Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock from uncomplicated infection. The etiology is mainly bacterial and pneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia is the most common known source. PatientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship commonly present with feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachycardiaTachycardiaAbnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Sepsis in Children, tachypneaTachypneaIncreased respiratory rate.Pulmonary Examination, hypotensionHypotensionHypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, and/or altered mentation. Septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock is diagnosed during treatment when vasopressorsVasopressorsSepsis in Children are necessary to control hypotensionHypotensionHypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension. SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock and septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock are medical emergencies, and antibiotics are given within an hour of diagnosis.
SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock: a potentially life-threatening organ dysfunction caused by a dysregulated host response to infection
Septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock:sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock with a substantial increase in mortalityMortalityAll deaths reported in a given population.Measures of Health Status risk due to circulatory and cellular/metabolic abnormalities
Epidemiology[2,5]
MortalityMortalityAll deaths reported in a given population.Measures of Health Status ranges from 20%–50% (higher in septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock)
More common in survivors:
Hospital readmission (about 40% within 3 months)
Early death
Physical and neurocognitive dysfunction
Mood disorders
Low qualityQualityActivities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps.Quality Measurement and Improvement of life
Leading cause of death in hospitalized patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
Nearly 20% of all global deaths
Higher incidenceIncidenceThe number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time.Measures of Disease Frequency in extremes of age, men, and Black people
Septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock follows in 30% of sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock cases.
Breach of skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions integrity
IV drug use
Indwelling cathetersIndwelling cathetersCatheters designed to be left within an organ or passage for an extended period of time.Pseudomonas
Etiology and Pathophysiology
Etiology[2,5]
May be community- or hospital-acquired
Source of infection:
Identified in ⅓ of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
Most commonly pneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia, followed by intra-abdominal and genitourinary infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Cultures:
Blood cultures: positive in ⅓ of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
Staphylococcus aureusStaphylococcus aureusPotentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Brain Abscess
StreptococcusStreptococcusStreptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci.StreptococcuspneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia
Most common gram-negative pathogens:
Escherichia coliEscherichia coliThe gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
KlebsiellaKlebsiellaKlebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species.Klebsiella spp.
Pseudomonas aeruginosaPseudomonas aeruginosaA species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection.Pseudomonas
FungiFungiA kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies.Mycology: reported in about 20% of cases
VirusesVirusesMinute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.Virology: reported in only 1% of cases
Pathophysiology[2,5]
Pathogen load and virulenceVirulenceThe degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors.Proteus + host genetic composition and comorbiditiesComorbiditiesThe presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.St. Louis Encephalitis Virus result in a complex, exaggerated, and prolonged host response to infection that evolves over time.
Recognition of pathogen-associated molecular patternsPathogen-Associated Molecular PatternsSepsis and Septic Shock (PAMPsPAMPsSepsis and Septic Shock) by pathogen recognition receptorsReceptorsReceptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell.Receptors on innate immune cells → inflammatory response (e.g., release of tumorTumorInflammationnecrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage factor) → tissue damage and necrotic cell deathCell deathInjurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects.Cell Injury and Death → release of damage-associated molecular patternsDamage-Associated Molecular PatternsSepsis and Septic Shock (DAMPs) → further activation of leukocytesLeukocytesWhite blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes).White Myeloid Cells: Histology → microvascular changes (endothelial cell dysfunction + coagulation and complement activationComplement ActivationThe sequential activation of serum complement proteins to create the complement membrane attack complex. Factors initiating complement activation include antigen-antibody complexes, microbial antigens, or cell surface polysaccharides.Systemic Lupus Erythematosus)
Macrovascular changes:vasodilationVasodilationThe physiological widening of blood vessels by relaxing the underlying vascular smooth muscle.Pulmonary Hypertension Drugs and hypotensionHypotensionHypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
Microvascular changes + macrovascular changes → vascular leak, edemaEdemaEdema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, intravascular volume depletionVolume depletionVolume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids.Volume Depletion and Dehydration → impaired tissue oxygenation, cellular alterations such as greater glycolysisGlycolysisGlycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis (lactate production), mitochondrial injury, and release of oxygen species → increasing organ damage
Pathophysiology of septic shock
sTNFR: soluble tumor necrosis factor receptor
LBP: Lipopolysaccharide binding protein
SkinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions and peripheral pulses:[2,5]
With progression of shockShockShock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock: relatively warm extremities and widening of pulse pressure reflecting reduced SVR and increased CO
Respiratory failureRespiratory failureRespiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure:
Symptoms of acute respiratory distress syndromeAcute Respiratory Distress SyndromeAcute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS) (ARDS) including:
Respiratory fatigueFatigueThe state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Fibromyalgia with paradoxical abdominal movement
Bilateral pulmonary infiltrates not explained by heart failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR)
Cardiac failureCardiac failureCongestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction.Heart Failure:
HypotensionHypotensionHypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
TachycardiaTachycardiaAbnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Sepsis in Children
Pulmonary ralesRalesRespiratory Syncytial Virus subsequent to pulmonary edemaPulmonary edemaPulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure.Pulmonary Edema
Acute kidney injuryAcute Kidney InjuryAcute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury (AKIAKIAcute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury):
Decreased urinary output (oliguriaOliguriaDecreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age.Renal Potassium Regulation)
AzotemiaAzotemiaA biochemical abnormality referring to an elevation of blood urea nitrogen and creatinine. Azotemia can be produced by kidney diseases or other extrarenal disorders. When azotemia becomes associated with a constellation of clinical signs, it is termed uremia.Acute Kidney Injury/uremiaUremiaA clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of renal insufficiency. Most uremic toxins are end products of protein or nitrogen catabolism, such as urea or creatinine. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.Acute Kidney Injury
DeliriumDeliriumDelirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium
ComaComaComa is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
Critical-illness polyneuropathyPolyneuropathyPolyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy and myopathyMyopathyDermatomyositis if especially prolonged intensive care unit (ICUICUHospital units providing continuous surveillance and care to acutely ill patients.West Nile Virus) stay
Chronic moderate-to-severe cognitive impairment
Other clinical/laboratory features and complications:
IleusIleusA condition caused by the lack of intestinal peristalsis or intestinal motility without any mechanical obstruction. This interference of the flow of intestinal contents often leads to intestinal obstruction. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced.Small Bowel Obstruction
Elevated liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomyenzymesEnzymesEnzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
Disseminated intravascular coagulationDisseminated intravascular coagulationDisseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
Suspect sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shockin any individual presenting with any of the following:
Infection without apparent organ dysfunction
New-onset and unexplained organ dysfunction without apparent infection
Abnormal vital signs such as feverFeverFever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachypneaTachypneaIncreased respiratory rate.Pulmonary Examination, tachycardiaTachycardiaAbnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Sepsis in Children, or low blood pressure
Surviving SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock Campaign recommends against using qSOFAqSOFAPresence of 2 of the following 3 criteria indicates a worse outcome in a patient suspected of having sepsis and triggers an immediate diagnostic workup and treatment as appropriate. Sbp < 100 mm hg, respiratory rate > 22/min, altered mental status.Types of Shock as a single screeningScreeningPreoperative Care tool for sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock because of its low sensitivity compared to NEWS or MEWS.
NEWS (National Early Warning Score):
Strongest level of evidence exists for the NEWS score
Predicts mortalityMortalityAll deaths reported in a given population.Measures of Health Status risk in individuals with sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock
Designed to evaluate mortalityMortalityAll deaths reported in a given population.Measures of Health Status in populations, but not as useful in determining individual risk
qSOFAqSOFAPresence of 2 of the following 3 criteria indicates a worse outcome in a patient suspected of having sepsis and triggers an immediate diagnostic workup and treatment as appropriate. Sbp < 100 mm hg, respiratory rate > 22/min, altered mental status.Types of Shock (quick Sequential Organ Failure AssessmentSequential Organ Failure AssessmentSepsis in Children):
No longer recommended as a solitary screeningScreeningPreoperative Care tool for sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock
Useful in predicting poor outcomes (prolonged ICUICUHospital units providing continuous surveillance and care to acutely ill patients.West Nile Virus course and death)
No longer recommended as a solitary screeningScreeningPreoperative Care tool for sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock
Relies on laboratory results, which delays diagnosis (unsuitable for triage)
TREWS (Targeted Real-Time Early Warning System):[11]
Bedside tool using artificial intelligence to screen and alert for risk of sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock
Still under investigation
SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock standard operating procedures: Initiate early interventions in individuals at moderate-to-high risk of sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock based on screeningScreeningPreoperative Care tools (formerly known as early goal directed therapy)
Initiate hour-1 bundleHour-1 BundleSepsis and Septic Shock: Closely monitor for response to interventions and criteria of septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock.
Diagnostic criteria
Criteria for sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock:[9]
Criteria for septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock:[9]
Suspected (or documented) infection
VasopressorVasopressorAcute Cholangitis therapy necessary to maintain mean arterial pressureMean Arterial PressureMean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors.Vascular Resistance, Flow, and Mean Arterial Pressure (MAP) ≥ 65 mm Hg despite adequate IV crystalloidCrystalloidIsotonic solutions of mineral salts, such as ringer’s lactate and sodium chloride (saline solution), used in fluid therapy to rehydrate blood volume.Intravenous Fluids administration
Serum lactate > 2.0 mmol/L despite adequate IV crystalloidCrystalloidIsotonic solutions of mineral salts, such as ringer’s lactate and sodium chloride (saline solution), used in fluid therapy to rehydrate blood volume.Intravenous Fluids administration
Organizes and classifies organ dysfunction related to sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock
Nervous systemNervous systemThe nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system.Nervous System: Anatomy, Structure, and Classification: Glasgow comaComaComa is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. ComascaleScaleDermatologic Examination
DopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS ≤ 5 μg/kg/min or dobutamineDobutamineA catecholamine derivative with specificity for beta-1 adrenergic receptors.Sympathomimetic Drugs (any dose)
+ 3
DopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS > 5 μg/kg/min OR epinephrineEpinephrineThe active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels.Sympathomimetic Drugs ≤ 0.1 μg/kg/min OR norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS ≤ 0.1 μg/kg/min
+ 4
DopamineDopamineOne of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement.Receptors and Neurotransmitters of the CNS > 15 μg/kg/min OR epinephrineEpinephrineThe active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels.Sympathomimetic Drugs > 0.1 μg/kg/min OR norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS > 0.1 μg/kg/min
LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy: bilirubinBilirubinA bile pigment that is a degradation product of heme.Heme Metabolism (mg/dL)
0
< 1.2
+ 1
1.2–1.9
+ 2
2–5.9
+ 3
6–11.9
+ 4
≥ 12
Coagulation: plateletsPlateletsPlatelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology × 1000/μL
0
≥ 150
+ 1
100–149
+ 2
50–99
+ 3
20–49
+ 4
< 20
KidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy: creatinine (mg/dL) or urine output
0
< 1.2
+ 1
1.2–1.9
+ 2
2–3.4
+ 3
3.4–4.9 or < 500 mL/day
+ 4
> 5.0 or < 200 mL/day
The SOFA score quantifies the number and severity of organ failure. It assesses 6 organ systems. Each organ system is given 0–4 points based on severity of involvement. The overall SOFA score ranges from 0 (no organ failure) to 24 (most severe) points.
SOFA: sequential organ failure assessment
MAP: mean arterial pressure
Assesses severity and likelihood for ICUICUHospital units providing continuous surveillance and care to acutely ill patients.West Nile Virus care
Score is based on rapid bedside assessment of:
RespirationRespirationThe act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in.Nose Anatomy (External & Internal) rate
O2 saturation
Need for supplemental O2
Temperature
Systolic blood pressure
Heart rateHeart rateThe number of times the heart ventricles contract per unit of time, usually per minute.Cardiac Physiology
Level of consciousness
Scoring:
0–4: low clinical risk
5–6: medium clinical risk → urgent assessment and next steps based on clinicianClinicianA physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients.Clinician–Patient Relationship’s judgmentJudgmentThe process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation.Psychiatric Assessment
≥ 7: high clinical risk → emergent assessment and critical care recommended
NEWS2 score is an updated version of NEWS endorsed in UK
Table: NEWS[8]
Clinical parameter
Result
Score
Respiratory rateRespiratory rateThe number of times an organism breathes with the lungs (respiration) per unit time, usually per minute.Pulmonary Examination
Heart rateHeart rateThe number of times the heart ventricles contract per unit of time, usually per minute.Cardiac Physiology
≤ 40/min
3
41–50/min
1
51–90 bpm
0
91–110/min
1
111–130/min
2
≥ 131/min
3
AVPU score
Alert
0
Voice
3
PainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
3
Unresponsive
3
Score: 0–4: low clinical risk
Score 5–6: medium clinical risk
Score ≥ 7: high clinical risk
Note: A score ≥ 3 for any individual clinical parameter requires urgent review by a clinician.
NEWS: National Early Warning Score
AVPU: alert, voice, pain, unresponsive
Supporting evaluation[6,9,14,16]
The following are often ordered in the evaluation of sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock and septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock. Workup should be guided by the clinical presentation.
Perform a thorough physical examination (including full skinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions evaluation)
Identify any indwelling cathetersIndwelling cathetersCatheters designed to be left within an organ or passage for an extended period of time.Pseudomonas or tubes
Laboratory studies:
CBC → evaluate for:
LeukocytosisLeukocytosisA transient increase in the number of leukocytes in a body fluid.West Nile Virus or leukopenia
ThrombocytopeniaThrombocytopeniaThrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
AnemiaAnemiaAnemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
Evidence of metabolic acidosisAcidosisA pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up.Respiratory Acidosis
Elevated liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: AnatomyenzymesEnzymesEnzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
UrinalysisUrinalysisExamination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically.Urinary Tract Infections (UTIs) in Children and culture
Obtain cultures from any indwelling lines or tubes
Viral panels (e.g., COVID-19COVID-19Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems)., influenzaInfluenzaInfluenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza)
Stool cultures and NAAT, including for C. difficile (if diarrheaDiarrheaDiarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea present)
Coagulation studiesCoagulation studiesCoagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders.Coagulation Studies → evaluate for DICDICDisseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
Imaging/procedures:
Chest X-rayX-rayPenetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source.Pulmonary Function Tests → pulmonary infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
Lumbar punctureLumbar PunctureFebrile Infant → if clinical signs of meningitisMeningitisMeningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
Other imaging based on signs, symptoms, and relevant history
SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock and septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock are medical emergencies and treatment should begin immediately!
Initial management[4,6,9,13,14,16]
Ideally, the following steps should begin within the 1st hour after the diagnosis of sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock.
Draw and monitor serum lactate level (remeasure if > 2 mmol/L).
Obtain 2 sets of blood cultures (positive in only 30% of patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with presumed sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock) from separate sites before initiating antibiotics.
Rapidly administer (30 mL/kg) if hypotensive (mean arterial pressureMean Arterial PressureMean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors.Vascular Resistance, Flow, and Mean Arterial Pressure < 65 mm Hg) and/or lactate ≥ 4 mmol/L.
Balanced crystalloids are preferred over normal salineNormal salineA crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy.Intravenous Fluids (when available).
AlbuminAlbuminSerum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood.Liver Function Tests should be used after large volumes of crystalloidCrystalloidIsotonic solutions of mineral salts, such as ringer’s lactate and sodium chloride (saline solution), used in fluid therapy to rehydrate blood volume.Intravenous Fluids have been administered.
NorepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS (1st choice)
Add vasopressin to reduce norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS use
Add epinephrineEpinephrineThe active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels.Sympathomimetic Drugs if MAP inadequate with norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS + vasopressin
Add dobutamineDobutamineA catecholamine derivative with specificity for beta-1 adrenergic receptors.Sympathomimetic Drugs to norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS (or use epinephrineEpinephrineThe active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels.Sympathomimetic Drugs alone) if there is evidence of cardiac dysfunction
VasopressorsVasopressorsSepsis in Children can be started peripherally and should not be delayed while awaiting central venous access.
Inability to protect airways with risk of aspiration
Persistent metabolic acidosisAcidosisA pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up.Respiratory Acidosis with pHpHThe quantitative measurement of the acidity or basicity of a solution.Acid-Base Balance < 7.20
VentilationVentilationThe total volume of gas inspired or expired per unit of time, usually measured in liters per minute.Ventilation: Mechanics of Breathing strategies for sepsis-induced acute respiratory distress syndromeAcute Respiratory Distress SyndromeAcute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS) (ARDS):
Use prone ventilationVentilationThe total volume of gas inspired or expired per unit of time, usually measured in liters per minute.Ventilation: Mechanics of Breathing for > 12 hours a day.
If use is required, use intermittent boluses of neuromuscular blocking agents rather than a continuous infusion.
Antibiotics[2,3,6,7,9,14]
Initial coverage:
Cover all likely pathogens (including fungiFungiA kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies.Mycology, if suspected) while determining source of infection.
If there is a high likelihood of multidrug-resistant (MDR) organisms, use double gram-negative coverage.
Include methicillin-resistant Staphylococcus aureusStaphylococcus aureusPotentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Brain Abscess(MRSAMRSAA strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins.Staphylococcus) coverage for high-risk patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship.
De-escalate therapy once cultures and sensitivities identify the responsible pathogens.
Should not be used in the decision to start antibiotic therapy
Can be used in conjunction with the clinical evaluation when deciding to discontinue antibiotic therapy (when the optimal duration of treatment is unclear)
Opt for the shortest duration of therapy necessary to adequately treat the infection (avoid unnecessarily long antibiotic courses).
Table: Choice of empirical antibiotic therapy in adult patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock (all antibiotics administered intravenously)
CefepimeCefepimeA fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia.Cephalosporins
MeropenemMeropenemA thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients.Carbapenems and Aztreonam or imipenem-cilastatin
AztreonamAztreonamThe carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam, ciprofloxacinCiprofloxacinA broad-spectrum antimicrobial carboxyfluoroquinoline.Fluoroquinolones, or levofloxacinLevofloxacinThe l-isomer of ofloxacin.Fluoroquinolones if allergic to beta-lactamBeta-LactamPenicillins antibiotics
PLUS: VancomycinVancomycinAntibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.Glycopeptides (or linezolidLinezolidAn oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract.Oxazolidinones) if risk of MRSAMRSAA strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins.Staphylococcus is high or if in septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock
Neutropenic (< 500 neutrophilsNeutrophilsGranular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Innate Immunity: Phagocytes and Antigen Presentation/μL)
CefepimeCefepimeA fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia.Cephalosporins
MeropenemMeropenemA thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients.Carbapenems and Aztreonam or imipenem-cilastatin
PLUS: VancomycinVancomycinAntibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.Glycopeptides (or linezolidLinezolidAn oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract.Oxazolidinones), tobramycin, and caspofunginCaspofunginA cyclic lipopeptide echinocandin and beta-(1, 3)-d-glucan synthase inhibitor that is used to treat internal or systemic mycoses.Echinocandins
CeftriaxoneCeftriaxoneA broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.Cephalosporins
LevofloxacinLevofloxacinThe l-isomer of ofloxacin.Fluoroquinolones or moxifloxacinMoxifloxacinA fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent.Fluoroquinolones if allergic to beta-lactams
PLUS: VancomycinVancomycinAntibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.Glycopeptides (or linezolidLinezolidAn oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract.Oxazolidinones)
Associated with pneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia
Refer to the treatment of community- and ventilator-acquired pneumoniaPneumoniaPneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.Pneumonia.
Associated with severe intra-abdominal infectionsInfectionsInvasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.Chronic Granulomatous Disease
CefepimeCefepimeA fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against pseudomonas aeruginosa and may also be used in the empiric treatment of febrile neutropenia.Cephalosporins or ceftazidimeCeftazidimeSemisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for pseudomonas and other gram-negative infections in debilitated patients.Cephalosporins
MeropenemMeropenemA thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than imipenem, but does not need to be given with an enzyme inhibitor such as cilastatin. It is used in the treatment of bacterial infections, including infections in immunocompromised patients.Carbapenems and Aztreonam or imipenem-cilastatin
PLUS: MetronidazoleMetronidazoleA nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections.Pyogenic Liver Abscess
Hemodynamic treatment and monitoring[2,6,9]
Advanced monitoring options:
Arterial line:
Preferred device to monitor MAP when vasopressorsVasopressorsSepsis in Children are required; should be obtained as soon as practical
Noninvasive blood pressure measurements can be inaccurate
Central venous pressureCentral venous pressureThe blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity.Central Venous Catheter (CVPCVPThe blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity.Central Venous Catheter)
Arterial pulse contour analysis
Focused echocardiographyEchocardiographyUltrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.Tricuspid Valve Atresia (TVA) (cardiac outputCardiac outputThe volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat).Cardiac Mechanics, beat-to-beat stroke volumeStroke volumeThe amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Cardiac Cycle, and pulse pressure variation)
Can be used when advanced monitoring is not available
Includes:
Extremity temperature
SkinSkinThe skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.Skin: Structure and Functions mottling
Continued IV fluid is generally required after the initial bolus.
There is no consensus on optimal fluid therapy.
Some recommend repeated small boluses (in contrast to a continuous infusion).
Must balance correction of volume depletionVolume depletionVolume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids.Volume Depletion and Dehydration with the potential for volume overload.
The following may help guide fluid administration:
Improvement in lactate levels (keep in mind, normal levels may not be achievable in some patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship)
Vitals and CVPCVPThe blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity.Central Venous Catheter
Advanced (or alternative) monitoring findings
Respiratory support requirements (e.g., increasing requirements may signal pulmonary edemaPulmonary edemaPulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure.Pulmonary Edema)
GlucocorticoidsGlucocorticoidsGlucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs.Glucocorticoids[4,6,9,15]
Should not be used routinely
DexamethasoneDexamethasoneAn anti-inflammatory 9-fluoro-glucocorticoid.Antiemetics has been shown to reduce mortalityMortalityAll deaths reported in a given population.Measures of Health Status in patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with coronavirus disease 2019Coronavirus disease 2019Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). (COVID-19COVID-19Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems).) who are receiving respiratory support.
Weak recommendation:
Initiate IV hydrocortisoneHydrocortisoneThe main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Immunosuppressants if septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock does not respond to fluids and vasopressorsVasopressorsSepsis in Children
Consider if norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS (or epinephrineEpinephrineThe active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels.Sympathomimetic Drugs) dose is ≥ 0.25 µg/kg/min ≥ 4 hours after initiation
Dose: 50 mg IV every 6 hours (200 mg/day) → can also be given as a continuous infusion
Wean steroidsSteroidsA group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus.Benign Liver Tumors if vasopressorsVasopressorsSepsis in Children are no longer needed.
Additional measures[4,6]
Red blood cell transfusion:
Only recommended if hemoglobin is < 7 g/dL
Restrictive transfusion strategy is preferred (over liberal).
InsulinInsulinInsulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy: A blood glucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance target of 144–180 mg/dL (8–10 mmol/L) is recommended.
For stress ulcers in patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship at risk for gastrointestinal bleedingGastrointestinal bleedingGastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding
If no contraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation (active bleeding or significant thrombocytopeniaThrombocytopeniaThrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia)
Low-molecular-weight heparin (LMWH) is preferred over unfractionated heparinUnfractionated heparinA highly acidic mucopolysaccharide formed of equal parts of sulfated d-glucosamine and d-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc. , of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Anticoagulants.
Close monitoring and treatment of electrolyte abnormalities
BicarbonateBicarbonateInorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.Electrolytes:
Recommended for severe metabolic acidemiaAcidemiaRespiratory Acidosis (pHpHThe quantitative measurement of the acidity or basicity of a solution.Acid-Base Balance ≤ 7.2) and acute kidney injuryAcute Kidney InjuryAcute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
Should be initiated within 72 hours, when possible
Effectively communicate sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock status during hand-offs.
Billing and Coding
Diagnosis Codes:
These codes describe a life-threatening systemic response to infection. SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock is the initial syndrome, while septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock is a subset with profound circulatory and metabolic abnormalities. An additional code for the underlying infection is required.
Coding System
Code
Description
ICD-10-CM
A41.9
SepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock, unspecified organism
ICD-10-CM
R65.20
Severe sepsisSevere SepsisSepsis in Children without septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock
ICD-10-CM
R65.21
Severe sepsisSevere SepsisSepsis in Children with septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock
Evaluation & Workup:
This CPT code is for a serum lactate level, a critical laboratory test in the evaluation of sepsisSepsisSystemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock.Sepsis and Septic Shock. An elevated lactate level is a sign of tissue hypoperfusion and a key component in the definition of septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock.
These codes are for the immediate, life-saving interventions for septic shockSeptic shockSepsis associated with hypotension or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to lactic acidosis; oliguria; or acute alteration in mental status.Sepsis and Septic Shock. Broad-spectrumBroad-SpectrumFluoroquinolones antibiotics like piperacillinPiperacillinSemisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics.Penicillins/tazobactamTazobactamA penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria.Cephalosporins are given to treat the infection, and vasopressorsVasopressorsSepsis in Children like norepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS are used to support blood pressure.
Coding System
Code
Description
RxNorm
1148971
PiperacillinPiperacillinSemisynthetic, broad-spectrum, ampicillin derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics.Penicillins / TazobactamTazobactamA penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria.Cephalosporins (ingredient)
RxNorm
7573
NorepinephrineNorepinephrinePrecursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus.Receptors and Neurotransmitters of the CNS (ingredient)
References
Singer, M., Deutschman, C. S., Seymour, C. W., et al. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315(8), 801–810. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968574/
Kasper, D.. L, Fauci, A. S., Hauser, S. L., Longo, D. L., Jameson, J. L., Loscalzo, J. (2018). Harrison’s Principles of Internal Medicine. New York, NY: McGraw-Hill Education.
Martínez, M. L., Plata-Menchaca, E. P., Ruiz-Rodríguez, J. C., Ferrer, R. (2020). An approach to antibiotic treatment in patients with sepsis. Journal of Thoracic Disease, 12(3), 1007–1021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139065/
Yealy, D. M., et al. (2021). Early care of adults with suspected sepsis in the emergency department and out-of-hospital environment: a consensus-based task force report. Annals of Emergency Medicine, 78(1), 1–19. https://www.sciencedirect.com/science/article/abs/pii/S0196064421001177
Henry, K.E., et al. (2022). Factors driving provider adoption of the TREWS machine learning-based early warning system and its effects on sepsis treatment timing. Nature Medicine, 28(7):1447–1454. https://pubmed.ncbi.nlm.nih.gov/35864251/
National Institute for Health and Care Excellence. (2017). Sepsis: recognition, diagnosis and early management: guidance. Retrieved June 25, 2023, from https://www.nice.org.uk/guidance/ng51