approach to the septic-appearing infant

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Official reprint from UpToDatewww.uptodate.com ©2015 UpToDate

AuthorsRichard J Scarfone, MD, FAAPChristine Cho, MD, MPH, MEd

Section EditorsGeorge A Woodward, MDJan E Drutz, MD

Deputy Editor James F Wiley, II, MD, MPH

Approach to the septic-appearing infant

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2015. | This topic last updated: Feb 26, 2014.

INTRODUCTION — The evaluation of critically ill neonates and young infants is challenging because the clinical manifestations of illness (ie, lethargy,

poor tone, poor feeding, or irritability) are often atypical or nonspecific. Although many of these septic-appearing patients have overwhelming infections,

some may have congenital (eg, congenital adrenal hyperplasia) or acquired (eg, inflicted head injury) conditions that require prompt recognition and

specific management.

The causes of overwhelming illness among young infants who are septic-appearing are reviewed here. The evaluation and initial management decisions

are also discussed. An algorithmic approach to establishing the diagnosis is suggested (algorithm 1). Specific diagnoses are reviewed separately. The

evaluation of fever in infants less than three months of age is discussed elsewhere. (See "Evaluation and management of fever in the neonate and younginfant (younger than three months of age)".)

CAUSES — Although infection is the most likely cause of overwhelming illness among neonates and young infants, a number of other clinical conditions

have similar manifestations (table 1).

Infectious causes

Bacterial infections

®

®

Bacterial sepsis – Neonates can develop sepsis with or without localized infections such as urinary tract infections, pneumonia, or cellulitis. (See

"Definition and etiology of fever in neonates and infants (less than three months of age)", section on 'Serious bacterial infection'.)

Possible pathogens include the following:

●

In the immediate newborn period, group B streptococcus and Escherichia coli are the two most common pathogens associated with sepsis;

Listeria monocytogenes is a less common cause.

•

Beyond the first weeks of life, late-onset disease with any of these pathogens may occur, as well as infections with Streptococcus

pneumoniae, Neisseria meningitidis, and, to a much lesser extent, Haemophilus influenzae type b.

•

Infection with community acquired methicillin resistant Staphylococcus aureus (MRSA) must be considered for infants with skin infections or

with known exposures.

•

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Viral infections

(See "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum", section on 'CA-MRSA infection'

and "Methicillin-resistant Staphylococcus aureus in children: Treatment of invasive infections", section on 'Treatment approach' .)

In young infants, the origins of osteomyelitis and septic arthritis are typically hematogenous. (See "Hematogenous osteomyelitis in children:

Epidemiology, pathogenesis, and microbiology", section on 'Pathogenesis' and "Bacterial arthritis: Epidemiology, pathogenesis, and

microbiology in infants and children".)

Bacterial meningitis – Bacterial meningitis among neonates and infants is caused by the same organisms that cause sepsis. The incidence of

bacterial meningitis in this age group has been declining as the result of universal screening and intrapartum antibiotic prophylaxis for group B

Streptococcal disease and the introduction of conjugate vaccines against Haemophilus influenza type b and pneumococcus. (See "Bacterial

meningitis in the neonate: Clinical features and diagnosis" and "Bacterial meningitis in children older than one month: Clinical features and

diagnosis", section on 'Epidemiology'.)

●

Pyelonephritis – Urinary tract infections are the most common serious bacterial infections in neonates and young infants. Fewer than 10 percent of

these children will have coexisting bacteremia or urosepsis. Escherichia coli causes more than 80 percent of these infections. Clinically, it is not

possible to distinguish lower from upper urinary tract infection in this age group. A conservative and appropriate approach is to assume

pyelonephritis exists among febrile young children with pyuria. (See "Urinary tract infections in infants and children older than one month: Clinical

features and diagnosis", section on 'Younger children'.)

●

Pertussis – Pertussis is a ubiquitous and highly contagious infection with significant morbidity and mortality for young infants. Pertussis should be

considered among infants with respiratory failure, apnea and/or bradycardia, or an apparent life-threatening event (ALTE). Symptoms may be non-

specific, including feeding difficulties, tachypnea, and cough. Gagging, apnea, cyanosis, and bradycardia often develop during paroxysms of cough.

(See "Bordetella pertussis infection in infants and children: Clinical features and diagnosis", section on 'Infants' .)

●

Infant botulism – Infants develop botulism from the ingestion of Clostridium botulinum spores (air-borne or from food), rather than preformed

botulinum toxin. The toxin, which impairs impulses at the neuromuscular junction by blocking acetylcholine release, is then produced by organisms

that colonize the infant's gastrointestinal tract. Symptoms initially include hypotonia, constipation and poor feeding and progress to respiratory

failure. Most infants require intensive care and many need mechanical ventilation. The median age of presentation is four months. The disease is

more common among breast-fed infants. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism' .)

●

Overwhelming viral infection – Life-threatening viral infections among neonates are most often caused by Herpes simplex virus (HSV) or

enterovirus.

●

HSV can cause life-threatening disseminated or central nervous system infection in the newborn. As many as one-third of these neonates do

not have skin vesicles at presentation, and many are afebrile, making the diagnosis more challenging [ 1]. Initial symptoms can occur anytime

between birth and four weeks. The peak incidence of CNS disease is from 10 to 17 days of life. Those with disseminated infection may have

earlier clinical manifestations. The diagnosis should be suspected and consideration should be given to presumptive use of acyclovir among

infants less than four weeks old who have any of the following risk factors: maternal HSV, vesicular rash, seizures, CSF pleocytosis, or elevated liver enzymes. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Clinical manifestations' .)

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Congenital conditions

Enteroviral serotypes, such as group B coxsackievirus serotypes 2 to 5 and echovirus 11, may produce fulminant myocarditis or hepatitis

among neonates. The infection is most often acquired from a symptomatic mother in the perinatal period. Symptoms typically develop

between three and seven days of life. However, approximately one-third of cases have a biphasic illness with a period of one to seven days of

apparent well-being interspersed between the initial symptoms and the appearance of more serious manifestations. (See "Clinical

manifestations and diagnosis of enterovirus and parechovirus infections", section on 'Infections in neonates'.)

•

Bronchiolitis with apnea – Young infants, particularly those who are less than one month of age or who were born prematurely, may develop

apnea with bronchiolitis [2]. Some may present with severe apnea before they develop typical signs of bronchiolitis, such as respiratory distress or

wheezing. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Apnea'.)

●

Influenza – The influenza virus is highly contagious resulting in seasonal epidemics. Influenza-like illness is marked by fever and signs of lower

respiratory tract disease such as coughing. Infants may also present with vomiting, poor feeding, or malaise and along with the elderly, they suffer

the greatest morbidity and mortality. Those with significant co-morbidities such as prematurity or pulmonary or cardiac diseases are at greatest risk

for adverse outcomes. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Clinical features'.)

●

Myocarditis – Evidence of viral myocarditis has been described in association with apparent life-threatening events (ALTE) and sudden infant

death. Myocarditis in children is usually caused by enteroviruses (coxsackie B group) or adenovirus. Infants may present with a fulminant illness

characterized by signs of decreased cardiac output, including hypotension, poor pulses, and decreased perfusion. Malignant arrhythmias are

common. (See "Clinical manifestations and diagnosis of myocarditis in children".)

●

Congenital heart disease (CHD) – Infants with previously undiagnosed CHD who are seriously ill usually fall into one of three categories: cyanotic

lesions, obstructive lesions, or (rarely) a coronary artery abnormality. Infants with cyanotic or obstructive heart disease, who are dependent on blood

flow through the ductus arteriosus (DA) for pulmonary or systemic circulation, develop severe symptoms as the DA closes over several days to

several weeks of life [3]. Depending on the specific cardiac lesion and the delay in seeking care, infants may present with some combination of

respiratory distress, cyanosis, shock, or congestive heart failure. (See "Diagnosis and initial management of cyanotic heart disease in the newborn"

and "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Neonates' and "Congenital and pediatric coronary artery

abnormalities", section on 'Variations of coronary artery origin from the pulmonary artery' .)

●

Common causes of cyanotic heart disease include transposition of the great vessels, tetralogy of Fallot, truncus arteriosus, tricuspid atresia,

and total anomalous pulmonary venous return.

•

Obstructive heart lesions include hypoplastic left heart, coarctation of the aorta, and other aortic arch anomalies.•

For infants with an anomalous origin of one or more coronary arteries from the pulmonary artery, myocardial ischemia may develop as

pulmonary vascular resistance normalizes postnatally.

•

Congenital adrenal hyperplasia (CAH) – CAH is a group of inherited disorders of impaired cortisol synthesis. More than 95 percent of cases are

due to 21-hydroxylase deficiency, which classically manifests in infancy as virilization and adrenal insufficiency. Male infants are usually more

difficult to recognize and may present with adrenal crisis. Adrenal crisis typically develops within the first few days to weeks of life. Clinicalmanifestations include vomiting, diarrhea, hypovolemia, hyponatremia, hyperkalemia, hypoglycemia, and hypotension. (See "Causes and clinical

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Surgical conditions

Other causes

manifestations of primary adrenal insufficiency in children", section on 'Adrenal crisis' .)

Inborn errors of metabolism (IEM) – Although individual defects are uncommon in the general population, inborn errors of metabolism account for

a significant portion of disease among infants.

●

Several categories of IEM (amino acid disorders, organic acidemias, urea cycle disorders, disorders of carbohydrate metabolism, fatty acid

oxidation defects, and mitochondrial disorders) may present with an acute metabolic crisis that is triggered by circumstances such as intake

of protein or certain carbohydrates or infection. The deterioration typically occurs after a period of apparent well-being. As an example,

newborns with urea cycle disorders or organic acidemias generally present with an acute, severe illness characterized by lethargy, poor feeding, vomiting, and shock, with hyperammonemia and profound acidosis (algorithm 2).

•

Infants with galactosemia may present with sepsis, usually from a urinary tract infection with Escherichia coli. (See "Galactosemia: Clinical

features and diagnosis", section on 'Classic galactosemia'.)

•

Although IEM may be included in newborn screening tests, infants can present before the results are available. (See "Inborn errors of

metabolism: Metabolic emergencies" and "Newborn screening".)

•

Malrotation with volvulus – Malrotation develops as a result of an arrest of normal rotation of the embryonic gut. Abnormal mobility of the small

bowel, as the result of a narrow mesenteric base, allows the mesentery to twist. Volvulus occurs when small bowel twists around the superior

mesenteric artery, causing vascular compromise to large portions of the midgut (figure 1). This leads to ischemia and necrosis of the bowel that can

quickly become irreversible. Vomiting, which is almost always bilious, occurs in >90 percent of newborns with volvulus and is by far the most

common presenting symptom of malrotation in infancy. In one case series, 90 percent of patients were less than eight weeks of age at diagnosis

[4]. (See "Intestinal malrotation".)

●

Incarcerated hernia – An inguinal hernia develops when intraabdominal contents enter the inguinal canal through a patent processus vaginalis. An

incarceration results when the hernia cannot be reduced back into the intraabdominal cavity. Incarceration can rapidly progress to strangulation, in

which hernia contents become ischemic. Inguinal hernia is six times more common in boys and has a greater incidence among premature infants.

Incarceration develops most commonly during the first year of life. (See "Overview of inguinal hernia in children", section on 'Incarcerated mass'.)

●

Pyloric stenosis – Hypertrophy of both the circular and longitudinal muscular layers of the pylorus results in obstruction. This is a common

condition estimated to occur in about 1 of 300 live births. Patients typically come to medical attention at age three to six weeks with a complaint of

progressively worsening projectile, non-bilious emesis. Eighty percent of patients with pyloric stenosis are male [ 5]. A heightened clinical

awareness and the liberal use of ultrasound to establish the diagnosis has led to less delay in diagnosis and better outcomes. (See "Infantile

hypertrophic pyloric stenosis".)

●

Appendicitis – Neonatal appendicitis has been reported infrequently. The appendix is typically perforated at the time of diagnosis among infants.

Symptoms are nonspecific and include lethargy, irritability, and vomiting. Infants often have signs of sepsis, such as hypotension. (See "Acute

appendicitis in children: Clinical manifestations and diagnosis", section on 'Clinical manifestations' .)

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Inflicted injury – Young infants with severe inflicted injury (typically, head injury) often present with altered mental status, seizures, and/or

respiratory distress. There is usually no clear history of trauma. Since signs of external injury, such as burns or contusions are often minimal or

absent, one must maintain a high-level of suspicion. (See "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children" .)

●

Acquired metabolic conditions:●

Hyponatremia – Hyponatremia usually occurs as the result of water intoxication (intake of excessive amounts of free water), syndrome of

inappropriate antidiuretic hormone secretion, or from excessive renal losses (such as with congenital adrenal hyperplasia). Occasionally,

infants with cystic fibrosis may present with hyponatremic dehydration [6]. Young infants with hyponatremia may develop lethargy or seizures,and the seizures may be refractory to anticonvulsants until the underlying metabolic derangement is corrected. (See "Fluid and electrolyte

therapy in newborns", section on 'Hyponatremia'.)

•

Hypernatremia – Causes of hypernatremia (150 mEq/L or more) include sodium poisoning, excessive loss of free water (as can occur with

diabetes insipidus), or loss of water in excess of sodium losses. Severe hypernatremic dehydration has been reported in association with

breast feeding difficulties [7,8]. Lethargy, irritability, seizures, and/or coma may occur with hypernatremia. (See "Fluid and electrolyte therapy

in newborns", section on 'Hypernatremia'.)

•

Hypoglycemia – Several factors place infants at increased risk for hypoglycemia (plasma glucose value of ≤40 mg/dL [2.22 mmol/L]). These

include low muscle mass, diminished glycogen storage capacity, immaturity of gluconeogenesis and ketogenesis, increased glucose demand,

and decreased oral intake during times of stress. Hypoglycemia can be caused by various metabolic, endocrinologic, toxic, and infectious

etiologies. Timely recognition and treatment is crucial since prolonged and/or severe hypoglycemia can precipitate seizures and/or permanent

brain damage [9]. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia".)

•

Seizures – Seizures occur more commonly in infancy than at other times during childhood, yet they remain difficult to recognize because

generalized tonic-clonic activity typically does not to occur. Hypoxic-ischemic injury is the most common cause of neonatal seizures [ 10

]. Other

causes include infections, metabolic disturbances, trauma, structural brain disease, or drug withdrawal (table 2). (See "Etiology and prognosis of

neonatal seizures".)

●

Arrhythmias – Arrhythmias, of w hich supraventricular tachycardia is the most common, may go unrecognized. Initial signs are non-specific and t he

infant typically tolerates the rapid heart rate. Eventually, congestive heart failure develops. (See "Supraventricular tachycardia in children: AVreentrant tachycardia (including WPW) and AV nodal reentrant tachycardia", section on 'Heart failure' .)

●

Toxic exposures – Infants may become ill from exposure to environmental toxins, therapeutic or intentional overdose of medications, or (rarely)

from substances in breast milk. Conditions that result from environmental exposures include the following:

●

Methemoglobinemia – Methemoglobinemia has been described in young infants in association with severe diarrheal illness and f ollowing

exposure to oxidants (such as water or foods high in nitrites and some topical anesthetics) [ 11,12

]. Infants are susceptible to acute

methemoglobinemia because of the relative immaturity of the hemoglobin reductase enzyme system that maintains hemoglobin iron in a

reduced state. Patients with methemoglobinemia typically are cyanotic or ashen and do not improve with supplemental oxygen. Oxygen

saturation, as measured with pulse oximetry, is normal or near-normal. In addition, blood samples are dark-red, chocolate, or brownish to blue

in color and do not change with the addition of oxygen (figure 2). (See "Clinical features, diagnosis, and treatment of methemoglobinemia".)

•

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EVALUATION AND DECISION

History — Symptoms reported by caretakers of septic-appearing infants are typically nonspecific:

In contrast, the following complaints are often associated with specific conditions (table 4):

Carbon monoxide poisoning – Infants may develop carbon monoxide poisoning as the result of occult exposure from sources such as

improperly vented home heating systems or automobile exhaust fumes [ 13,14

]. The diagnosis may be difficult to make without a history of

exposure or symptomatic contacts. Presenting symptoms include lethargy and irritability. (See "Carbon monoxide poisoning".)

•

Necrotizing enterocolitis (NEC) – NEC is characterized by bowel wall necrosis that may lead to perforation (image 1

). It is most common in

premature neonates, especially those of very low birth weight. It may occur in full-term infants, usually within the first 10 days of life. Term infants

who develop NEC typically have an underlying condition, such as congenital heart disease or protracted diarrhea. Systemic signs are nonspecific

and include apnea, respiratory failure, lethargy, poor feeding, temperature instability, or hypotension resulting from septic shock in the most severe

cases. (See "Clinical features and diagnosis of necrotizing enterocolitis in newborns" .)

●

Acute bilirubin encephalopathy (ABE) – Unconjugated bilirubin is a neurotoxin, which, at very high levels, can cause encephalopathy with

permanent neurologic sequelae (kernicterus). Term infants may develop bilirubin neurotoxicity when total serum bilirubin concentrations exceed 25

mg/dL (513 µmol/L). Infants who are at increased risk for ABE include those who are


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Important features of the perinatal history include the following:

Finally, information regarding fever, vomiting, type and frequency of feeding, stooling patterns, and ill contacts may provide useful clues to the etiology of

the infant's symptoms.

Physical examination — Infants who have respiratory or circulatory compromise must be quickly identified and their conditions stabilized. (See "Initial

assessment and stabilization of children with respiratory or circulatory compromise", section on 'Evaluation' .)

By definition, infants with conditions that mimic sepsis are ill-appearing. The general appearance typically includes nonspecific features such as

irritability, lethargy, poor tone, and decreased activity. A careful physical examination may identify a combination or pattern of clinical features that

suggest the etiology of an infant's symptoms (table 6).

Features of vital signs to consider include the following:

Bilious emesis is a serious sign of bowel obstruction. In one retrospective series, 97 percent of infants with malrotation and volvulus had a history

of bilious emesis [4]. (See "Intestinal malrotation".)

●

Neonates who have been well, but develop lethargy, poor feeding, vomiting, and shock may have an inborn error of metabolism (IEM). The urine of

some infants with IEM may have an unusual odor (table 5). (See 'Congenital conditions' above.)

●

Herpes simplex virus infection must be considered for a neonate whose mother has genital vesicular lesions.●

Abnormal rhythmic movements (such as twitching, blinking or chewing) may represent seizure activity.●

Infants who develop projectile vomiting may have pyloric stenosis.●

An infant who is not moving an extremity may have osteomyelitis, septic arthritis, or a f racture.●

Maternal infections, fever, and Group B streptococcal testing and results●

Mode of delivery●

Prematurity●

Birth asphyxia●

Need for neonatal intensive care●

Length of stay in the newborn nursery●

Pulses and blood pressure measurements should be obtained in both arms and both legs. Diminished pulses and blood pressure in the lower

extremities suggest left ventricular outflow obstruction, as occurs with hypoplastic left heart syndrome, critical aortic stenosis, or coarctation of the

aorta. (See "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Blood pressure and pulses' .)

●

Lack of fever does not exclude an infectious illness.●

An infant with a heart rate over 220 beats per minute (bpm) probably has a tachyarrhythmia, most commonly supraventricular tachycardia. Sinus

tachycardia rarely exceeds 220 bpm. (See "Supraventricular tachycardia in children: AV reentrant tachycardia (including WPW) and AV nodalreentrant tachycardia", section on 'Clinical features'.)

●

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Respiratory symptoms (such as tachypnea, grunting, or retractions) may be nonspecific. However, rales and/or wheezing suggest a pulmonary disorder

or heart failure.

Features of the cardiac examination may suggest a congenital defect. (See "Diagnosis and initial management of cyanotic heart disease in the newborn",

section on 'Physical examination' and "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Clinical manifestations' .) Findings to

note include:

Abdominal distention may indicate bowel obstruction, but it is a nonspecific finding. A normal abdominal examination does not exclude serious

conditions. As an example, in one case series describing children with malrotation, 60 percent of those with volvulus had a normal abdominal

examination [4].

Skin findings may include signs of infection, such as vesicles, cellulitis, or abscess formation. Jaundice suggests acute bilirubin encephalopathy.

Acrocyanosis may be the result of poor perfusion. Infants wit h central cyanosis that does not respond to supplemental oxygen, however, may have

cyanotic heart disease or methemoglobinemia.

Physical findings that are suggestive of a specific etiology include the following:

Ancillary studies

Laboratory studies — Infants under two months of age who are septic-appearing may be seriously ill. The following laboratory studies should

generally be performed:

The presence of a heart murmur suggests cardiac disease, although the absence of a murmur does not exclude it.●

A gallop rhythm, the presence of rales, and hepatomegaly likely indicate heart f ailure.●

Infants with congenital obstructive left heart disease and respiratory distress are more likely to have cardiomegaly and diminished extremity pulses

than are infants with sepsis [15]. (See 'Congenital conditions' above.)

●

An infant with apnea, bradycardia, a focal neurologic examination, and retinal hemorrhages has an inflicted head injury until proven otherwise

(picture 1). (See "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Clinical features' .)

●

Volvulus is the probable cause of bilious emesis and abdominal distention for an infant with malrotation. [4]. (See "Intestinal malrotation".)●

In comparison to myoclonus, the amplitude of movements of a seizure is typically not altered by gentle restraint. Tachycardia and hypertension

occur more commonly during a seizure. (See "Clinical features, evaluation, and diagnosis of neonatal seizures", section on 'Autonomic signs' .)

●

Cultures of blood and urine should be obtained. Infants who are stable enough to undergo lumbar puncture (LP) should usually have cerebrospinal

fluid (CSF) sent for culture as well. LP may be deferred for those who are afebrile and for whom an alternative diagnosis (such as congenital heart

disease or volvulus) is quickly established. Specific cultures (such as of stool or a localized infection) should be obtained as indicated from the

history and physical examination.

●

Urine should be collected by urethral catheterization and sent for urinalysis (UA) and culture. An enhanced UA (microscopic analysis performed on

an uncentrifuged specimen that includes a Gram stain and cell count using a hemocytometer) improves the accuracy of UA for detecting urinary

●

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Imaging — Imaging studies should be obtained for specific indications, including the following:

tract infections. Enhanced UA should be requested, when available. (See "Urinary tract infections in infants and children older than one month:

Clinical features and diagnosis", section on 'Rapidly available tests'.)

CSF should be sent for cell count, protein, glucose, gram stain, and culture whenever a LP is performed ( table 7 and table 8). (See "Bacterial

meningitis in children older than one month: Clinical features and diagnosis", section on 'Interpretation of CSF' .) Additional testing (such as for

enterovirus or HSV) should be sent as indicated from the history and physical examination.

Herpes simplex virus (HSV) cultures of skin vesicles, oropharynx, conjunctiva, urine, blood, stool or rectum, and CSF, as well as polymerase chain

reaction (PCR) testing of CSF for HSV and liver function tests, should be performed for infants ≤28 days of age with the following risk factors:

●

Mucocutaneous vesicles•

Seizure•

CSF pleocytosis with negative Gram stain•

Mother known to have HSV•

The following chemistry tests should be sent for critically ill infants:●

Electrolytes, glucose, BUN and creatinine. Infants with hypernatremia, hyponatremia, or hypoglycemia frequently have nonspecific neurologic

symptoms, including seizures.

•

Calcium, magnesium, and phosphate levels should be determined for an infant who may have had a seizure.•

Total and direct bilirubin levels should be sent for infants who appear jaundiced.•

Blood levels for ammonia, lactate, pyruvate, as well as blood and urine ketones, should be sent when an inborn error of metabolism is suspected

(table 9 and table 10)

●

A chest radiograph should be obtained for infants wit h signs or symptoms of pulmonary or cardiac disease [ 16,17]. Infants with cardiomegaly or

abnormal cardiac silhouettes may have congenital heart disease.

●

Plain films of the abdomen are indicated for infants with abdominal distention or vomiting. Abnormalities that may be seen with necrotizing

enterocolitis (NEC) include pneumatosis intestinalis (gas within the intestinal wall), portal venous gas, or pneumoperitoneum (image 1). With

malrotation and pyloric stenosis, there may be duodenal or gastric distention with a paucity of air distally.

●

Infants with bilious emesis should receive contrasted upper gastrointestinal (UGI) studies with small bowel follow through. A duodenal bulb that

overlies the spine and/or a medially directed cecum suggests malrotation (image 2 and image 3). A corkscrew appearance in the small bowel can

be seen with volvulus (image 4).

●

An abdominal ultrasound is the preferred study to detect pyloric st enosis (image 5). A "string sign" may be seen on UGI with pyloric stenosis

(image 6).

●

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Other studies — An electrocardiogram (EKG) should be performed routinely for any infant believed to have CHD. EKG findings may suggest a

specific anatomic lesion (table 11). An injury pattern may identify infants who have myocardial ischemia as the result of aberrant coronary arteries. An

emergent echocardiogram may be needed to assess some critically ill newborns.

The hyperoxia test can help to distinguish cardiac from pulmonary disease. Oxygen saturation is measured using pulse oximetry before and while theinfant is breathing 100 percent oxygen. Oxygen saturation should improve by at least 10 percent for pulmonary causes of cyanosis [ 18]. An abnormal or

equivocal response suggests cardiac disease and must be verified by measurement of an arterial blood gas, taken from the right radial artery, while the

infant is breathing 100 percent oxygen. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Hyperoxia test' .)

Initial management decisions — Infants who are breathing spontaneously and effectively but have evidence of respiratory distress or cardiovascular

compromise require immediate resuscitation with supplemental oxygen and intravenous fluids. Other more critically ill infants may need to be supported

with bag mask or mechanical ventilation. (See "Initial assessment and stabilization of children with respiratory or circulatory compromise" and

"Emergency endotracheal intubation in children" and "Initial management of shock in children".)

Some critically ill infants may require specific life-saving interventions before definitive diagnoses have been established. In this situation, the emergency

clinician must determine the likelihood that an infant may have the diagnosis, while considering the potential harm of the treatment. Treatments that

should be considered include the following:

Antibiotics — Symptoms of overwhelming infection are notoriously nonspecific in young infants. Once cultures of blood and urine (and CSF, if

possible) have been obtained, most ill-appearing young infants should receive antibiotics (table 12). (See "Evaluation and management of fever in the

neonate and young infant (younger than three months of age)", section on 'Evaluation and management' .)

Acyclovir — Early treatment with acyclovir is associated with improved outcomes among infants with HSV infections [1,19]. However, the definitive

diagnosis may depend on culture results or other tests that are not immediately available, such as polymerase chain reaction (PCR) testing.

Since the incidence of HSV among infants is low, acyclovir should be administered selectively. Infants ≤28 days of age who are ill-appearing and have

any of the following features should receive acyclovir:

Cultures for HSV, as well as a specimen of CSF for HSV PCR, should be obtained before acyclovir is given. (See "Evaluation and management of fever

in the neonate and young infant (younger than three months of age)", section on 'Evaluation and management' .)

Prostaglandin E1 (alprostadil) — For infants with cyanotic or obstructive heart disease who are dependent on blood flow through the ductus

Infants with seizures or focal neurologic examinations should receive head computed tomography (CT). A skeletal survey (plain films of all bones)

to screen for old or new fractures should be performed when inflicted head injury is suspected. (See "Child abuse: Evaluation and diagnosis of

abusive head trauma in infants and children", section on 'Imaging' .)

●

Mucocutaneous vesicles●

Neurologic symptoms such as seizures●

CSF pleocytosis with a negative CSF Gram stain●

Red blood cells in CSF from an atraumatic lumbar puncture●

Maternal history of HSV●

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arteriosus (DA) for pulmonary or systemic circulation, severe symptoms can develop when the DA closes over the first several days to weeks of life.

Structural closure of the DA is usually completed by 2 to 3 weeks of age, making the diagnosis of a ductal-dependent cardiac defect unlikely among

infants older than 28 days. (See "Clinical manifestations and diagnosis of patent ductus arteriosus", section on 'Fetal and transitional ductal circulation' .)

For hypoxic, hemodynamically unstable infants with ductal-dependent congenital heart disease, treatment with prostaglandin E1 (PGE1, alprostadil) to

reopen the ductus arteriosus (DA) can be life-saving [20,21]. Circulation through the DA temporarily restores pulmonary or systemic blood flow while the

patient undergoes further evaluation in preparation for definitive treatment. (See "Diagnosis and initial management of cyanotic heart disease in the

newborn", section on 'Prostaglandin E1'.)

Infants ≤28 days of age who do not respond to initial resuscitative efforts and are likely to have a ductal-dependent defect, but for whom diagnosis may

be delayed (such as those who must be transferred to another facility for echocardiography), should receive PGE1, ideally after consultation with a

neonatologist or pediatric cardiologist [22]. Side effects of PGE1 infusion include hypotension, tachycardia, and apnea. Equipment to provide advanced

airway management should be readily available and infants should have reliable IV access.

PGE1 should be started as an intravenous infusion at a dose of 0.05 mcg/kg per minute. In order to limit side effects, the dose may be titrated down to

the lowest dose at which the patient's condition remains improved. Apnea is less likely with doses


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Respiratory distress — Physical findings such as tachypnea, grunting, retractions, and apnea are nonspecific signs of respiratory distress that can

occur in a number of conditions, including inflicted head injury, infant botulism, bronchiolitis, or pertussis. (See "Child abuse: Evaluation and diagnosis of

abusive head trauma in infants and children" and "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism' and "Bordetella

pertussis infection in infants and children: Clinical features and diagnosis", section on 'Infants' and 'Viral infections' above.)

Infants with wheezes and/or rales may have pneumonia, bronchiolitis, or heart failure. (See "Bronchiolitis in infants and children: Clinical features and

diagnosis", section on 'Apnea'.)

Abnormal cardiac examination — An abnormal cardiac examination that may include decreased pulses or blood pressure in the lower extremities,

the presence of a murmur or gallop, a heart rate over 220 bpm, or an injury current on EKG, suggests a cardiac condition such as congenital heart

disease, myocarditis, pericarditis, supraventricular tachycardia, or aberrant coronary arteries. (See "Diagnosis and initial management of cyanotic heart

disease in the newborn", section on 'Physical examination' and "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Clinical

manifestations' and "Clinical manifestations and diagnosis of myocarditis in children" and "Supraventricular tachycardia in children: AV reentrant

tachycardia (including WPW) and AV nodal reentrant tachycardia", section on 'Heart failure' and "Congenital and pediatric coronary artery abnormalities",

section on 'Variations of coronary artery origin from the pulmonary artery'.)

Musculoskeletal findings — Infants who are not moving an extremity or have swollen extremities or joints may have osteomyelitis, septic arthritis,

or a fracture. Inflicted injury must be considered for patients with fractures. (See "Hematogenous osteomyelitis in children: Clinical features and

complications", section on 'Birth to three months' and "Orthopedic aspects of child abuse".)

Bilious vomiting — Infants with bilious vomiting must be emergently evaluated for causes of bowel obstruction, particularly malrotation withvolvulus. (See "Intestinal malrotation" and "Overview of inguinal hernia in children", section on 'Incarcerated mass'.)

No specific clinical features — Young infants who appear to have sepsis are seriously ill and require ancillary studies to identify the cause of their

symptoms. These studies may be particularly useful for patients without specific clinical features. However, infants who are seriously ill may have very

few distinguishing clinical characteristics and relatively normal ancillary studies. Examples include some patients with sepsis, overwhelming viral

illnesses, inflicted head injury, and infant botulism.

Abnormal cerebrospinal fluid — Infants with CSF pleocytosis usually have meningitis or encephalitis. HSV infection must be considered when

there is CSF pleocytosis with no organisms on gram stain or there are red blood cells from an atraumatic lumbar puncture ( table 8). (See "Bacterial

meningitis in children older than one month: Clinical features and diagnosis", section on 'Interpretation of CSF' and "Neonatal herpes simplex virus

infection: Clinical features and diagnosis", section on 'Clinical manifestations' and "Bacterial meningitis in the neonate: Clinical features and diagnosis",

section on 'Lumbar puncture'.)

Infants who are jaundiced may have acute bilirubin encephalopathy. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and

late preterm infants", section on 'Neurologic manifestations'.)

●

Central cyanosis that does not improve when the patient is breathing 100 percent oxygen occurs with cyanotic congenital heart disease and

methemoglobinemia. Blood from patients with methemoglobinemia is dark-red, chocolate, or brownish to blue in color and does not change with the

addition of oxygen (figure 2). In addition, patients with methemoglobinemia may appear cyanotic or dusky but have normal or near-normal oxygen

saturations as measured by pulse oximetry. (See "Diagnosis and initial management of cyanotic heart disease in the newborn" and "Clinical

features, diagnosis, and treatment of methemoglobinemia".)

●

http://www.uptodate.com.dti.sibucsc.cl/contents/clinical-features-diagnosis-and-treatment-of-methemoglobinemia?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/diagnosis-and-initial-management-of-cyanotic-heart-disease-in-the-newborn?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/image?imageKey=PEDS%2F58540&topicKey=EM%2F6467&source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/clinical-manifestations-of-unconjugated-hyperbilirubinemia-in-term-and-late-preterm-infants?source=see_link&sectionName=Neurologic+manifestations&anchor=H9#H9http://www.uptodate.com.dti.sibucsc.cl/contents/bacterial-meningitis-in-the-neonate-clinical-features-and-diagnosis?source=see_link&sectionName=Lumbar+puncture&anchor=H11#H11http://www.uptodate.com.dti.sibucsc.cl/contents/neonatal-herpes-simplex-virus-infection-clinical-features-and-diagnosis?source=see_link&sectionName=CLINICAL+MANIFESTATIONS&anchor=H4#H4http://www.uptodate.com.dti.sibucsc.cl/contents/bacterial-meningitis-in-children-older-than-one-month-clinical-features-and-diagnosis?source=see_link&sectionName=Interpretation+of+CSF&anchor=H19#H19http://www.uptodate.com.dti.sibucsc.cl/contents/image?imageKey=ID%2F76324&topicKey=EM%2F6467&source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/overview-of-inguinal-hernia-in-children?source=see_link&sectionName=Incarcerated+mass&anchor=H18#H18http://www.uptodate.com.dti.sibucsc.cl/contents/intestinal-malrotation?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/orthopedic-aspects-of-child-abuse?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/hematogenous-osteomyelitis-in-children-clinical-features-and-complications?source=see_link&sectionName=Birth+to+three+months&anchor=H7#H7http://www.uptodate.com.dti.sibucsc.cl/contents/congenital-and-pediatric-coronary-artery-abnormalities?source=see_link&sectionName=VARIATIONS+OF+CORONARY+ARTERY+ORIGIN+FROM+THE+PULMONARY+ARTERY&anchor=H13#H13http://www.uptodate.com.dti.sibucsc.cl/contents/supraventricular-tachycardia-in-children-av-reentrant-tachycardia-including-wpw-and-av-nodal-reentrant-tachycardia?source=see_link&sectionName=Heart+failure&anchor=H12#H12http://www.uptodate.com.dti.sibucsc.cl/contents/clinical-manifestations-and-diagnosis-of-myocarditis-in-children?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/clinical-manifestations-and-diagnosis-of-coarctation-of-the-aorta?source=see_link&sectionName=CLINICAL+MANIFESTATIONS&anchor=H6#H6http://www.uptodate.com.dti.sibucsc.cl/contents/diagnosis-and-initial-management-of-cyanotic-heart-disease-in-the-newborn?source=see_link&sectionName=Physical+examination&anchor=H6#H6http://www.uptodate.com.dti.sibucsc.cl/contents/bronchiolitis-in-infants-and-children-clinical-features-and-diagnosis?source=see_link&sectionName=Apnea&anchor=H536690659#H536690659http://-/?-http://www.uptodate.com.dti.sibucsc.cl/contents/bordetella-pertussis-infection-in-infants-and-children-clinical-features-and-diagnosis?source=see_link&sectionName=Infants&anchor=H10#H10http://www.uptodate.com.dti.sibucsc.cl/contents/neuromuscular-junction-disorders-in-newborns-and-infants?source=see_link&sectionName=INFANT+BOTULISM&anchor=H14#H14http://www.uptodate.com.dti.sibucsc.cl/contents/child-abuse-evaluation-and-diagnosis-of-abusive-head-trauma-in-infants-and-children?source=see_link


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Abnormal chest radiograph — Lung infiltrates on a chest radiograph may represent infections (such as pneumonia or bronchiolitis) or heart failure.

Infants with cardiomegaly or abnormal cardiac silhouettes may have congenital heart disease or myocarditis.

Pyuria — An abnormal urinalysis, particularly with pyuria, suggests pyelonephritis and possible urosepsis in the ill-appearing infant. (See "Urinary

tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Microscopic exam' .)

Abnormal blood chemistries — Abnormalities in blood chemistries may help to identify a specific condition. In addition, many of these

abnormalities must be urgently treated.

SUMMARY AND RECOMMENDATIONS — Young infants who are profoundly ill are often initially presumed to have sepsis. Although that is often the

case, some patients may have other conditions that have similar, nonspecific clinical features (table 1). (See 'Causes' above.)

Acidosis is a nonspecific consequence of many disorders that may mimic sepsis, including other conditions t hat cause s hock, s uch as CAH (table

13). Acidosis may also occur with inborn errors of metabolism, methemoglobinemia, carbon monoxide poisoning, dehydration, necrotizing

enterocolitis, and appendicitis.

●

Infants with pyloric stenosis may develop hypochloremic alkalosis from loss of gastric hydrochloric acid as the result of persistent vomiting. (See

"Infantile hypertrophic pyloric stenosis", section on 'Classic presentation'.)

●

Hyponatremia may develop as the result of water intoxication (intake of excessive amounts of free water), syndrome of inappropriate antidiuretic

hormone secretion, or from excessive sodium losses (such as renal losses with CAH or losses from the skin with cystic fibrosis). (See "Fluid and

electrolyte therapy in newborns", section on 'Hyponatremia' and 'Other causes' above.)

●

Hypernatremia typically occurs as the result of sodium (salt) poisoning, excessive loss of free water (as can occur with diabetes insipidus), or loss

of water in excess of sodium losses. (See "Fluid and electrolyte therapy in newborns", section on 'Hypernatremia' and 'Other causes' above.)

●

Infants who are seriously ill are frequently hypoglycemic. Severe hypoglycemia is also associated with shock, congenital adrenal hyperplasia, and

inborn errors of metabolism. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia".)

●

Hyperammonemia is a characteristic finding in urea cycle defects, organic acidemias, fatty acid oxidation defects, and liver dysfunction ( algorithm

2).

●

Historical features, physical findings, and ancillary studies may identify a specific diagnosis (table 4 and table 6). (See 'Evaluation and decision'

above.)

●

The initial management of septic-appearing infants consists of resuscitation with supplemental oxygen and intravenous fluids. Specific interventions

include the following (see 'Initial management decisions' above):

●

Once cultures of blood and urine (and CSF, if possible) have been obtained, most ill-appearing young infants should receive antibiotics ( table

12). (See "Evaluation and management of fever in the neonate and young infant (younger than three months of age)", section on 'Neonates (0

to 28 days)' and "Evaluation and management of fever in the neonate and young infant (younger than three months of age)", section on 'Ill-

appearing infants (29 to 90 days)'.)

•

Infants ≤28 days old who have mucocutaneous vesicles, seizures, CSF pleocytosis with a negative Gram stain, or maternal herpes simplex•

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REFERENCES

1. Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics 2001; 108:223.

2. Willwerth BM, Harper MB, Greenes DS. Identifying hospitalized infants who have bronchiolitis and are at high risk for apnea. Ann Emerg Med2006; 48:441.

3. Lee C, Mason LJ. Pediatric cardiac emergencies. Anesthesiol Clin North America 2001; 19:287.

4. Bonadio WA, Clarkson T, Naus J. The clinical features of children with malrotation of the intestine. Pediatr Emerg Care 1991; 7:348.

5. Hulka F, Campbell TJ, Campbell JR, Harrison MW. Evolution in the recognition of infantile hypertrophic pyloric stenosis. Pediatrics 1997; 100:E9.

6. Ballestero Y, Hernandez MI, Rojo P, et al. Hyponatremic dehydration as a presentation of cystic fibrosis. Pediatr Emerg Care 2006; 22:725.

7. Oddie S, Richmond S, Coulthard M. Hypernatraemic dehydration and breast feeding: a population study. Arch Dis Child 2001; 85:318.

8. Shroff R, Hignett R, Pierce C, et al. Life-threatening hypernatraemic dehydration in breastfed babies. Arch Dis Child 2006; 91:1025.

9. Sperling MA, Menon RK. Differential diagnosis and management of neonatal hypoglycemia. Pediatr Clin North Am 2004; 51:703.

10. Gold, CR, Pierog, J. A rational approach to pediatric seizures. Pediatric Emergency Medicine Reports 2000; 5:121.

11. Pollack ES, Pollack CV Jr. Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med 1994; 24:652.

12. Murone AJ, Stucki P, Roback MG, Gehri M. Severe methemoglobinemia due to food intoxication in infants. Pediatr Emerg Care 2005; 21:536.

13. Piatt JP, Kaplan AM, Bond GR, Berg RA. Occult carbon monoxide poisoning in an infant. Pediatr Emerg Care 1990; 6:21.

14. O'Sullivan BP. Carbon monoxide poisoning in an infant exposed to a kerosene heater. J Pediatr 1983; 103:249.

15. Pickert CB, Moss MM, Fiser DH. Differentiation of systemic infection and congenital obstructive left heart disease in the very young infant. Pediatr Emerg Care 1998; 14:263.

16. Bramson RT, Meyer TL, Silbiger ML, et al. The futility of the chest radiograph in the febrile infant without respiratory symptoms. Pediatrics 1993;92:524.

virus (HSV) infection should receive acyclovir . HSV culture and PCR for HSV testing should ideally be obtained prior to treatment. (See

"Evaluation and management of fever in the neonate and young infant (younger than three months of age)", section on 'Acyclovir' .)

Hypoxic, hypotensive, and acidotic infants ≤28 days old, who do not respond to resuscitative efforts and are likely to have ductal-dependent

congenital heart disease (as suggested by either a failed hyperoxia test or a pulse or blood pressure gradient between the upper and lower

extremities), should receive prostaglandin E1 (alprostadil). A neonatologist or pediatric cardiologist should be consulted. (See "Diagnosis and

initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1'.)

•

Critically ill infants with signs of adrenal crisis (hyponatremia, hyperkalemia, hypoglycemia, and hypotension) should receive hydrocortisoneideally after blood has been drawn for baseline ACTH and cortisol measurements. (See "Treatment of adrenal insufficiency in children",

section on 'Adrenal crisis'.)

•

An algorithmic approach to the emergent evaluation of the septic-appearing infant can be useful (algorithm 1). (See 'Algorithmic approach' above.)●

http://-/?-http://www.uptodate.com.dti.sibucsc.cl/contents/image?imageKey=EM%2F66424&topicKey=EM%2F6467&source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/treatment-of-adrenal-insufficiency-in-children?source=see_link&sectionName=ADRENAL+CRISIS&anchor=H9#H9http://www.uptodate.com.dti.sibucsc.cl/contents/hydrocortisone-pediatric-drug-information?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/diagnosis-and-initial-management-of-cyanotic-heart-disease-in-the-newborn?source=see_link&sectionName=Prostaglandin+E1&anchor=H27#H27http://www.uptodate.com.dti.sibucsc.cl/contents/alprostadil-pediatric-drug-information?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/evaluation-and-management-of-fever-in-the-neonate-and-young-infant-younger-than-three-months-of-age?source=see_link&sectionName=Acyclovir&anchor=H15#H15http://www.uptodate.com.dti.sibucsc.cl/contents/acyclovir-pediatric-drug-information?source=see_linkhttp://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/16http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/15http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/14http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/13http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/12http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/11http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/10http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/9http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/8http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/7http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/6http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/5http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/4http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/3http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/2http://www.uptodate.com.dti.sibucsc.cl/contents/approach-to-the-septic-appearing-infant/abstract/1http://www.uptodate.com.dti.sibucsc.cl/contents/license


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17. Crain EF, Bulas D, Bijur PE, Goldman HS. Is a chest radiograph necessary in the evaluation of every febrile infant less than 8 weeks of age?Pediatrics 1991; 88:821.

18. Brousseau T, Sharieff GQ. Newborn emergencies: the first 30 days of life. Pediatr Clin North Am 2006; 53:69.

19. Kimberlin DW, Lin CY, Jacobs RF, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplexvirus infections. Pediatrics 2001; 108:230.

20. Freed MD, Heymann MA, Lewis AB, et al. Prostaglandin E1 infants with ductus arteriosus-dependent congenital heart disease. Circulation 1981;64:899.

21. Zahka, KG, Siwik, ES. Principles of medical and surgical management. In: Neonatal-perinatal Medicine, 9th, Martin, RJ, Fanaroff, AA, Walsh, MC(Eds), Mosby-Elsevier, Philadelphia 2011. Vol 2, p.1290.

22. Hallidie-Smith KA. Prostaglandin E1 in suspected ductus dependent cardiac malformation. Arch Dis Child 1984; 59:1020.

23. Kramer HH, Sommer M, Rammos S, Krogmann O. Evaluation of low dose prostaglandin E1 treatment for ductus dependent congenital heartdisease. Eur J Pediatr 1995; 154:700.

Topic 6467 Version 12.0

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GRAPHICS

Approach to the septic-appearing infant


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ABC: airway, breathing, circulation; IV: intravenous catheter; PE: physical examination; CSF: cerebrospinal fluid; CXR: chest

radiograph; HSV: herpes simplex virus; SVT: supraventricular tachycardia; CAH: congenital adrenal hyperplasia.

* Cultures of blood and urine, CBC, enhanced UA, electrolytes, glucose. For patients able to tolerate the procedure, perform lumbar

puncture unless an underlying cause is rapidly identified (eg, congenital heart disease, abusive head injury, malrotation with volvulus).

Chest radiograph and other studies (eg, serum bilirubin, arterial blood gas, EKG, or metabolic studies) may also be indicated depending

upon the clinical findings.

¶ Patients who cannot tolerate lumber puncture (LP) should have a blood culture and receive antibiotics. An LP should be performed

once the patient's condition is stabilized unless an etiology other than serious infection is identified.

Graphic 66424 Version 6.0


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Causes of the septic-appearing infant

Infections

Bacterial meningitis

Sepsis

Urinary tract

Pneumonia

Cellulitis

Omphalitis

Mastitis

Septic arthritis

Osteomyelitis

Pertussis

Infant botulism

Overwhelming viral illness

Bronchiolitis

Myocarditis

Trauma

Inflicted head injury

Uintentional injury

Neurological

Seizures

Surgical/gastrointestinal

Pyloric stenosis

Malrotation with volvulus

Incarcerated hernia

Necrotizing enterocolitis


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Appendicitis

Cardiac

Congenital heart disease

Cyanotic

Obstructive

Aberrant coronary artery

Supraventricular tachycardia

Endocrine

Congenital adrenal hyperplasia

Metabolic

Hypoglycemia

Inborn errors of metabolism

Hematologic

Acute bilirubin encephalopathy

Toxic exposures

Methemaglobinemia

Carbon monoxide poisoning

Apparent life threatening event

Kawasaki disease



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Diagnostic algorithm for initial evaluation of

hyperammonemia

ASA: argininosuccinic aciduria; CPS: carbamyl phosphate synthetase; OTC:

ormithine transcarbamylase.



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Midgut volvulus

Volvulus occurs because the narrow mesenteric base, which develops

as a result of malrotation, allows the small bowel to twist around the

superior mesenteric artery. This leads to vascular compromise of large

portions of the midgut.



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Most frequently occurring etiologies of neonatal seizures

Neonatal and hypoxic-ischemic encephalopathy

Intracranial hemorrhage

Intraventricular

Intracerebral

Subdural

Subarachnoid

Central nervous system infection

Meningitis

Encephalitis

Intrauterine

Cerebral infarction

Metabolic

Hypoglycemia

Hypocalcemia

Hypomagnesemia

Chromosomal anomalies

Congenital abnormalities of the brain

Neurodegenerative disorders

Inborn errors of metabolism

Benign neonatal convulsions

Benign familial neonatal convulsions

Drug withdrawal or intoxication

Listed in relative order of frequency. Not listed is "unknown" etiology, which is encountered in approximately 10 percent of

cases (although some in this category may be benign neonatal convulsions).

Reproduced with permission from: Mizrahi EM, Kellaway P. Diagnosis and Management of Neonatal Seizures. Lippincott-Raven, Philadelphia

1998. Copyright © 1998 Lippincott Williams & Wilkins.

http://www.lww.com/


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http://www.lww.com


http://www.lww.com/


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Methemoglobinemia

Samples of blood with varying methemoglobin levels displayed on white absorbent material.

Reproduced from: Shihana F, Dissanayake DM, Buckley NA, Dawson AH. A simple quantitative bedside

test to determine methemoglobin. Ann Emerg Med 2010; 55:184. Illustration used with the

permission of Elsevier Inc. All rights reserved.



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Radiograph of necrotizing enterocolitis in premature

infants

Plain abdominal radiographs in premature infants with necrotizing enterocolitis.

Left panel: There is marked abdominal distention due in part to dilated bowel

loops, and bubbles of gas in the bowel wall due to extensive pneumatosis

intestinalis (arrow). An orogastric tube is in place. Right panel: There is marked

abdominal distention, pneumatosis intestinalis, and a suspicion of portal venous

(arrow) and/or free intraperitoneal air.



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Differential diagnosis of an apparent life-threatening event (ALTE)

Normal (misinterpreted as abnormal behavior)

Transient choke, gag or cough during feeding

Irregular breathing of REM sleep in infants

Periodic breathing

Respiratory pauses (5 to 15 sec), and longer pauses after sigh

Acute conditions

Infections

Respiratory infections (eg, pertussis, respiratory syncytial virus, bronchiolitis)

Sepsis, meningitis, encephalitis

Gastrointestinal

Intussusception

Volvulus

Drug effect

Unintentional or intentional ingestion (eg, cold medications or ethanol)

Post-anesthesia

Metabolic decompensation

Primary inborn error of metabolism

Other endocrine, electrolyte, or metabolic disorder

Toxic exposure

Carbon monoxide

Accidental or intentional ingestion of a toxin

Child abuse

Intentional suffocation

Abusive head injury

Intentional poisoning or intoxication


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Factitious illness

Chronic conditions

Gastrointestinal

Gastroesophageal reflux

Swallowing incoordination

Cardiovascular

Arrhythmia

Cardiomyopathy

Respiratory

Aspiration, with stimulation of laryngeal chemoreceptors, causing apnea

Breath-holding spells or variant

Abnormalities of respiratory control

Immaturity or prematurity

Central hypoventilation syndrome

Upper airway obstruction

Vocal cord dysfunction

Laryngotracheomalacia

Vascular ring

Neurologic

Seizure

Vasovagal syncope

Other neurologic conditions affecting respiratory control

Apnea associated with Chiari or other hindbrain malformation

CNS hemorrhage

No definable cause

REM: rapid eye movement; CNS: central nervous system.


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Linking history and diagnosis in the septic-appearing infant

History Likely diagnosis

Mother with genital lesions Herpes simplex virus

Not using an extremity Osteomyelitis, septic arthritis, or long bone

fractureMechanism of injury not consistent with developmental ability of the child and/or

severity of injuries

Abusive head-trauma or other inflicted injury

Rhythmic twitching, brief jerks, tonic rigidity, repetitive blinking, chewing, nystagmus,

bicycling movements of extremities

Seizure

No fever; progressive weakness, poor head control, floppiness, constipation, breast fed Infant botulism

Progressively worsen ing, projectile, n on -bilious emesis Pyloric sten osis

Bilious emesis Malroataion with volvulus or other

gastrointestinal obstruction

Sweating with feeds Congenital heart disease

Unusual odors Inborn errors of metabolism



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Urinary clues to inborn errors of metabolism

Potential disorder

Urine color

Black (upon standing/oxidation) Homogentisic aciduria (alkaptonuria)

Blue Tryptophan malabsorption

Pink Disorders with hematuria, kidney stone formation

Port win e (u pon st an din g/oxidat ion ) Porph yrias

Yellow-orange Disorders with increased uric acid

Urine odor*

Acrid, sweaty feet Glutaric acidemia II

Cabbage Tyrosinemia

Fishy Trimethlylaminuria, dimethylglycinuria

Maple syrup, curry Maple syrup urine disease

Mousy Phenylketonuria

Sweaty feet Isovaleric acidemia

Sweet Beta-ketothiolase deficiency

Swimming pool Hawkinsinuria

* Only in acute phases or depending on food intake.

Adapted from: Wappner RS, Hainline BE. Inborn errors of metabolism. In: Oski's Pediatrics. Principles and Practice, 3rd ed, McMillan JA,

DeAngelis CD, Feigin RD, Warshaw JB (Eds), Lippincott, Williams & Wilkins, Philadelphia, 1999. p.1823 and Saudubray JM, Chappentier C.

Clinical phenotypes: Diagnosis/algorithms. In: Metabolic and Molecular Bases of Inherited Disease, 8th ed, Scriver CR, Beaudet AL, Sly WS,

Valle D (Eds), McGraw-Hill, New York, 2001. p.1327.



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Linking physical examination and diagnosis in the septic-appearing infant

Physical findings Likely diagnosis

Bulging fontanelle, fever Meningitis

Bulging fontanelle, no fever Hydrocephalus as with inflicted head

injurySkin vesicles Herpes simplex virus

Temperature >39°C, female or an uncircumcised male UTI

Weak cry, hypotonia, hyporeflexic, diminished or absent gag reflex, ptosis, mydriasis, weak suck,

opthalmoparesis

Infant botulism

Pyloric tumor ("olive") in the right upper quadrant Pyloric stenosis

Scrotum exam with tender swelling at the external ring, above and lateral to the pubis without

an upper limit

Incarcerated hernia

Apnea, bradycardia, temperature instability, bloody stools, abdominal distention Necrotizing enterocolitis

Murmur, gallop, hepatosplenomegaly, edema, rales, grunting, flaring, retracting Congenital heart disease

Ambiguous genitalia in females, virilization in males Congenital adrenal hyperplasia

Jaundice, opisthotonus, high-pitched cry Acute bilirubin encephalopathy

UTI: urinary tract infection.



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Dome-shaped retinal hemorrhage

Dome-shaped retinal hemorrhages may break into the vitreous.

approach to the septic-appearing infant

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