 3  (Scoring System/Patient Prognosis), Case 17 (Meningitis/Encephalitis), Case 18 (Antibiotics), and Case  20 (Immune-Compromised Patient With Sepsis).

COMPREHENSION QUESTIONS

19.1  A 52-year-old man presents with right upper quadrant pain and jaundice. In the emergency department he is found to have a fever of 39.2°C, a heart rate of 112 beats/minute, and a blood pressure of 92/40 mm Hg. He has not urinated for 12 hours. He is tender in the right upper quadrant and has a leukocytosis of 19,000/mm³. Which of the following is the best next step in his treatment?

A. Admission to the intensive care unit

B. Right upper quadrant ultrasound

C. Intravenous fluid administration

D. Placement of a pulmonary artery catheter

E. Place a Foley catheter for urine output monitoring

19.2  A 56-year-old woman is admitted with pneumonia and suspected sepsis. Which of the following is the most appropriate set of therapeutic endpoint in the treatment of sepsis?

A. Central venous oxygen >70%, urine output >0.5 mL/kg/h, mean arterial pressure of >85 mm Hg

B. Central venous pressure of >4 mm Hg, urine output >0.5 mL/kg/h, mean arterial pressure >55 mm Hg

C. Central venous oxygen >70%, urine output >10 mL/kg/h, central venous pressure 8 to 12 mm Hg

D. Central venous pressure of 8 to 12 mm Hg, temperature <38.5°C, mean arterial pressure >55 mm Hg

E. Central venous pressure of 8 to 12 mm Hg, urine output >0.5 mL/kg/h, mean arterial pressure >65 mm Hg

19.3  A 62-year-old woman is diagnosed with sepsis due to an intra-abdominal abscess from perforated diverticulitis. While awaiting CT-guided drainage of the abscess what is the best way to treat her infection?

A. Start broad-spectrum antibiotics now.

B. Start antibiotics based on Gram stain from the abscess fluid.

C. Wait to start antibiotics until blood culture results return.

D. Only give antibiotics if she does not improve after drainage of the abscess.

E. Once CT-guided drainage is performed, there would be no need for antibiotics therapy.

ANSWERS TO QUESTIONS

19.1  C. This patient meets the criteria for the diagnosis of SIRS given his fever, tachycardia, hypotension, and leukocytosis. Additionally his clinical presentation is consistent with infectious cholangitis. Since he meets the criteria for SIRS and an infection is suspected, the diagnosis of sepsis should be made, furthermore his ongoing hypotension and low urine output indicate that he is in septic shock. Early goal-directed therapy with the goal of restoring tissue oxygen delivery improves survival from sepsis, so the first step in the treatment of this patient should be fluid resuscitation. Antibiotics should be initiated within 1 hour of presentation. After fluids have been started, monitors for CVP and blood pressure can be placed. Diagnosing the source of his infection should be done as well but a right upper quadrant ultrasound is not the initial step in his treatment. While he may ultimately require admission to the ICU, therapy should not be delayed while awaiting transfer to the ICU.

19.2  E. The goals of therapy for early goal-directed treatment of sepsis reflect the need to restore oxygen delivery to the tissues. Temperature is not an endpoint used to measure the adequacy of tissue oxygenation. Central venous pressure allows for an assessment of overall fluid status, a CVP <8 is consistent with hypovolemia, whereas a CVP of 8 to 12 mm Hg is desired. Adequate urine output ( >0.5 mL/kg/h) indicates good end organ perfusion. Normal central venous oxygen saturation ( >70% ) similarly implies adequate oxygen delivery to the end organs. A mean arterial pressure of >65 mm Hg is the target.

19.3  A. In septic patients, institution of early antibiotic therapy, within 1 hour of diagnosis, is very important. While cultures should be obtained, it is not necessary to prove that infection exists or to identify the infecting organism before starting therapy. It is better to start broad-spectrum antimicrobials initially and then tailor them when culture data is available or stop them entirely if no source is identified.

CLINICAL PEARLS

⯈ Sepsis is diagnosed when there are 2 or more criteria for SIRS  and an infection is suspected. 

⯈ Rapid reversal of hypoperfusion improves survival in sepsis. 

⯈ Treatment of sepsis involves fluid administration, vasopressor therapy, blood transfusions as needed, antibiotics, and infectious source control.

References

Dellinger RP, Levy M M , Carlet JM, et a l . Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;3 6 : 296-3 2 7 . 

Holcroft JW, Trunkey DO, Carpenter MA. Shock. American College of Surgeons. 6th e d . N e w York, NY: WebMD Publishing; 200 7 . 

Rivers E, Nguyen B, Havstad S, et a l . Early goal-directed therapy i n the treatment o f severe sepsis and septic shock. N Eng! ] Med . 200 1 ;345 : 1368- 1 3 7 7 . 

Surviving Sepsis Campaign. http://www.survivingsepsis.org, accessed July 2, 20 1 3 .

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