Sepsis

I. What every physician needs to know.

A. Definition:

The definition of sepsis and the clinical criteria supporting its diagnosis has recently been updated, as have protocols regarding the initial management of sepsis.

Sepsis was originally defined as suspected or known infection with systemic manifestations (≥2 systemic inflammatory response syndrome [SIRS] criteria). In this construct, sepsis would progress along a continuum to severe sepsis, defined as sepsis with organ dysfunction or tissue hypo-perfusion, and then to septic shock, defined as severe sepsis with hypotension (systolic blood pressure [SBP] below 90 millimeters mercury [mmHg] or mean arterial pressure [MAP] below 70 mmHg) refractory to volume resuscitation.

This definition was updated in 2016, in a consensus statement dubbed Sepsis-3, which defines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction is operationalized as a change (≥2) in the Sequential Organ Failure Assessment(SOFA) score. Use of SIRS criteria and the concept of severe sepsis were removed from the definition. Additionally, septic shock as defined by Sepsis-3 is a subset of septic patients who require vasopressors to maintain MAP >65 mmHg and have serum lactate >2 millimoles/Liter despite adequate volume resuscitation.

The hospitalist should be aware of these new definitions and stay current on upcoming validating literature as well as recognize that these new definitions have yet to be incorporated into many hospital protocols or adopted by regulatory agencies, i.e. Center for Medicare and Medicaid Services (CMS), and are not universally accepted by professional societies.

This chapter will incorporate the new definitions and concepts where applicable, but will continue to use former SIRS-based sepsis definitions given widespread familiarity, use in current billing and institutional protocols, and establishment in literature.

B. Epidemiology:

Incidence of sepsis is 3 cases per 1,000 people and it is the most common cause of death in non-coronary intensive care units (ICUs). Mortality can be up to up to 50% in septic shock, and over the last 15 years, sepsis has contributed to 6% of all deaths in United States (US), with an increase in death due to sepsis by 31%, despite vast improvements in care and a decreasing case-fatality rate.

C. Presentation:

Patients with sepsis can present with a wide variety of clinical scenarios, requiring a high index of suspicion. Occasionally, patients may present with organ-specific complaints such as productive cough, diarrhea or dysuria. They may be confused or may complain of weakness, fatigue, or may even have a history of being “found down”. Early recognition and vigilance is paramount to survival in patients with severe sepsis and septic shock. Thus, experts and hospital systems have focused on early warning systems i.e. national early warning system (NEWS) and modified early warning system (MEWS), which incorporate vital signs, oxygenation, mental status and urine output and will often trigger the care team of changes in patient status to prompt assessment.

Evidence Based Medicine (EBM) Key for Hospitalists: Patients who develop sepsis while in the hospital have increased mortality (35%) vs. patients who present with sepsis on admission (12%).

II. Diagnostic Confirmation: Does your patient have SEPSIS?

A. SIRS

Four criteria describe the systemic inflammatory response syndrome:

1. Body temperature less than 36° Celsius © or greater than 38° C

2. Heart rate greater than 90 beats per minute

3. Respiratory rate greater than 20 breaths/minute or partial pressure carbon dioxide (PaCO₂) below 32 mmHg

4. White blood cell count of greater than 12,000 cells/millimeter³ (mm³), less than 4,000 cells/mm³, or greater than 10% immature neutrophils (bands)

SIRS is diagnosed when at least two of these criteria are met, SIRS in the infected patient can be self-limited or progress to severe sepsis and septic shock. Of note, 7/8 patients with sepsis and severe organ dysfunction will have ≥2 SIRS, conversely 1/8 will not.

B. SOFA

SOFA-Score is an assessment of organ function which provides clinical criteria in an infected patient to support the diagnosis of sepsis using a multitude of organ specific variables and can be calculated with readily available online calculators. qSOFA is recommended to be used to risk stratify patient at increased risk of mortality or prolonged ICU stay, and requires no labs: ≥2 of the following: 1. Hypotension 100 mmHg SBP, 2, Altered consciousness, Tachypnea >22 breath/minute are at increased risk of prolonged ICU stay and mortality.

EBM Key: Recent data suggests early warning systems mentioned above which incorporate vital signs, oxygenation, mental status, etc., like NEWS may perform better than conventional SIRS and newer qSOFA in predicting sepsis mortality, and do so earlier in disease course.

Ultimately, consideration of these variables and the patient’s presentation along with physician judgment are at the core of recognition of high-risk septic patients, which is the most important step in sepsis care.

C. What diagnostic tests should be performed?

There is no test that determines if a patient is septic. Rather, sepsis is diagnosed when a patient has suspected infection and has ≥2 SIRS criteria (standard definition) or infection-induced organ dysfunction (new definition.)
Basic laboratory analysis should be performed to assess severity of sepsis and evaluate for a source.
When sepsis is diagnosed, the most common site of infection is the lung, followed by the abdomen and the urinary tract, though a significant amount of patients will have negative bacterial cultures. Lab studies should include:

1. Complete blood count with differential

2. Chemistry panel including magnesium, phosphorus, and glucose

3. Liver function tests

4. Coagulation profile

5. Lactic acid

6. Urinalysis

7. Urine culture

8. Blood cultures x 2 sets, fungal culture if at risk

9. Sputum gram stain and culture if lung source suspected

10. Chest x-ray

11. Electrocardiography (EKG)

12. Arterial blood gas if respiratory status is compromised or severe acidosis suspected

13. Culture any other site that may appear infected (ex stool, cerebral spinal fluid)

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

See above.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The most commonly used imaging study in the diagnosis of sepsis is a chest x-ray. Chest x-rays can provide useful information regarding the possibility of infections (such as pneumonia or empyema) as well as rule out pulmonary edema (which maybe present in cardiogenic shock). Depending on a patient’s initial complaints and and risks, other imaging studies such as an abdominal x-ray (to rule out a perforation) or abdominal computed tomography (CT) scans (to identify possibly abscesses, perforations, bleeding, etc.) may be of value. If meningitis is the suspected cause of sepsis, a CT scan of the head may be indicated followed by a lumbar puncture.

III. Default Management.

The initial management of sepsis is aimed at stabilizing the patient, assessing for and preventing further end-organ dysfunction and initiating antibiotics. Management of severe sepsis and septic shock aims at maximizing tissue perfusion with intravenous crystalloids and vasopressors and supportive care. These goals are protocolized via Surviving Sepsis Campaign and CMS/National Quality Forum’s protocolized care known as the Sepsis Bundle.

A. Immediate management.

Stabilization of patient:

Assess the patient’s mental status to determine whether or not they can protect their airway – if unable to protect airway then intubate immediately if hemodynamically stable.
Ensure patient has adequate intravenous access (preferably central venous access in case patient needs vasoactive agents); if patient is in the intensive care unit, place an arterial line for close blood pressure monitoring.
Initiate Sepsis Bundle:
3-hour goal: within 3 hours of diagnosis of severe sepsis: obtain blood cultures, start antibiotics, and check serum lactate.

If patient develops septic shock, see 6-hour portion of bundle below.

EBM Key: Adherence to sepsis bundle has been shown to improve mortality and lower costs.
Monitor vital signs very closely:
Normalize blood pressure with use of crystalloids or colloids. Administer fluids (1-2 liters [L]) to the patient with severe sepsis. Administer 30 milliliters/kilogram (ml/kg) of crystalloids over 30 minutes to the patient presenting with septic shock or in patients who become hypotensive (SBP 90 mmHg) after initial fluid challenge of 1-2L crystalloids.

If patients remain hypotensive despite fluid resuscitation, they are in septic shock. Obtain central venous access and use vasopressors to keep MAP greater than 65 mmHg. Use Norepinephrine as initial agent and/or vasopressin as adjunct and then epinephrine as next agent. Other agents such as phenylephrine and dobutamine can be considered. Dopamine has been shown to have increased mortality compared to Norepinephrine in septic shock.

In septic shock that has not responded to vasopressor therapy, there may be some benefit to empiric stress dose steroids. Send a cortisol stimulation test and give patients empiric stress doses of steroids until the results of the test are back.

Start broad spectrum antibiotics within one hour of assessing the patient.

EBM Key: Septic shock mortality worsens by almost 8% for every 1-hour delay in antibiotics.

Blood cultures should always be drawn prior to administration of antibiotics.

Obtain blood, urine, and sputum cultures; culture other sites if clinically indicated.

Narrow antibiotic coverage if infectious etiology identified on culture.
Reverse any electrolyte and glucose abnormalities
Conservative red blood cell transfusion transfusion thresholds are appropriate (transfuse when hemoglobin 7 grams/deciliter)

Monitor all patients very closely for changes in vital signs, hemodynamics status. Monitor response to fluids and be aware of multifactorial (i.e.cardiogenic + septic) shock. Use qSOFA to help determine who requires higher level of care.

B. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Measure serum lactic acid at diagnosis and repeat (within 6 hours) if initial level is elevated.
6 hour Bundle:

If patient has diagnosis of septic shock→ Within 6 hours:

Repeat volume status and tissue perfusion assessment consisting of either:

A focused exam including:

Vital signs, AND
Cardiopulmonary exam, AND
Capillary refill evaluation, AND
Peripheral pulse evaluation, AND
Skin examination

OR Any two of the following four:

Central venous pressure measurement
Central venous oxygen measurement
Bedside cardiovascular ultrasound
Passive leg raise or fluid challenge

*Document this reassessment in medical record

Follow any end organ abnormality (Creatinine, transaminases, troponin) until improvement is seen. Patient may require advanced airway, renal replacement therapy, blood product transfusions, etc. and ongoing reassessment should be completed to ensure response to resuscitation and antibiotic therapy to ensure effective treatment.

C. Long-term management.

There is no chronic form of sepsis.

D. Common Pitfalls and Side-Effects of Management

Monitor patients that are on vasoactive agents very closely for arrhythmias and skin necrosis.
Excessive Fluid resuscitation has been associated with increased need for renal replacement therapy.
Hypotension and/or Kussmaul’s respirations in severe acidosis that are present in the septic patient may lead to peri-intubation arrest if not recognized and managed prior to intubation attempt.
Early goal directed therapy (EGDT) parameters for monitoring central venous oxygenation (SCVO₂) and central venous pressure (CVP) as well as EGDT-specific transfusion thresholds have been relaxed from Sepsis Bundle owing to no increased benefit from EGDT protocols from recent sepsis clinical trials and they will increase ICU utilization.

IV. Management with Co-Morbidities

A. Pulmonary edema

Conservative use of fluids is reasonable; care should be taken to provide necessary volume resuscitation and monitoring of volume status and response to fluids; involve intensivists and proceed cautiously.

B. Cirrhosis

Septic cirrhotic will have worse prognosis than general public with mortality up to 60-100% in cirrhotic septic shock. Resuscitation with albumin over crystalloids likely contributes to observational data of improved survival. Steroid use in the shocked cirrhotic is controversial because of increase in shock relapse and gastrointestinal (GI) bleeding.

C. ESRD (end-stage renal disease)

Septic dialysis patients will have worse prognosis than general public. 100- to 300-fold rates of sepsis mortality has been described. There are no studies available to adequately assess fluid resuscitation strategies in ESRD patient with shock. Excessive fluids are not advised, as this can cause renal failure in the septic patient without ESRD.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

For transitions of care, ensure the cross-covering provider is familiar with reassessment of organ perfusion and volume status in 3 and 6-hour sepsis bundle as this can improve mortality. Ensure code status is discussed and updated.

B. When is the Patient Ready for Discharge.

Discharge is contingent on stabilization of vital signs and resolution of organ failure. Patients have high 30- and 90- day readmission rates, ensuring transition to outpatient care may help avoid readmission.

C. Prognosis and Patient Counseling.

Mortality rates in septic shock are as high as 50%. Long-term consequences range broadly from complete recovery to renal failure, chronic respiratory failure, heart failure as well as neuropsychiatric sequelae, especially resulting from prolonged episodes in intensive care.

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