Sepsis - ClinicalKey

12/6/24, 10:12 p.m.
Sepsis - ClinicalKey
CLINICAL OVERVIEW
Sepsis
Elsevier Point of Care (see details)
Updated December , . Copyright Elsevier BV. All rights reserved.
Synopsis
Urgent Action
Initial treatment needs to proceed rapidly (within hour), regardless of setting. Focus
on immediate stabilization, uid resuscitation, initiation of antimicrobials,
hemodynamic support, and source control
In septic shock, risk of death increases every hour that appropriate antimicrobial
medications are delayed; it is imperative to start treatment on recognition
Early lactate measurement is key to recognizing sepsis; delay is associated with

increased mortality
Surviving Sepsis Campaign bundle ( ) recommends doing the following within the
rst hour when diagnosis is suspected:
Measure lactate level
Obtain blood specimens for culture
Administer broad-spectrum antibiotics
For patients with hypotension or lactate levels of mmol/L or higher
Administer isotonic crystalloid uids; goal is mL/kg
https://www-clinicalkey-com.pucdechile.idm.oclc.org/#!/content/clinical_overview/67-s2.0-dc9afb78-90f7-4c88-bddd-3ed70b7d06f5 1/55
12/6/24, 10:12 p.m. Sepsis - ClinicalKey
If hypotension occurs or persists during or a er uid resuscitation, add

vasopressors
Key Points
Sepsis is a life-threatening systemic syndrome caused by a microbial infection and
dysregulated physiologic response
Characterized by cascade e ect of sepsis, including endothelial damage, vascular

permeability, microvascular dysfunction, and coagulopathies, which, if not treated promptly
and adequately, can lead to multiorgan failure and death
Presentation varies depending on source of infection but o en includes fever, tachypnea,

tachycardia, hypotension, and signs of tissue hypoperfusion
Diagnosis is based on history and clinical presentation, together with laboratory test results
providing evidence for an in ammatory process and microbial infection. CBC with di erential
and other cultures are useful in determining the pathogen responsible; imaging may be done
as an adjunct to identify the anatomical site of infection
Treatment includes immediate stabilization, uid resuscitation, collection of blood and other
relevant specimens for culture, and initiation of antimicrobial treatment, hemodynamic
support, and source control; treatment should proceed rapidly (within hour ), regardless of
setting
Complications include ventilator-associated pneumonia; end-organ dysfunction; deep vein

thrombosis; stress ulcers; and physical, cognitive, and emotional disabilities
Prognosis depends on early identi cation and treatment, response to treatment, and severity at
presentation
Severe sepsis has a mortality rate of % to %
Septic shock has a mortality rate of % to %
Pitfalls
Signs and symptoms of sepsis are highly variable, and hypoperfusion may be subtle in healthy
adults; maintain a high degree of suspicion because prompt identi cation and treatment are
crucial to recovery
Presentation of sepsis in older adults is o en di erent from presentation in younger people,

which may delay diagnosis and treatment
Be aware of subtle signs of sepsis in older adults, including delirium, urinary incontinence,
weakness, malaise, anorexia, and falls
Older adult patients are less likely to present with fever, tachycardia, and hypoxemia than
younger patients
Terminology
Clinical Clari cation

Sepsis is a life-threatening syndrome of organ dysfunction caused by microbial infection in
conjunction with a dysregulated host response
Characterized by a cascade of endothelial damage, vascular permeability, microvascular

dysfunction, and coagulopathies, which can lead to multiorgan failure and death if not treated
promptly and adequately or if not responsive to treatment
Classi cation
Sepsis
Life-threatening organ dysfunction caused by dysregulated host response to infection
Organ dysfunction is de ned by increase from baseline in SOFA score (Sequential Organ
Failure Assessment; originally the Sepsis-Related Organ Failure Assessment) of or more
Septic shock
Subset of sepsis with profound circulatory and cellular/metabolic dysfunction and with
signi cantly greater mortality risk
De ned as need for administration of vasopressor medication to maintain mean arterial

pressure of at least mm Hg and serum lactate level more than mmol/L in the absence of
hypovolemia
Diagnosis
Clinical Presentation
History
Presentation varies, depending on causative agent and portal of entry
Low threshold of suspicion and early recognition of sepsis are essential for successful
outcomes
Thorough and timely history focuses on symptoms, comorbidities, recent surgery, recent
antibiotic use, presence of medical devices, and travel
Common generalized symptoms of sepsis include:
Fever, chills; rigors may be reported
Confusion, anxiety
Fatigue, malaise
Myalgia
Dyspnea
Nausea and vomiting
Decreased urination
Localizing symptoms may include:
Headache and sti neck when meningitis is the cause of sepsis
Cough and pleuritic chest pain with pneumonia
Abdominal pain with gastrointestinal or genitourinary source
Diarrhea with gastrointestinal luminal infections, such as Clostridioides di cile or

toxigenic Escherichia coli infection
Flank pain and dysuria with kidney infection

Bone or joint pain with osteomyelitis or septic arthritis
Skin or so tissue pain with abscesses, wounds, or other so tissue infections
Older adults may have limited or nonspeci c symptoms (eg, poor oral intake, inanition)
Physical examination
Physical examination focuses on detecting generalized signs of sepsis and determining the
source; a careful and thorough examination may uncover an unexpected site
Generalized evidence of sepsis is highly variable but commonly includes:
Fever (above . °C) or hypothermia (below °C)
Fever is the most common sign of sepsis
Hypotension (systolic blood pressure lower than mm Hg and/or mean arterial pressure
lower than mm Hg)
Presenting sign in % of patients with sepsis
Tachycardia (heart rate greater than beats per minute)
Tachypnea (respiratory rate greater than breaths per minute)
Rigors may be observed
Altered mental status; older patients may present with irritability or agitation
Increased capillary re ll time (longer than seconds)
Mottled skin on inspection; petechiae may be seen with severe thrombocytopenia or

meningococcemia
Diaphoresis; clammy skin
Respiratory, gastrointestinal, and genitourinary systems and skin and so tissue are the most
common sites of infection leading to sepsis; signs speci c to a ected system include:
Respiratory
Cough; production of purulent or foul-smelling sputum may be observed by clinician or

reported by patient
Hemoptysis may be observed by clinician or reported by patient with severe pneumonia,

including tuberculosis
Dullness to percussion may indicate pleural e usion (parapneumonic e usion or

empyema) or consolidation
Rhonchi and/or rales on auscultation
Egophony on auscultation indicates consolidation
Gastrointestinal
Abdominal distention on inspection
Decreased bowel sounds on auscultation owing to ileus
Abdominal pain with guarding on palpation; rigidity and rebound indicate peritonitis
Localization of tenderness may indicate source (eg, right upper quadrant for liver or
gallbladder infection)
Genitourinary
Costovertebral tenderness and suprapubic pain on palpation
Vaginal discharge or bleeding
Skin and so tissue
Wounds, ulcerations, furuncles, or carbuncles on inspection
Surgical incisions and IV sites on currently or recently hospitalized patients
There may be erythema and/or edema on inspection
Drainage may be evident, either spontaneous or expressed
Crepitus or uctuance may be palpable; an indurated tender phlebitic cord may be noted
at site of infected peripheral IV line
Lymphadenopathy may be detected proximal to infection site
Other less common ndings may include:
Meningismus, Kernig sign, or Brudzinski sign in meningitis
Point tenderness over a vertebral body may indicate spinal osteomyelitis and/or epidural
abscess
Warm, swollen joint may be a site of septic arthritis
New heart murmur or change in character of a murmur suggesting endocarditis
Causes and Risk Factors
Causes
Microbial pathogens breach skin and/or mucosal barriers to cause systemic infection
Wide range of microbial pathogens may be implicated, depending on site of primary

infection, community patterns, and host characteristics
Most sepsis cases are caused by bacteria; fungi and viruses are less common causes but are
signi cant causes of sepsis in immunocompromised patients
Gram-positive bacteria are responsible for most cases of septic shock in the acute care
setting, followed by gram-negative and mixed bacterial infections
Candidal species are commonly implicated in patients with neutropenia and in infections
associated with indwelling catheters (eg, bloodstream, urinary) and other devices
In uenza virus may cause sepsis directly or may predispose to secondary bacterial
infection and sepsis
Respiratory, gastrointestinal, and genitourinary systems and skin and so tissue are the
primary sites in most infections leading to sepsis (about %)
Common sources of infections leading to sepsis include:
Respiratory tract infections (account for % of sepsis cases)
Community-acquired pneumonia (Related: Community-Acquired Pneumonia in

Adults)
Streptococcus pneumoniae and Staphylococcus aureus are commonly implicated

in sepsis caused by pneumonia
Either may occur de novo or a er in uenza
Hospital-acquired and ventilator-associated pneumonias (Related: Hospital-

Acquired and Ventilator-Associated Pneumonias)
Commonly associated with antibiotic-resistant pathogens
Genitourinary tract infections (account for % of sepsis cases) (Related: Urinary Tract
Infection in Adults)
Usually gram-negative or enterococcal species
Pyelonephritis
Cystitis
Infections related to indwelling urinary catheters (Related: Catheter-Associated

Urinary Tract Infection)
Antibiotic-resistant organisms are o en implicated in hospital and long-term care

settings
Candidal species are common causes in patients with diabetes and patients who
have received broad-spectrum antibiotics
Obstruction of urine ow owing to impacted kidney stones or prostatic hypertrophy

increases the risk of severe infection
Gastrointestinal tract infections (account for % of sepsis cases): o en polymicrobial,

involving enteric gram-negative bacilli, streptococcal species, and anaerobes
Appendicitis
Cholecystitis, cholangitis; biliary obstruction caused by gallstone impaction

increases the risk of severe infection (Related: Cholangitis)
Bowel infarction or perforation with peritonitis (Related: Acute Mesenteric Ischemia)
Diverticulitis
Pancreatitis may cause sepsis due to infection or may cause an in ammatory

response that mimics sepsis (Related: Acute Pancreatitis)
Skin and so tissue infections (account for % of sepsis cases)
Cellulitis
Usually caused by Staphylococcus aureus or streptococci
Community-acquired MRSA infections are prevalent in many areas
Presentation of MRSA infection is o en characterized by deep red or violaceous

erythema surrounding a necrotic center, resembling a spider bite
Carbuncles
Usually caused by Staphylococcus aureus
Wounds (traumatic or surgical)
Traumatic wounds can be infected with a variety of organisms, depending on the

circumstances
Highly resistant Acinetobacter baumannii infections have been associated with

combat wounds
Surgical wound infections may re ect nature of surgery (eg, colon surgery may be
complicated by infection caused by enteric pathogens) or may be caused by
common skin organisms
Antibiotic resistance is common
Infections related to intravascular access devices
May be isolated to insertion site, but secondary bacteremia is common in sepsis
Usually gram-positive organisms (Staphylococcus aureus, coagulase-negative

staphylococci), but gram-negative bacilli and yeast are also common pathogens
Necrotizing fasciitis (Related: Necrotizing So Tissue Infections)
Group A Streptococcus or synergistic polymicrobial infections are the most

common cause of this unusual life-threatening condition
Less common but important sources of sepsis include:
Bone and joint infections
Osteomyelitis (Related: Osteomyelitis in Adults)
Wide variety of pathogens, depending on cause (hematogenous versus

contiguous focus)
Septic arthritis
Common causes vary with age; overall, Staphylococcus aureus and streptococci
are the most common causes
Central nervous system infections
Meningitis (Related: Bacterial Meningitis in Adults)
Typical pathogens vary by age range; Streptococcus pneumoniae and Neisseria

meningitidis are the most common
Encephalitis (Related: Encephalitis in Adults)
Usually viral; HSV and West Nile virus have been associated with sepsis
Epidural abscess
Uncommon; spinal epidural abscesses are usually secondary to bacteremia,

with Staphylococcus aureus as the most frequent pathogen
Risk factors and/or associations
Age
Older adults are at increased risk for sepsis and sepsis-associated hospitalizations owing to
comorbidities, medical interventions, institutionalization, immunosenescence, functional
disability, and malnutrition
About half of patients with sepsis are aged years or older
Sepsis hospitalization rate increases with age
Younger than years: about per , population
Aged years or older: about per , population
Aged years or older: about per , population
Infants are at increased risk for sepsis
Incidence of sepsis in infants is higher than in overall population and pediatric population
(about per , population)
Associated with prematurity, low birth weight, and maternal group B streptococcal infection
Sex
Males are % to % more likely to develop sepsis than females
Males are more likely to develop sepsis due to respiratory tract infection than females; females
are more likely to develop sepsis due to genitourinary tract infection
Genetics
Interleukin β- homozygosity is associated with increased risk of mortality from sepsis
Genetic variants leading to de ciency of mannose-binding lectin are associated with increased
risk of sepsis, particularly pneumococcal sepsis
Other hypotheses related to genetic predisposition to sepsis have been considered but are as
yet unproven
Ethnicity/race
Black Americans are twice as likely to develop sepsis as White Americans; Black Americans have
a higher case fatality rate than White Americans
Likely caused by interaction between di erences in incidence of chronic comorbidities,

socioeconomic factors, and genetics
Hispanic Americans have a lower incidence of sepsis and a lower case fatality rate than Black
Americans; rates among Hispanic Americans are similar to those among White Americans
Other risk factors/associations

Factors that breach natural barriers to pathogen invasion or compromise immune function
increase the risk of sepsis
Recent surgery or hospitalization
Indwelling urinary catheters
Intravascular access devices
Endotracheal tubes
Malnutrition
Burns and/or trauma
Chronic illness
Cancer
Diabetes
Obesity
Immunosuppression (eg, immunosuppressive medical therapy, HIV infection)
IV drug use
Pregnancy or recent childbirth, miscarriage, or pregnancy termination—particularly if the

following are present:
Immunode ciency
Diabetes or gestational diabetes
Invasive procedures such as cesarean or forceps delivery
Prolonged rupture of membranes
Close contact with people with group A streptococcal infection
Continued vaginal bleeding or discharge with o ensive odor
Diagnostic Procedures
Primary diagnostic tools

Diagnosis is based primarily on history and physical examination, coupled with laboratory
test results providing evidence for an in ammatory process and a microbial infection
Presence of organ dysfunction, integral to the diagnosis of sepsis, can be identi ed as an

increase from baseline of points or more in SOFA score (Sequential Organ Failure
Assessment; originally the Sepsis-Related Organ Failure Assessment)
qSOFA score (Quick Sequential Organ Failure Assessment or Quick Sepsis-Related

Organ Failure Assessment) does not require laboratory testing and is as accurate as the
full tool for patients not in the ICU
Score is more speci c than sensitive: a negative test result does not rule out sepsis and
should not be considered a barrier to further testing and monitoring when diagnosis is
suspected
Initial laboratory tests for all patients include a CBC with di erential; a metabolic panel;
creatinine, bilirubin, and lactate levels; coagulation tests; blood gas levels; and urinalysis
Elements of SOFA score include platelet count, bilirubin level, creatinine level, and PaO₂
(partial pressure of oxygen)
Obtain results promptly; in particular, measure lactate level within hour of

presentation of patient with possible sepsis
For all patients, obtain blood and a specimen from any suspected source of infection for
culture. Do this before initiation of antimicrobial therapy if it can be done without
signi cant delay (less than minutes)
Additional laboratory tests may provide etiologic information (eg, rapid in uenza antigen
testing; , -β-D-glucan assay; legionella and pneumococcal antigens)
Perform imaging (eg, radiography, ultrasonography, CT, MRI) to con rm suspected

anatomical site of infection; speci c choice of imaging mode depends on site of suspected
infection
Measurement of MAP (mean arterial pressure) is indicated for patients with persistent
hypoperfusion a er uid challenge
May provide support for diagnosis of sepsis and forms a baseline to guide uid and
vasopressor treatment
Several serum markers have been suggested as indicators of sepsis (eg, procalcitonin, C-
reactive protein), but their role in both diagnosis and management remains unclear
Laboratory
Imaging
Functional testing
Di erential Diagnosis
Most common
Hypovolemic or hemorrhagic shock
Rapid uid loss resulting in inadequate circulating volume and hypoperfusion; most o en
caused by burns, trauma, gastrointestinal bleeding, or ruptured abdominal aortic aneurysm
Similar features: tachypnea, tachycardia, malaise, hypotension, hypoxia, decreased capillary

re ll, mottled skin, oliguria, pallor, and altered mental status
Di erentiating features: absence of fever; abnormalities in WBC count are usually absent or
minimal
Diagnosed by history, physical examination, and imaging that indicate source of

hemorrhage or other volume loss
Pulmonary embolism (Related: Pulmonary Embolism)
Sudden occlusion of a pulmonary artery, most o en caused by a dislodged thrombus
Similar features: dyspnea, tachypnea, hypoxia
Di erentiating features: onset of symptoms is abrupt; pleuritic chest pain is common
Diagnosed by multidetector-row CT angiography or CT pulmonary angiography, which

detects pulmonary emboli; D-dimer levels are usually elevated
Myocardial infarction (Related: Acute Coronary Syndromes)
Myocardial necrosis resulting from occlusion of a coronary artery
Similar features: dyspnea, fatigue
Di erentiating features: retrosternal chest pain and/or pressure radiating to neck, jaw,
shoulder, and/or arm
Diagnosed by ST elevation, ST depression, or T-wave inversion on ECG; cardiac troponin

level is elevated
Acute pancreatitis (Related: Acute Pancreatitis)
Sudden onset of parenchymal and pancreatic fat necrosis with in ammation of pancreas
Similar features: fever, diaphoresis, nausea, vomiting
Di erentiating features: sudden onset of constant epigastric or le upper quadrant pain that
may radiate to the back, chest, or anks
Diagnosed by serum amylase and lipase levels more than times the upper reference limit,
with con rmatory ndings from abdominal imaging
Diabetic ketoacidosis (Related: Diabetic Ketoacidosis)
Decompensated state of diabetes that presents with the biochemical triad of hyperglycemia,
ketonemia, and metabolic acidosis
Similar features: tachycardia, hypotension, weakness, nausea, vomiting
Di erentiating features: polyuria, polydipsia, polyphagia, absence of fever, Kussmaul

respirations, acetone breath
Diagnosed by hyperglycemia, positive urine and serum ketones, decreased arterial pH,
elevated anion gap, and decreased serum bicarbonate level
Adrenal insu ciency (Related: Primary Adrenal Insu ciency)
Cortisol and mineralocorticoid de ciency in primary adrenal insu ciency, or suppression

of hypothalamic-pituitary axis in secondary adrenal insu ciency
Similar features: tachycardia, weakness, vomiting, hypotension, altered mental status
Di erentiating features: increased skin pigmentation, salt craving, weight loss, more gradual
progression of symptoms
Diagnosed by decreased serum cortisol level and elevated adrenocorticotropic hormone

level
Transfusion reaction
Adverse reaction to blood or blood product transfusion
Similar features: fever, rigors, dyspnea
Di erentiating features: pruritus, urticaria, angioedema, evidence of hemolysis
Diagnosed by history of blood transfusion and analysis of pretransfusion and

posttransfusion blood samples
Treatment
Goals
Initial respiratory and hemodynamic stabilization to promote perfusion and maintain vital
organ function
Within the rst hour that diagnosis is suspected
Begin uid resuscitation for patients who are hypotensive or who have serum lactate
levels of mmol/L or higher; complete within hours a er presentation
If hypotension persists during or a er uid resuscitation, start vasopressors immediately
Initial antimicrobial treatment: broad-spectrum agents until underlying infection is identi ed;
tailored antimicrobial treatment once causative pathogen is identi ed
Within the rst hour that diagnosis is suspected, begin empiric therapy
Source control within the rst hours, if possible
Prevention of complications and sequelae
Disposition
Admission criteria
Sepsis requires inpatient acute care for monitoring, IV antimicrobial therapy, and supportive care
Criteria for ICU admission

Septic shock with hemodynamic instability requires ICU admission for hemodynamic
monitoring and treatment
Recommendations for specialist referral

Refer to an infectious disease specialist to identify cause and direct appropriate antimicrobial
therapy
Consult a clinical pharmacologist to optimize dosing regimen
Refer to critical care specialists to guide resuscitative e orts in septic shock
Additional specialist referral depends on cause of sepsis and/or organ dysfunction resulting
from sepsis; may include cardiologist, pulmonologist, nephrologist, or gastroenterologist
Surgical referral may be required for source control of abdominal or necrotizing infections
Treatment Options
Initial treatment o en occurs in the emergency department and is continued in the inpatient
setting; treatment should proceed rapidly regardless of setting
Implementation of multidisciplinary sepsis bundles that promote early identi cation and
provide management protocols may result in improved outcomes
Treatment includes immediate stabilization, uid resuscitation, initiation of antimicrobials,

hemodynamic support, and source control
Ensure patency of airway and provide supplemental oxygen; support ventilation mechanically
if necessary to improve oxygenation, protect airway, or prevent imminent respiratory failure
Invasive monitoring of hemodynamic parameters is recommended for patients with septic

shock, and it can be used for patients without shock to monitor response to uids
Intra-arterial blood pressure monitoring is recommended for patients with sepsis who are
not responsive to initial uid therapy or who require vasopressor treatment
Establish adequate IV access ( large-gauge IV devices, preferably gauge or larger) and begin
infusing crystalloid solution immediately on suspicion of sepsis and either hypotension or a
lactate level of mmol/L or higher; the recommended goal is mL/kg within hours
Early goal-directed therapy, a core component of previous sepsis guidelines, has not been
shown to reduce mortality in more recent studies
Nevertheless, adequate uid resuscitation is essential, and many patients require large
volumes, depending on hemodynamic response
Normalization of lactate levels may also be used as a guide to adequate uid resuscitation
Bedside cardiac ultrasonography and other techniques may be used to assess initial uid
responsiveness; serial follow-up studies may help to determine uid repletion and
indication for inotropic therapy
Evidence and guidelines suggest that crystalloids should be used as rst line uid therapy;
albumin may be needed for patients requiring large volumes of crystalloids
Normal saline has typically been the primary IV uid given; however, balanced crystalloid
solutions (eg, lactated Ringer solution) are now recommended because they may have fewer
adverse metabolic e ects and a lower rate of complications
A er collecting blood and other specimens for culture, but within the rst hour of
recognizing septic shock or a high likelihood of sepsis, begin antimicrobial therapy
Immediate (within hour) administration of antibiotics may reduce mortality by as much as

% compared with later administration
Most recent Surviving Sepsis guidelines recommend antibiotic administration within

hour for adult patients with possible septic shock or a high likelihood of sepsis
For adult patients with possible sepsis without shock, the recommendation is to quickly
assess for infection and administer antibiotics within hours if sepsis is still suspected
Infectious Diseases Society of America does not endorse recommending a rigid -hour time
frame; instead, they recommend prompt administration of antibiotics once the presumptive
diagnosis is made
International guidelines for children recommend starting antibiotic therapy as soon as

possible a er appropriate evaluation and:
Within hour of recognition for those with septic shock
Within hours of recognition for those with sepsis-associated organ dysfunction but
without shock
Initial antimicrobial therapy is empiric
Begin with IV anti-infective agents that are active against all likely pathogens (ie, bacterial,
viral, fungal)
Choice of speci c agent or agents for empiric antimicrobial therapy depends on

suspected source of infection, clinical situation, recent antibiotic use, and local resistance
patterns
Current Surviving Sepsis guideline recommends empiric combination therapy using at

least antibiotics from di erent classes for patients with septic shock
Consult a clinical pharmacist if possible to optimize dosing and administration according

to pharmacokinetic and pharmacodynamic principles (eg, continuous versus intermittent
infusion of β-lactam agents)
While continuous infusion has advantage of delivering constant drug levels above the
minimal inhibitory concentration, a randomized trial comparing meropenem given as
a continuous or intermittent infusion showed no signi cant di erence in mortality or
length of stay
Optimize antibiotic therapy once culture and sensitivity results are available; this may
involve broadening or narrowing coverage, or stopping antibiotic if sepsis is excluded
For suspected pneumonia
Community-acquired pneumonia
Broad-spectrum β-lactam agent (cefotaxime, ce azidime, cefepime, or piperacillin-

tazobactam) plus either a respiratory uoroquinolone (moxi oxacin or levo oxacin) or
azithromycin
Medical care–associated pneumonia
Antipseudomonal carbapenem (imipenem, doripenem, or meropenem) or cefepime
If legionella is a possibility, add azithromycin or a uoroquinolone
For either community-acquired or medical care–associated pneumonia, add oseltamivir if

in uenza is suspected or con rmed; IV peramivir can be used if oral or enteric
oseltamivir cannot be tolerated
For suspected abdominal source
Community-acquired infection
Carbapenem (imipenem, doripenem, or meropenem) or piperacillin-tazobactam with

or without an aminoglycoside
For suspected biliary tract infection, piperacillin-tazobactam or ampicillin-sulbactam

or ce riaxone plus metronidazole
Medical care–associated infection
Antipseudomonal carbapenem (imipenem or meropenem) with or without an

aminoglycoside
For suspected urinary source
Antipseudomonal uoroquinolone (cipro oxacin or levo oxacin)
If urine Gram stain shows gram-positive cocci, use either ampicillin or vancomycin,
with or without an aminoglycoside
Vancomycin plus either imipenem or meropenem or cefepime
For suspected skin and so tissue infection
Vancomycin or daptomycin plus either imipenem or meropenem or piperacillin-

tazobactam
Vancomycin or daptomycin plus either imipenem or meropenem or cefepime
For either community-acquired or medical care–associated infection
Add clindamycin if toxin-producing organism is suspected (eg, Streptococcus

pyogenes, Staphylococcus aureus)
For unknown source in adults
Vancomycin plus a carbapenem (imipenem, doripenem, meropenem, or ertapenem)
Vancomycin plus cefepime
For unknown source in children
Third-generation cephalosporin (ce riaxone or cefotaxime) plus vancomycin
Vancomycin plus either piperacillin-tazobactam, ce azidime, cefepime, or a

carbapenem (imipenem or meropenem)
Other considerations
Add oseltamivir if in uenza is likely
There are insu cient data about e cacy of zanamivir, IV peramivir, and oral baloxavir
in hospitalized patients with in uenza; however, can use IV peramivir if patient cannot
tolerate oral or enteric oseltamivir
An echinocandin may be added for medical care–associated cases in which yeast is a

possible pathogen (eg, cases involving indwelling vascular catheters, intra-abdominal
infection, or neutropenia)
Add daxomicin, or oral or enteral vancomycin (with or without IV metronidazole) if

Clostridioides di cile infection is a possibility
Provide vasopressor agents to target an MAP (mean arterial pressure) of at least mm Hg, if
initial uid resuscitation has not achieved that goal; a higher target (eg, mm Hg or more)
may be appropriate for patients with baseline hypertension
Higher MAP target of to mm Hg resulted in no di erence in mortality or need for

renal replacement therapy in patients with shock requiring vasoactive medications; in the
subgroup of patients with history of chronic hypertension, targeting a higher MAP reduced
risk for renal replacement therapy
Norepinephrine is rst line therapy
There is some evidence that early administration (within hours of shock onset) of
norepinephrine improves outcomes and that every hour of delay results in an
incremental increase in mortality
Epinephrine and vasopressin may be added if necessary to achieve target MAP
Vasopressin is the preferred second line agent
Dopamine is a third line agent used only for patients meeting speci c cardiac criteria
Vasopressor use requires balancing the risks of hypotension against vasopressor-associated

complications; some evidence suggests lower vasopressor exposure is associated with
reduced mortality
Consider inotropic therapy with dobutamine as an adjunct or alternative to vasopressor

therapy in selected patients with elevated cardiac lling pressures and low cardiac output
suggestive of myocardial dysfunction or persistent clinical signs of hypoperfusion a er
adequate volume and MAP have been achieved
Consider corticosteroid therapy with IV hydrocortisone if uid resuscitation and vasopressor

therapy do not restore hemodynamic stability
A meta-analysis showed that systemic corticosteroids hasten resolution of shock
A Cochrane review indicates treatment with corticosteroids results in large reductions in

length of hospitalization and probably reduces mortality among adults and children with
sepsis
Source control within the rst hours if possible (eg, drainage of abscess, debridement of
necrotic tissue, relief of ureteral obstruction, removal of infected device)
Additional treatment required a er initial management in select cases of sepsis
Blood product administration
RBC transfusion if hemoglobin level is less than g/dL a er tissue hypoperfusion has been
treated adequately
Evidence suggests that transfusion to higher levels does not confer an advantage in terms
of mortality or ischemic events
Acute hemorrhage, myocardial ischemia, or severe hypoxemia may necessitate a higher

transfusion threshold
Administer platelets prophylactically to patients with sepsis, thrombocytopenia, and

increased risk for bleeding
Less than , cells/mm³
Less than , cells/mm³ if there is a signi cant risk of bleeding
Less than , cells/mm³ for active bleeding, invasive procedure
Glycemic control targeting an upper blood glucose level of mg/dL or less
Evidence suggests that there is no bene t in tighter control and that adverse events are more
frequent
Deep vein thrombosis prophylaxis using a combination of daily pharmacologic therapy and
intermittent pneumatic compression devices
Stress ulcer prophylaxis with a proton pump inhibitor or histamine type- blocker is
recommended for patients with sepsis or septic shock who are at risk for gastrointestinal
bleeding
Continuous renal replacement therapy or intermittent hemodialysis is recommended for acute

kidney injury
Oral nutrition or (if necessary) enteral nutrition within the rst hours a er diagnosis, with
low-dose feeding as tolerated
If enteral feeding is not possible initially, a -day trial of IV glucose and advancement of
enteral feeding is recommended over early parenteral nutrition
Once the causative pathogen is identi ed, de-escalate antimicrobial treatment, based on culture
and sensitivity results, and continue for a duration appropriate to the diagnosis ( - days in
most cases)
Combination therapy is recommended in some circumstances, which are as follows:
Ongoing septic shock
Infection with certain multidrug-resistant pathogens such as Acinetobacter and

Pseudomonas species
Bacteremic infections caused by Streptococcus pneumoniae (eg, β-lactam agent plus a

macrolide)
Group A streptococcal toxic shock (penicillin and clindamycin)
Shorter courses may be appropriate for patients with urinary tract or intra-abdominal
infections and rapid clinical response to prompt source control
De-escalation may be associated with improved survival
Procalcitonin levels within reference range can be used to support a decision to discontinue
antibiotics for these patients and those who initially appeared septic but in whom no evidence
of infection has emerged
Procalcitonin-guided antibiotic therapy results in shorter duration of treatment and

reduced long-term infection-associated adverse events (eg, Clostridioides di cile infection)
but no greater risk of treatment failure
Antimicrobial therapy may need to be continued beyond to days in certain clinical

situations
Endocarditis
Immunologic de ciencies (eg, neutropenia)
Slow clinical response to antimicrobial therapy
Undrainable foci of infection
Bacteremia with Staphylococcus aureus
Select fungal and viral infections
Drug therapy
Antimicrobial agents
Broad-spectrum penicillins
Ampicillin-sulbactam
Ampicillin Sodium, Sulbactam Sodium Solution for injection; Infants, Children, and
Adolescents: to mg/kg/day ampicillin component ( to mg/kg/day
ampicillin; sulbactam) IV divided every hours (Max: g/day ampicillin [ g/day
ampicillin; sulbactam]); doses up to mg/kg/day ampicillin component (
mg/kg/day ampicillin; sulbactam) have been reported for serious infections.
Ampicillin Sodium, Sulbactam Sodium Solution for injection; Adults: g( g

ampicillin and g sulbactam) IV every hours.
Piperacillin-tazobactam
Piperacillin Sodium, Tazobactam Sodium Solution for injection; Infants, Children, and
Adolescents: mg/kg/dose piperacillin component ( mg/kg/dose piperacillin;
tazobactam) IV every hours (Max: g/dose piperacillin [ . g/dose piperacillin;
tazobactam]).
Piperacillin Sodium, Tazobactam Sodium Solution for injection; Adults: . g ( g

piperacillin and . g tazobactam) IV every hours.
Cephalosporins
Third generation
Ce riaxone
Ce riaxone Sodium Solution for injection; Infants, Children, and Adolescents:

mg/kg/dose (Max: g/dose) IV every hours.
Ce riaxone Sodium Solution for injection; Adults: to g IV every to hours.
Ce azidime
Antipseudomonal cephalosporin
Ce azidime Sodium Solution for injection; Infants and Children: to

mg/kg/day (Max: g/day) IV divided every hours; to mg/kg/day (Max:
g/day) IV divided every hours for serious P. aeruginosa infections.
Ce azidime Sodium Solution for injection; Adolescents: g IV every hours.
Ce azidime Sodium Solution for injection; Adults: g IV every hours.
Fourth generation
Cefepime
Cefepime Hydrochloride Solution for injection; Infants, Children, and Adolescents:

Cefepime Hydrochloride Solution for injection; Adults: g IV every hours.
Carbapenems
Imipenem-cilastatin
Imipenem, Cilastatin Sodium Solution for injection; Infants to months:

mg/kg/dose IV every hours.
Imipenem, Cilastatin Sodium Solution for injection; Infants, Children, and

Adolescents months to years: to mg/kg/dose IV every hours (Max: g/day).
Imipenem, Cilastatin Sodium Solution for injection; Adults: mg IV every hours

or g IV every hours.
Meropenem
Meropenem Solution for injection; Infants, Children, and Adolescents: to

Meropenem Solution for injection; Adults: g IV every hours.
Levo oxacin
Provides coverage of respiratory pathogens and gram-negative aerobic bacteria, including

Pseudomonas aeruginosa
Levo oxacin, Dextrose Solution for injection; Adults: mg IV every hours.
Azithromycin
Azithromycin Solution for injection; Infants, Children, and Adolescents months to

years†: mg/kg/dose (Max: mg/dose) IV once daily for days, followed by oral
therapy to complete a -day treatment course.
Azithromycin Solution for injection; Adolescents to years: mg IV once daily for

at least days, followed by oral therapy to complete a -day treatment course.
Azithromycin Solution for injection; Adults: mg IV once daily for at least days.
Aminoglycosides
Amikacin (extended-interval dosing)
Enhanced antipseudomonal activity
Amikacin Sulfate Solution for injection; Infants, Children, and Adolescents: to .

mg/kg/dose IV/IM every hours.
Amikacin Sulfate Solution for injection; Adults: to mg/kg/dose IV/IM every

hours.
Gentamicin (extended-interval dosing)
Gentamicin Sulfate Solution for injection; Infants, Children, and Adolescents: to .

mg/kg/dose IV/IM every hours.
Gentamicin Sulfate Solution for injection; Adults: to mg/kg/dose IV/IM every

hours.
Vancomycin
Oral
For Clostridioides di cile infection
For initial episode
Vancomycin Hydrochloride Oral solution; Infants, Children, and Adolescents:

mg/kg/dose (Max: mg/dose) PO times daily for days.
Vancomycin Hydrochloride Oral capsule; Adults: mg PO times daily for

days.
For fulminant infection
Vancomycin Hydrochloride Oral solution; Infants, Children, and Adolescents:

mg/kg/dose (Max: mg/dose) PO times daily for days; consider adding
metronidazole IV.
Vancomycin Hydrochloride Oral capsule; Adults: mg PO or via nasogastric

tube times daily with IV metronidazole. If clinical improvement a er to
hours, consider decreasing the dose to mg PO every hours for days. If an
ileus is present, consider adding vancomycin as a retention enema.
IV
Vancomycin Hydrochloride Solution for injection; Infants to months: to

mg/kg/day IV divided every to hours; adjust dose based on target PK/PD parameter.
Consider loading dose of to mg/kg IV.
Vancomycin Hydrochloride Solution for injection; Infants and Children months to

years: to mg/kg/day IV divided every hours (Usual Max: , mg/day; may
require up to , mg/day); adjust dose based on target PK/PD parameter. Consider
loading dose of to mg/kg IV.
Vancomycin Hydrochloride Solution for injection; Obese Infants and Children

months to years: mg/kg/dose (Max: , mg/dose) IV loading dose, followed by
to mg/kg/day IV divided every hours (Usual Max: , mg/day; may require up
to , mg/day); adjust dose based on target PK/PD parameter.
Vancomycin Hydrochloride Solution for injection; Children and Adolescents to

years: to mg/kg/day IV divided every to hours (Usual Max: , mg/day; may
require up to , mg/day); adjust dose based on target PK/PD parameter. Consider
loading dose of to mg/kg (Max: , mg/dose) IV.
Vancomycin Hydrochloride Solution for injection; Obese Children and Adolescents

to years: mg/kg/dose (Max: , mg/dose) IV loading dose, followed by to
mg/kg/day IV divided every to hours (Usual Max: , mg/day; may require up to
, mg/day); adjust dose based on target PK/PD parameter.
Vancomycin Hydrochloride Solution for injection; Adults: to mg/kg/dose (Max:

, mg/dose) IV loading dose, followed by to mg/kg/dose IV every to hours;
adjust dose based on target PK/PD parameter.
Vancomycin Hydrochloride Solution for injection; Obese Adults: to mg/kg/dose

(Max: , mg/dose) IV loading dose, followed by to mg/kg/dose IV every to
hours (Usual Max: , mg/day); adjust dose based on target PK/PD parameter.
Fidaxomicin
For Clostridioides di cile infection
Fidaxomicin Oral suspension; Infants months and older weighing to kg: mg

PO twice daily for days.
Fidaxomicin Oral suspension; Infants and Children months and older weighing to
kg: mg PO twice daily for days.
Fidaxomicin Oral suspension; Infants and Children months and older weighing to
. kg: mg PO twice daily for days.
Fidaxomicin Oral suspension; Children and Adolescents weighing . kg or more:

mg PO twice daily for days.
Fidaxomicin Oral tablet; Adults: mg PO twice daily for days.
Metronidazole
Oral
For nonsevere initial Clostridioides di cile infection
Metronidazole Oral suspension; Infants, Children, and Adolescents: . mg/kg/dose

(Max: mg/dose) PO every to hours for days.
Metronidazole Oral tablet; Adults: mg PO times daily for days.
IV
For general sepsis
Metronidazole Solution for injection; Infants, Children, and Adolescents: . to

mg/kg/day (Max: . g/day) IV divided every hours.
Metronidazole Solution for injection; Adults: mg IV every to hours.
For fulminant initial Clostridioides di cile infection
Metronidazole Solution for injection; Infants, Children, and Adolescents: .

mg/kg/dose (Max: mg/dose) IV every to hours for days plus vancomycin.
Metronidazole Solution for injection; Adults: mg IV every hours plus

vancomycin.
Clindamycin
Clindamycin Solution for injection; Infants, Children, and Adolescents month to

years: mg/kg/day (Max: , mg/day) IV divided every to hours.
Clindamycin Solution for injection; Adolescents years: to mg IV every hours;

doses up to , mg/day IV have been used for life-threatening infections in adults.
Clindamycin Solution for injection; Adults: to mg IV every hours; doses up to

, mg/day IV have been used for life-threatening infections.
Antiviral agents
Oseltamivir
Oseltamivir Phosphate Oral suspension; Infants to months: mg/kg/dose PO twice

daily for days.
Oseltamivir Phosphate Oral suspension; Infants to months: . mg/kg/dose PO

twice daily for days.
Oseltamivir Phosphate Oral suspension; Children weighing kg or less: mg PO

Oseltamivir Phosphate Oral suspension; Children weighing to kg: mg PO

Oseltamivir Phosphate Oral suspension; Children weighing to kg: mg PO

Oseltamivir Phosphate Oral suspension; Children and Adolescents weighing more than
kg: mg PO twice daily for days.
Oseltamivir Phosphate Oral capsule; Adults: mg PO twice daily for days.
Peramivir
Peramivir Solution for injection; Infants and Children months to years:

mg/kg/dose (Max: mg/dose) IV as a single dose.
Peramivir Solution for injection; Adolescents: mg IV as a single dose.
Peramivir Solution for injection; Adults: mg IV as a single dose.
Antifungal agents
Caspofungin
Caspofungin Solution for injection; Infants to months†: Very limited data available.
mg/m /dose IV once daily may provide comparable exposure to usual dose in adults.
Treat for weeks a er documented clearance from the bloodstream and resolution of
signs and symptoms for invasive candidiasis without metastatic complications.
Coadministration of certain drugs may need to be avoided or dosage adjustments may
be necessary; review drug interactions.
Caspofungin Solution for injection; Infants, Children, and Adolescents months to

years: mg/m /dose (Max: mg/dose) IV loading dose on day , followed by
mg/m /dose (Max: mg/dose) IV once daily. Treat for weeks a er documented
clearance from the bloodstream and resolution of signs and symptoms for invasive
candidiasis without metastatic complications. May increase dose to mg/m /dose
(Max: mg/dose) if there is an inadequate clinical response. Coadministration of
certain drugs may need to be avoided or dosage adjustments may be necessary; review
drug interactions.
Caspofungin Solution for injection; Adults: mg IV loading dose on day , then

mg IV once daily. Treat for weeks a er documented clearance from the bloodstream
and resolution of signs and symptoms for invasive candidiasis without metastatic
complications. Coadministration of certain drugs may need to be avoided or dosage
adjustments may be necessary; review drug interactions.
Vasopressors
Norepinephrine
First line therapy
Norepinephrine Bitartrate Solution for injection; Infants†, Children†, and Adolescents†:

. mcg/kg/minute continuous IV infusion; titrate to clinical response (Usual Max:
mcg/kg/minute).
Norepinephrine Bitartrate Solution for injection; Adults: . mcg/kg/minute (weight-

based) or to mcg/minute ( at-dose) continuous IV infusion, initially. Titrate by .
mcg/kg/minute (or more in emergency cases) to clinical response. Usual dosage range:
. to . mcg/kg/minute (weight-based) or to mcg/minute ( at-dose). Infusion rates
up to . mcg/kg/minute have been used.
Epinephrine
May be added to norepinephrine or used as an alternative where norepinephrine is

unavailable
Epinephrine Hydrochloride Solution for injection; Infants†, Children†, and Adolescents†:

. to mcg/kg/minute continuous IV infusion. Titrate to clinical response.
Epinephrine Hydrochloride Solution for injection; Adults: . to mcg/kg/minute

continuous IV infusion. Titrate by . to . mcg/kg/minute every to minutes to
clinical response.
Vasopressin

unavailable
Vasopressin Solution for injection; Infants†, Children†, and Adolescents†: . to

milliunits/kg/minute continuous IV infusion; reserve for catecholamine-resistant shock,
dosage range not well established.
Vasopressin Solution for injection; Adults: . unit/minute continuous IV infusion,

initially; titrate by . unit/minute every to minutes to clinical response. Max: .
unit/minute.
Dopamine

unavailable
Dopamine Hydrochloride Solution for injection; Infants†, Children†, and Adolescents†:

to mcg/kg/minute continuous IV infusion, initially. Titrate by . to mcg/kg/minute
until desired hemodynamic response is attained. Usual Max: to mcg/kg/minute.
Dopamine Hydrochloride Solution for injection; Adults: to mcg/kg/minute

continuous IV infusion, initially. Titrate by to mcg/kg/minute until desired
hemodynamic and/or renal response is attained. Usual dosage: to mcg/kg/minute.
Max: mcg/kg/minute.
Inotropes
Dobutamine
May be considered as an adjunct or alternative to vasopressor therapy in select cases
Elevated cardiac lling pressures and low cardiac output suggestive of myocardial
dysfunction
Persistent clinical signs of hypoperfusion a er adequate volume and MAP have been
achieved
Dobutamine Hydrochloride Solution for injection; Infants, Children, and Adolescents: .

to mcg/kg/minute continuous IV/IO infusion. Titrate every few minutes to clinical
response. Usual dose: to mcg/kg/minute.
Dobutamine Hydrochloride Solution for injection; Adults: . to mcg/kg/minute

continuous IV infusion. Titrate every few minutes to clinical response. Usual dose: to
mcg/kg/minute. Max: mcg/kg/minute.
Corticosteroids
Hydrocortisone
Continuous IV hydrocortisone if uid resuscitation and vasopressor therapy do not

restore hemodynamic stability
Hydrocortisone Sodium Succinate Solution for injection; Infants and Children month
to years: mg/kg [weight-based], mg [ at-dose], or mg/m [BSA-based] IV bolus,
followed by to mg/kg/day [weight-based] or to mg/m /day [BSA-based] IV in
divided doses at -hour intervals or as a continuous IV infusion.
Hydrocortisone Sodium Succinate Solution for injection; Children to years: mg/kg

(Max: mg) [weight-based], mg [ at-dose], or mg/m [BSA-based] IV bolus,
followed by to mg/kg/day [weight-based] or to mg/m /day [BSA-based] IV in
divided doses at -hour intervals or as a continuous IV infusion.
Hydrocortisone Sodium Succinate Solution for injection; Adolescents: mg/kg (Max:

mg) [weight-based], mg [ at-dose], or mg/m [BSA-based] IV bolus, followed by
to mg/kg/day [weight-based] or to mg/m /day [BSA-based] IV in divided doses at
-hour intervals or as a continuous IV infusion.
Hydrocortisone Sodium Succinate Solution for injection; Adults: mg IV every hours

or mg/day continuous IV infusion.
Nondrug and supportive care
Procedures
Fluid resuscitation
Begin uid resuscitation with an infusion of isotonic crystalloid solution within the rst
hour to patients with hypotension or a lactate level of mmol/L; the recommended goal is
mL/kg within hours
Guidelines recommend use of a balanced solution (eg, lactated Ringer solution,

Hartmann solution) over normal saline
Albumin may be needed in patients requiring large volumes of crystalloids
Take care not to administer too much uid, especially if there is little hemodynamic
response to initial uids
Titrate initial and continued uid administration based on physiologic parameters such as
heart rate, blood pressure, respiratory rate, oxygen saturation, urine output, and (if invasive
monitoring has been started) MAP (goal is mm Hg for most patients, including children
older than years )
Such clinical monitoring may be supplemented by bedside cardiac ultrasonography if

available
As patient's condition improves, de-escalate uid therapy and/or adopt uid removal
strategies
May use normalization of lactate levels as a guide, in addition to hemodynamic parameters
A er hemodynamic stabilization, a restrictive approach to IV uid administration

(prioritizing vasopressors and lower IV uid volumes) has been associated with a reduced
duration of mechanical ventilation and ICU stay when compared with a more liberal
approach (prioritizing higher volumes of IV uids before vasopressor use)
However, -day mortality was not signi cantly di erent between patients with sepsis-
induced hypotension refractory to initial uid resuscitation who were treated with uid
restriction and early initiation of vasopressors compared with more liberal uid
administration
Respiratory support
Give supplemental oxygen initially to all adult patients with sepsis to achieve target oxygen
saturation of % to %
More intensive respiratory support is required if supplemental oxygen does not improve
oxygenation
For patients with severe hypoxia, increased ventilatory support may include noninvasive
ventilation or high- ow oxygen via nasal canula (preferred)
If necessary, use mechanical ventilation for sepsis-induced acute respiratory distress

syndrome
May be needed to improve oxygenation, protect airway, or prevent imminent respiratory

failure
Target a tidal volume of mL/kg of predicted body weight
Target a plateau pressure of cm H₂O or less
Apply positive end-expiratory pressure to avoid alveolar collapse at end expiration
Use strategies of higher rather than lower levels of positive end-expiratory pressure with
moderate to severe acute respiratory distress syndrome
Implement recruitment maneuvers with severe refractory hypoxemia (eg, CPAP), if

needed
Consider prone positioning in patients with a PaO₂/FiO₂ ratio of mm Hg or less
Risk reduction strategies to prevent development of ventilator-associated pneumonia

include:
Elevate head of bed to ° to °
Selective oral and digestive decontamination
Oral care with toothbrushing (without chlorhexidine)
Establish weaning protocols for patients to undergo spontaneous breathing trials

regularly to evaluate whether mechanical ventilation can be discontinued
Use caution with sedation, analgesia, and neuromuscular blockade for mechanically
ventilated patients
Minimize continuous or intermittent sedation in mechanically ventilated patients
Avoid neuromuscular blockade in patients without sepsis-induced acute respiratory

distress syndrome
Use a short course of neuromuscular blockade of no longer than hours for patients
with early sepsis-induced acute respiratory distress syndrome and a PaO₂/FiO₂ ratio less
than mm Hg
Source control
Determine source of infection as quickly as possible, and begin intervention within hours
if possible
Use the least invasive but adequately e ective strategy for source control (eg, percutaneous
versus open surgical technique)
Depending on the source, strategies may include the following:
Drain abscess
Debride infected tissue and necrotic tissue
Remove infected device
Remove intravascular catheters that are suspected to be a source as soon as alternate

access is established
Blood product administration
Blood products may be required a er initial management in select cases
Transfuse RBCs if:
Hemoglobin level is less than g/dL a er tissue hypoperfusion has been treated
adequately
Target hemoglobin level a er transfusion is to g/dL for adults
Transfusion may be indicated at higher thresholds for patients with myocardial

ischemia, hemorrhage, or severe hypoxemia
Administer platelets prophylactically if platelet count is:
, cells/mm³ or lower in the absence of bleeding
, cells/mm³ or lower with a signi cant risk of bleeding
, cells/mm³ or lower for active bleeding, surgery, or invasive procedures
Glycemic control
Target an upper blood glucose level of mg/dL or less in adults and children
Begin insulin dosing when consecutive blood glucose level readings are higher than
mg/dL
Adjust insulin dose based on repeated blood glucose level measurements every to hours
until glucose values and insulin rates are stable, then monitor every hours and adjust
insulin dose as needed
Deep vein thrombosis prophylaxis
Subcutaneous low-molecular-weight heparin daily is the recommended pharmacologic

therapy
For creatinine clearance less than mL/minute, use an alternate anticoagulant with lower
renal clearance (eg, unfractionated heparin) or dose-adjusted low-molecular-weight heparin
For patients with a contraindication for pharmacoprophylaxis, mechanical prophylactic

treatment is recommended
Combination of daily pharmacologic therapy and intermittent pneumatic compression

devices may be used for patients who have no contraindications for either measure
Stress ulcer prophylaxis
Recommended for patients at risk for bleeding, such as those with the following:
Thrombocytopenia
Multiorgan failure
Mechanical ventilation
Proton pump inhibitors have been shown to signi cantly decrease clinically signi cant
stress-related mucosal bleeding compared with histamine type- blockers
Renal replacement therapy
For patients with acute kidney failure resulting from sepsis
Continuous renal replacement therapies and intermittent hemodialysis are equivalent for
most patients
Use continuous therapies to facilitate management of uid balance in hemodynamically

unstable septic patients
Nutrition
Administer oral feedings or (if necessary) enteral feedings within the rst hours a er
diagnosis
Avoid mandatory full caloric feeding in the rst week
Advance low-dose feeding only as tolerated
Avoid parenteral nutrition in the rst week, even if enteral feeding is not possible initially;
use IV glucose and attempt to advance enteral feeding
Consider prokinetic agents for patients with feeding intolerance
Consider use of a postpyloric feeding tube for patients with feeding intolerance who are at
risk for aspiration
Use nutrition without speci c immunomodulating supplementation
Comorbidities
Common comorbidities include conditions that cause immunosuppression:
HIV infection
Hematologic malignancies
Splenic de ciency
Chronic conditions requiring high-dose corticosteroids or other immunosuppressant

therapy
Chronic kidney failure
Diabetes mellitus
Excessive alcohol use
Special populations
Older adult patients
More likely to have repeated antimicrobial exposure owing to chronic illness and medical
intervention, resulting in multidrug-resistant microbial ora; very-broad-spectrum
empirical antimicrobial therapy is required
Age-related renal and hepatic impairment put older adult patients at higher risk for adverse
events related to drug therapy; careful drug monitoring is required, and dose adjustment
may be necessary
Increased capacitance of vasculature in older adult patients creates a narrower therapeutic

range of uid resuscitation; there is a risk for either underresuscitation or uid overload
Pediatric patients
Assessment parameters are altered for pediatric patients
Vital signs and WBC counts are age dependent (tables are available )
Target MAP is generally between the th and th percentiles or higher than the th
percentile for age
Pediatric patients who are in septic shock o en have a lactate level within normal range;
do not exclude sepsis based on lactate levels within normal range
May use trends in lactate level to guide resuscitation
Young children are at greater risk for respiratory collapse than older children and adults
Begin high- ow oxygen within the rst few minutes
Avoid mechanical ventilation if less invasive means of respiratory support are adequate
owing to associated increased intrathoracic pressure, which can reduce venous return and
worsen shock
If mechanical ventilation is necessary, institute lung-protective strategies (eg, high-

frequency oscillatory ventilation)
Extracorporeal membrane oxygenation is suggested for pediatric patients with refractory

respiratory failure related to septic shock and/or refractory septic shock
Vascular access is more di cult in pediatric patients but may be aided by use of
ultrasonography
Intraosseous route is an option for uid resuscitation and delivery of antibiotics and
other medications
Avoid prolonged attempts to obtain IV access if di cult and quickly move to

intraosseous route, except in children weighing less than kg for whom intraosseous
access is contraindicated
All emergency medications can be administered via interosseous route
As soon as access is obtained, administer isotonic crystalloids (preferred) or albumin
Balanced/bu ered crystalloids (eg, lactated Ringer solution) are preferred over . %
saline unless there is a speci c indication for an alternative type of uid
Give bolus of to mL/kg over to minutes and repeat as needed, to a total of

to mL/kg, aiming to restore age-appropriate blood pressure and heart rate, capillary
re ll ( seconds or less), strong peripheral pulses, urine output (more than
mL/kg/hour), and mentation
A pump may be required to deliver such volume at the necessary rate
Vasopressors and inotropic agents may be required earlier in pediatric patients owing to
limited ability to increase heart rate beyond higher baseline rates typical in children
Either epinephrine or norepinephrine is the rst line agent given when hemodynamic
parameters do not improve with uids ( to mL/kg) or when signs of uid overload
preclude further uid resuscitation
May consider adjunctive hydrocortisone for children with septic shock refractory to uid
and vasoactive-inotropic therapy
Give stress doses of hydrocortisone to children with acute or chronic corticosteroid

exposure, hypothalamic-pituitary-adrenal axis disorders, congenital adrenal hyperplasia, or
recent treatment with ketoconazole or etomidate
Hypoglycemia and hypocalcemia are common in children with sepsis; the former may be an
indicator of adrenal insu ciency
Pediatric patients are at increased risk for toxic shock; clindamycin (in addition to primary
antistaphylococcal or antistreptococcal therapy) and antitoxin therapy (eg, IV
immunoglobulin) are recommended for toxic shock syndrome with refractory hypotension
Up to % of children with sepsis do not have an obvious source of infection
Monitoring
Monitor blood pressure, heart rate, mean arterial pressure (for patients with shock), and urine
output continuously during uid resuscitation
Monitor serum lactate levels every hours to guide uid resuscitation
Follow published recommendations for dosing and monitoring if treating with vancomycin
Serum procalcitonin, although not considered to be diagnostic for sepsis, may be monitored as
a way to determine when antibiotics may be safely discontinued
Complications and Prognosis
Complications
Ventilator-associated pneumonia (Related: Hospital-Acquired and Ventilator-Associated
Pneumonias)
End-organ dysfunction (eg, renal, pulmonary)
Deep vein thrombosis (Related: Deep Vein Thrombosis)
Stress ulcer
Physical, cognitive, and emotional disabilities
Prognosis
Mortality rate varies depending on response to treatment and severity at presentation
With sepsis, now de ned as including organ failure (since ), the most relevant portion of
the evidence base from before is the portion reporting on categories of "severe sepsis and
septic shock" (as then de ned)
Under those de nitions, some representative reports gave mortality ranges as follows:
Severe sepsis: % to %
Septic shock: % to %
In septic shock, mortality increases by . % for every hour that appropriate antimicrobial
medications are delayed
Patients who survive sepsis have a higher mortality rate a er discharge as well as higher
incidences of persistent pulmonary dysfunction, physical disability, cognitive dysfunction, and
posttraumatic stress disorder
Screening and Prevention
Prevention
Prevention of community-acquired infection
Vaccination
Annual in uenza vaccine for all persons older than months
Age-appropriate vaccines for children and adolescents
Pneumococcal vaccines for older adults
Other vaccines (eg, meningococcus, Haemophilus species) as recommended for persons

with chronic conditions or immunode ciency
Wound care
Personal hygiene
Prevention of medical care–associated infection
Proper hand hygiene and general infection control measures
Oral care and positioning to prevent hospital-acquired pneumonia and ventilator-associated

pneumonia

Sepsis - ClinicalKey

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Sepsis - ClinicalKey

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12/6/24, 10:12 p.m.

Early lactate measurement is key to recognizing sepsis; delay is associated with

Measure lactate level

Obtain blood specimens for culture

Administer broad-spectrum antibiotics

For patients with hypotension or lactate levels of mmol/L or higher

Administer isotonic crystalloid uids; goal is mL/kg

If hypotension occurs or persists during or a er uid resuscitation, add

Characterized by cascade e ect of sepsis, including endothelial damage, vascular

Presentation varies depending on source of infection but o en includes fever, tachypnea,

Complications include ventilator-associated pneumonia; end-organ dysfunction; deep vein

Severe sepsis has a mortality rate of % to %

Septic shock has a mortality rate of % to %

Presentation of sepsis in older adults is o en di erent from presentation in younger people,

Clinical Clari cation

Characterized by a cascade of endothelial damage, vascular permeability, microvascular

Life-threatening organ dysfunction caused by dysregulated host response to infection

De ned as need for administration of vasopressor medication to maintain mean arterial

Common generalized symptoms of sepsis include:

Fever, chills; rigors may be reported

Nausea and vomiting

Localizing symptoms may include:

Headache and sti neck when meningitis is the cause of sepsis

Cough and pleuritic chest pain with pneumonia

Abdominal pain with gastrointestinal or genitourinary source

Diarrhea with gastrointestinal luminal infections, such as Clostridioides di cile or

Flank pain and dysuria with kidney infection

Bone or joint pain with osteomyelitis or septic arthritis

Skin or so tissue pain with abscesses, wounds, or other so tissue infections

Generalized evidence of sepsis is highly variable but commonly includes:

Fever (above . °C) or hypothermia (below °C)

Fever is the most common sign of sepsis

Presenting sign in % of patients with sepsis

Tachycardia (heart rate greater than beats per minute)

Tachypnea (respiratory rate greater than breaths per minute)

Rigors may be observed

Increased capillary re ll time (longer than seconds)

Mottled skin on inspection; petechiae may be seen with severe thrombocytopenia or

Diaphoresis; clammy skin

Cough; production of purulent or foul-smelling sputum may be observed by clinician or

Hemoptysis may be observed by clinician or reported by patient with severe pneumonia,

Dullness to percussion may indicate pleural e usion (parapneumonic e usion or

Rhonchi and/or rales on auscultation

Egophony on auscultation indicates consolidation

Abdominal distention on inspection

Decreased bowel sounds on auscultation owing to ileus

Costovertebral tenderness and suprapubic pain on palpation

Vaginal discharge or bleeding

Skin and so tissue

Wounds, ulcerations, furuncles, or carbuncles on inspection

Surgical incisions and IV sites on currently or recently hospitalized patients

There may be erythema and/or edema on inspection

Drainage may be evident, either spontaneous or expressed

Lymphadenopathy may be detected proximal to infection site

Other less common ndings may include:

Meningismus, Kernig sign, or Brudzinski sign in meningitis

Warm, swollen joint may be a site of septic arthritis

New heart murmur or change in character of a murmur suggesting endocarditis

Causes and Risk Factors

Wide range of microbial pathogens may be implicated, depending on site of primary

Common sources of infections leading to sepsis include:

Respiratory tract infections (account for % of sepsis cases)

Community-acquired pneumonia (Related: Community-Acquired Pneumonia in

Streptococcus pneumoniae and Staphylococcus aureus are commonly implicated