Sepsis in Children

Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock is defined as a life-threatening systemic response syndrome caused by viruses, bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, fungi Fungi A 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: Overview, and parasites, or toxins released from these organisms. Neonates and children are particularly prone to sepsis owing to their immature immune systems. Affected individuals may present with localizing symptoms specific to a source of infection but may often complain of nonspecific systemic symptoms. Diagnosis is based on history, exam, laboratory testing, and imaging studies. A high index of suspicion, rapid diagnosis, and clinical intervention with appropriate therapy are mandatory to achieve favorable outcomes.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock is defined as a life-threatening organ dysfunction caused by a dysregulated response to a host infection.

Systematic inflammatory response syndrome criteria

Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock:

  • 2 of the SIRS criteria:
    • Tachycardia: HR > 90/minute
    • Tachypnea: RR > 20 breaths/minute
    • Fever or hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia: temperature > 38°C or < 36°C (> 100.4°F or < 95.0°F)
    • Leukocytosis, leukopenia, or bandemia: WBCs > 1,200/mm3, < 4,000/mm3, or bandemia ≥ 10%
  • Plus, a suspected or confirmed infectious source

Severe sepsis:

  • Must meet the criteria for sepsis
  • Plus, 1 of the following:
    • Hypotension Hypotension Hypotension 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 (systolic blood pressure < 90 mm Hg)
    • Organ dysfunction:
      • Cardiovascular dysfunction
      • ARDS ARDS Acute 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
      • Renal failure
      • Altered mental status
    • Lactic acid > 4 mmol

Septic shock Septic shock Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Septic shock is diagnosed during treatment when vasopressors are necessary to control hypotension. Sepsis and Septic Shock is severe sepsis that is unresponsive to fluid resuscitation.

Mortality-rates-in-shock

Mortality rates in sepsis, severe sepsis, and septic shock Shock Shock 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:
SIRS: systemic inflammatory response syndrome
ARDS ARDS Acute 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: acute respiratory distress syndrome Acute Respiratory Distress Syndrome Acute 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

Image by Lecturio.

Other sepsis-scoring criteria

  • The sequential organ failure assessment (SOFA) score and the abbreviated version (qSOFA) are a newer set of criteria.
  • SOFA and qSOFA help predict mortality associated with sepsis.
  • Can be used as an alternative to SIRS
  • Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock is suspected when 2 of the qSOFA criteria are met.
  • The 3 criteria for the qSOFA score include:
    • RR > 22 breaths/min
    • Systolic blood pressure < 100 mm Hg
    • Altered mental status

Epidemiology and Etiology

Epidemiology

  • The incidence of sepsis is inversely related to age in children.
  • Neonatal:
    • Up to 10% of newborns have an infection within the 1st month of life.
    • More common in children with birth weight < 1,500 grams
    • The most common mode of pathogen transmission is intrapartum or through an infected birth canal.
    • Vertical transmission has ↓ due to early detection and the treatment of group B strep during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Infants and children:
    • In the USA, 75,000 children are hospitalized annually for severe sepsis.
    • 65% of cases are associated with respiratory or bloodstream infections.
    • Immunizations against Streptococcus Streptococcus Streptococcus 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. Streptococcus pneumoniae and Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae have ↓ the incidence

Risk factors

  • Neonatal:
    • Immunological immaturity
    • Exposure to maternal genital tract pathogens
    • Trauma to the scalp during childbirth
    • Invasive procedures (e.g., prolonged endotracheal intubation, parenteral feeding)
    • Poor mechanical defenses (e.g., easily erodible skin Skin The 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. Structure and Function of the Skin)
    • Resistant microorganisms
  • Infants and children:
    • Age < 1 month
    • Serious injury (e.g., penetrating trauma)
    • Chronic and debilitating conditions
    • Immunosuppression (e.g., HIV infection HIV infection Human immunodeficiency virus (HIV), a single-stranded RNA virus belonging to the Retroviridae family, is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus is a sexually transmitted or blood-borne infection that attacks CD4+ T lymphocyte cells, macrophages, and dendritic cells, leading to eventual immunodeficiency. HIV Infection and AIDS)
    • Large surgical incisions
    • Indwelling or invasive devices (e.g., chest tube)
    • Frequent urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections

Etiology

  • Neonates:
    • Most common bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
      • Group B Streptococcus Streptococcus Streptococcus 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. Streptococcus (in neonates)
      • S. agalactiae
      • MRSA
      • Escherichia coli Escherichia coli The 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
      • Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus faecalis
    • Uncommon bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
      • S. pneumoniae
      • Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa
      • Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes Infections monocytogenes
      • Klebsiella Klebsiella Klebsiella 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
      • H. influenza Influenza Influenza 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/Influenzae
      • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or "walking" pneumonia. Mycoplasma hominis
    • Viruses:
      • Adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus
      • CMV
      • Enteroviruses
      • Parechoviruses
      • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus and C viruses
      • HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2
      • Human immunodeficiency virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview (HIV)
      • Parvovirus
      • Rubella virus Rubella Virus Rubella (also known as German measles or three-day measles) is caused by a single-stranded, positive-sense RNA virus of the Togaviridae family and the Rubivirus genus. Rubella only infects humans and spreads prenatally via vertical transmission or postnatally via droplet contact. Rubella Virus
      • Varicella-zoster virus Varicella-Zoster Virus Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox (VZV)
      • EBV (in immunocompromised individuals)
    • Fungi:
      • Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis spp.
      • Malassezia Malassezia Malassezia is a lipophilic yeast commonly found on the skin surfaces of many animals, including humans. In the presence of certain environments or triggers, this fungus can cause pathologic diseases ranging from superficial skin conditions (tinea versicolor and dermatitis) to invasive disease (e.g., Malassezia folliculitis, catheter-associated fungemia, meningitis, and urinary tract infections). Malassezia Fungi spp.
      • Protozoa
    • Protozoa:
      • Plasmodium species
      • Toxoplasma Toxoplasma Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host's immune status. Toxoplasma/Toxoplasmosis gondii
      • Trypanosoma cruz
  • Infants and children:
    • E. coli
    • S. aureus
    • S. pneumoniae
    • H. Influenzae type b
    • Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria meningitidis
    • Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella spp.
    • Viruses

Pathophysiology

The host’s ability to resist direct damage by the pathogen and immune system response determines if an infection can be controlled or will result in sepsis.

  • Antigen recognition → initiates the innate immune response Innate Immune Response Immunity to pathogens is divided into innate and adaptive immune responses. The innate immune response is the 1st line of defense against a variety of pathogens, including bacteria, fungi, viruses, and parasites. In essentially the same form, the innate type of immunity is present in all multicellular organisms. Innate Immune Response → secretion of cytokines → activation of the complement system, platelet-activation-factor, arachidonic acid, and inflammatory pathways, and NO release
  • Activated coagulation factors and fibrinolysis → DIC DIC Disseminated 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
  • System-wide inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → generalized vasodilation and poor organ perfusion anaerobic metabolism → lactic acidosis
  • ↓ Perfusion → multiorgan dysfunction syndrome
  • Generalized vasodilation → relative hypovolemia and, eventually, distributive shock Shock Shock 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

Clinical Presentation

Nonspecific

  • Poor feeding
  • Change in behavior
  • Lethargy
  • Altered mental status
  • ↑/↓ HR
  • Hypotension Hypotension Hypotension 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
  • Temperature instability

System specific

  • Circulatory
    • Poor perfusion:
      • Pallor and cyanosis
      • ↑ Capillary refill
      • Edema
      • Dehydration Dehydration Volume 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. Dehydration is primarily caused by decreased water intake and presents with increased thirst and can progress to altered mental status and low blood pressure if severe. Volume Depletion and Dehydration
    • Septic shock Septic shock Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Septic shock is diagnosed during treatment when vasopressors are necessary to control hypotension. Sepsis and Septic Shock:
      •  “Warm” shock Shock Shock 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:
        • Instant capillary refill
        • Bounding pulses (wide pulse pressure)
        • Warm extremities
      •  “Cold” shock Shock Shock 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:
        • ↓ Capillary refill (> 2 seconds)
        • ↓ Pulse
        • Cold extremities
        • Most common in pediatrics
  • Digestive:
    • Vomiting/ diarrhea Diarrhea Diarrhea 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
    • Abdominal distention
    • Hepatomegaly
  • Respiratory:
    • ↑/↓ RR
    • Retractions
    • Grunting
    • Nasal flaring
    • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
    • Cyanosis
    • Hypoxia (< 90% saturation)
  • Urologic:
    • Oliguria
    • Anuria
  • Neurologic:
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures or tremors
    • Apathy
    • Irritability
    • Lethargy
    • Hypotonia/hypertonia
    • Hyperreflexia
    • Full fontanelle
    • Abnormal Moro reflex
    • Irregular breathing
    • High-pitched crying
  • Hematologic:
    • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
    • Hepatosplenomegaly
    • Bleeding
  • Dermatologic:
    • Mottling
    • Petechiae
    • Purpura

Clinical progression in neonatal sepsis

Table: Clinical progression in neonatal sepsis
Initial phase Septic phase Late phase
  • The child appears ill.
  • Poor feeding
  • Lethargy
  • Unexplained tachycardia
  • GI symptoms
  • Respiratory symptoms
  • Neurologic signs
  • Urologic symptoms
  • Circulatory collapse
  • Hematologic signs

Diagnosis

Laboratory analysis

  • CBC:
    • ↑/↓ WBC count
    • ↓ Platelet count
    • ↑ Blasts
  • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes:
    • ↓ Na
    • ↓/↑ K
    • ↓ Phosphorus
    • ↓ Glucose due to ↑ metabolic demand and ↓ caloric intake
    • Serum creatinine and BUN: prerenal azotemia due to AKI AKI Acute 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
  • Blood gas:
    • Metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis
    • ↑ Lactic acid: strong predictor of mortality
    • Hypoxemia
  • Total bilirubin:
    • ↑ (> 4 mg/dL) ALT
    • ↑ Transaminases may indicate liver Liver The 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 dysfunction, HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2, or enterovirus infection
  • Blood cultures x 2 to identify the causative agent
  • PT, PTT, and INR due to coagulation disorder
  • ↓ Fibrinogen
  • ↑ D-dimer: DIC DIC Disseminated 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
  • Urinalysis and culture

Diagnostic imaging

  • Chest X-ray: if suspected pneumonia Pneumonia Pneumonia 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 or fluid overload
  • Ultrasound or CT scan of the abdomen: +/- if etiology not apparent
  • Head CT: warranted in individuals with coagulopathy and altered mental status

Management and Prevention

Management

  • Begins with stabilizing the affected individual
  • Goal-directed therapy:
    • IV access within 5 minutes
    • Fluid resuscitation within 30 minutes
    • Broad-spectrum antibiotic therapy within 60 minutes
    • Inotropic infusion within 60 minutes (in fluid-refractory shock Shock Shock 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)
    • Periodic reevaluation of:
      • Central and peripheral pulses
      • Skin perfusion (capillary refill and skin Skin The 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. Structure and Function of the Skin temperature)
      • Fluid status
      • Urine output (> 1 mL/kg/hour)
      • Systolic blood pressure
      • Mental status
      • Serum lactate levels
      • Central venous oxygen saturation (ScvO₂)
  • Resuscitation goals:
    • Mean arterial pressure Mean Arterial Pressure Mean 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
    • Urine output > 0.5 mL/kg/hour
    • Central venous pressure (CVP) 8–10 mm Hg
    • ScvO₂ > 70% or SvO₂ > 65%
  • Therapies:
    • Crystalloid solutions: starting bolus of 20 cc/kg
    • Vasopressors (e.g., norepinephrine, epinephrine)
    • Inotropic therapy (e.g., epinephrine, dopamine)
    • Calculation of the rate of infusion: dose/volume of dilution / child’s weight/time of infusion

Antibiotic therapy

  • Ideally, start as soon as possible.
    • Within the 1st hour of presentation (golden hour)
    • After obtaining culture samples
  • Empirical broad-spread antibiotics at 1st; then, tailor to cultures and antibiograms
  • Factors to consider:
    • Age
    • History
    • Comorbidities
    • Clinical situation
    • Type of infection
    • Gram staining results
  • Antibiotic therapy options:
    • < 28-weeks old: ampicillin (50 mg/kg) or vancomycin (15 mg/kg) + cefotaxime (100 mg/kg) + gentamicin (2.5 mg/kg) and acyclovir (20 mg/kg) if suspecting HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 & 2
    • > 28-weeks old:
      • Vancomycin (15 mg/kg) + ceftriaxone (75 mg/kg) or cefotaxime (100 mg/kg)
      • In immunosuppresion: vancomycin (15 mg/kg) + cefepime (75 mg/kg) or meropenem (20 mg/kg
    • In children who cannot receive penicillin: vancomycin (15 mg/kg) + meropenem (20 mg/kg) or aztreonam Aztreonam The 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 (90–120 mg/kg/day) + clindamycin (40 mg/kg)
    • In children with fungal infections: amphotericin B + caspofungin

Prevention

  • Follow vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination schedule to prevent infections.
  • Limit the use of indwelling catheters.
  • Screening for potential pathogens during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care, and management prior to birth.
  • Rectovaginal swab for group B Streptococcus Streptococcus Streptococcus 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. Streptococcus colonization at 35–37-weeks gestation, serum testing for:
    • HIV
    • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis
    • Hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus surface antigen testing
    • C. trachomatis
    • N. gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea
    • Screening for hepatitis C Hepatitis C Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C Virus antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins in high-risk women

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Differential Diagnosis

  • Pediatric meningitis Meningitis Meningitis 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: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges, which can be life threatening. Multiple microorganisms are responsible for meningitis Meningitis Meningitis 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. Symptoms vary according to age and range from bulging fontanelles in infants to nuchal rigidity in older children. Fever, headache, lethargy, and vomiting may also be present. A lumbar puncture is used for diagnosis. Management is using antibiotics.
  • Pediatric adrenal insufficiency Adrenal Insufficiency Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by autoimmune disease, infections, and malignancy, among others. Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Adrenal Insufficiency and Addison’s Disease: characterized as primary (affecting the adrenal gland) and central (hypothalamic-pituitary dysfunction), and may be congenital or acquired. Affected individuals present with hypovolemia, hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia, hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia, and hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia. Laboratory tests are used to confirm the diagnosis. Management is using saline and dextrose to regulate electrolytes.
  • Necrotizing enterocolitis Necrotizing enterocolitis Necrotizing enterocolitis (NEC) is an intestinal inflammatory process that can lead to mucosal injury and necrosis. The condition is multifactorial, with underlying risk factors that include prematurity and formula feeding. The clinical presentation varies in severity from feeding intolerance, acute findings on abdominal exam, and systemic symptoms. Necrotizing Enterocolitis: a GI disease characterized by the intestinal necrosis of a part of the intestine. Common in preterm infants and newborns who are ill. Infants present with poor feeding, abdominal distension, and signs of sepsis. Necrotizing enterocolitis Necrotizing enterocolitis Necrotizing enterocolitis (NEC) is an intestinal inflammatory process that can lead to mucosal injury and necrosis. The condition is multifactorial, with underlying risk factors that include prematurity and formula feeding. The clinical presentation varies in severity from feeding intolerance, acute findings on abdominal exam, and systemic symptoms. Necrotizing Enterocolitis is diagnosed using abdominal X-ray. Early diagnosis and antibiotics can improve outcomes. Surgical intervention may be needed.
  • Cardiogenic shock Shock Shock 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: a condition that occurs when there is circulatory collapse secondary to cardiac insult. Affected individuals present with tachycardia, hepatomegaly, cardiac gallops, murmurs, precordial heaves, and jugular venous distension. Laboratory tests aid in the diagnosis. Chest X-ray and cardiac output monitoring are useful. Management involves maintaining the airway, oxygenation, ventilation, and circulation.
  • Pediatric infective pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis: an infection of the pericardium by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, viruses, or fungi Fungi A 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: Overview. Affected individuals present with fever Fever Fever 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 and chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain that worsen with palmar pressure to the sternum and may have prodromal syndrome. Pediatric infective pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis may cause pericardial effusion Pericardial effusion Pericardial effusion is the accumulation of excess fluid in the pericardial space around the heart. The pericardium does not easily expand; thus, rapid fluid accumulation leads to increased pressure around the heart. The increase in pressure restricts cardiac filling, resulting in decreased cardiac output and cardiac tamponade. Pericardial Effusion and Cardiac Tamponade or cardiac tamponade Cardiac tamponade Pericardial effusion is the accumulation of excess fluid in the pericardial space around the heart. The pericardium does not easily expand; thus, rapid fluid accumulation leads to increased pressure around the heart. The increase in pressure restricts cardiac filling, resulting in decreased cardiac output and cardiac tamponade. Pericardial Effusion and Cardiac Tamponade and death. Laboratory tests and cardiac imaging aid in the diagnosis. Management involves pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain control and antibiotic therapy or pericardiocentesis.
  • Pediatric metabolic acidosis: an acid-base disorder that results from low serum HCO3 or high hydrogen ion concentrations. Various etiologies including hypovolemia, toxic ingestion, inborn errors of metabolism, cardiac failure, diabetic ketoacidosis Diabetic ketoacidosis Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises, chronic renal failure, and sepsis result in metabolic acidosis. Identifying and treating the underlying etiology is important in management.

References

  1. Butt, W. (2001). Septic shock. Pediatric Clinics of North America, 48(3), 601.
  2. Haslam, D.B. (2020). Epidemiology of infections. In R.M. Kliegman MD, J.W. St Geme MD, N.J. Blum MD, Shah, Samir S., MD, MSCE, Tasker, Robert C., MBBS, MD, Wilson, Karen M., MD, MPH (Eds.), Nelson Textbook of Pediatrics (pp. 99–1005.e1)
  3. Mathias, B., Mira, J.C., Larson, S.D. (2016). Pediatric sepsis. Current Opinion in Pediatrics, 28(3), 380–387.
  4. Pasman, E.A. (2021). Shock in Pediatrics Treatment & Management: Approach Considerations, Initial Resuscitation, Glucose and Calcium Stabilization. Medscape. Retrieved August 8, 2021, from https://emedicine.medscape.com/article/1833578-treatment
  5. Rhodes, A., Evans, L.E., Alhazzani, W., Levy, M.M., Antonelli, M., Ferrer, R., Dellinger, R.P. (2017). Surviving sepsis campaign: international guidelines for the management of sepsis and septic shock. Intensive Care Medicine, 43(3), 304–377.
  6. Santhanam, S. (2021). Pediatric Sepsis: Practice Essentials, Background, Pathophysiology. Medscape. Retrieved August 8, 2021, from https://emedicine.medscape.com/article/972559-overview
  7. Sarmin, M., Afroze, F., Sharifuzzaman, Alam, T., Shaly, N.J., Ahmed, T., Chisti, M.J. (2019). Predictor of death in diarrheal children under 5 years of age having severe sepsis in an urban critical care ward in Bangladesh. Global Pediatric Health, 6, 2333794X19862716.
  8. Mathias, B., Mira, J.C., Larson, S.D. (2016). Pediatric sepsis. Current Opinion in Pediatrics, 28(3), 380–387.
  9. Wood, B.P. (2020). Necrotizing Enterocolitis Imaging: Practice Essentials, Radiography, Ultrasonography. Medscape. Retrieved August 8, 2021, from https://emedicine.medscape.com/article/411616-overview

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