The septic appearing infant:The septic appearing infant:

approach and case discussionapproach and case discussion

Muhammad Waseem, MD Pediatric Emergency Medicine

Lincoln Hospital Bronx, NY

Another Sepsis Work-up

Early Discharge

New diagnoses in ED Inborn errors of metabolism Congenital anomalies

Septic-Appearing infant

ABCs Cultures & antibiotics “An ill-appearing infant is septic

until proven otherwise” but widen your differential

10-day-old-term infant drinking 3-4 oz at first

Decreased appetite & vomiting Sleepy

Case #1

“ill appearing” Flat fontanel Dry mucous membrane Enlarged liver Slight hypotonia

Glucose 25 40 (after correction)

Organic Aciduria

Presents in first 2-3 week Septic-appearing Irritability or lethargy Vomiting

Hypotonia Hepatomegaly Hypoglycemia Breath odor Sweaty feet or stale urine

Coma Seizure Respiratory distress

The basic Approach to Inborn Errors of Metabolism

“limited repertoire” of symptoms Non specific Symptoms may overlap

E.coli sepsis (galactosemia) Clinically indistinguishable

High index of suspicionHigh index of suspicion

Clinical presentations Vomiting Lethargy Coma Seizure

Jaundice Odor

Body Urine

Inborn error of metabolism

Encephalopathy without acidosis Encephalopathy with acidosis Hepatic syndrome

IEM with No Acidosis

Maple Syrup Urine disease Urea cycle defects

IEM with acidosis

Organic aciduria Lactic acidosis

Hepatic Syndrome Galactosemia

Acute Evaluation

Glucose pH & HCO3

Electrolytes Ammonia Lactate Pyruvate

Ammonia level

Susceptible to artifacts Must be placed in ice Immediate processing < 80 mcg/dL Hundreds to thousands Readily traverses BBB Central hyperventilation

Urine Organic acids Amino acids Ketones Reducing substances

Hypoglycemia Acidosis Hyperammonemia

Hyperammonemia Urea cycle defects Organic acidemia Transient hyperammonemia of the

newborn

Diagnosis of hyperammonenia

OrganicAcidemias

Citrullinemia ArgininemiaArgininoscuccinic

acidemiaHHH

syndrome

OTCDeficiency

CPS deficiency or NAG synthetase

deficiency

Transienthyperammonemia

of thenewborn

low Normal or elevated

Plasma citruline

Normal or lowHigh

Urine orotic acid

No sAA elevation

Plasma AA

No acidosis

Blood gas

sAA elevation

Acidosis

Organic acid

Urea Cycle Defects

Early respiratory alkalosis Marked elevation of ammonia Abnormal plasma amino acids

AA NH3 Urea

Urea Cycle

Urea Cycle Defects

Ornithine-transcarbamylase (OTC) Carbamyl phosphate synthetase

(CPS)

Immediate transfer for hemodialysis

10% glucose & lipids 1 g/kg Minimal proteins

Essential amino acids (0.25 g/kg)

Sodium benzoate 250 mg/kg Hippuric acid

Sodium phenylacetate 250 mg/kg Phenylacetylglutamine

Organic Acidemia (OAs)

Methylmalonic acidemia Propionic acidemia Isovaleric acidemia

Severe acidosis Ketosis Hyperammonemia Seizures Unusual odor (urine)

Neutropenia Thrombocytopenia Urine organic acid

Hydration Glucose infusion Bicarbonate

Lactic Acidosis Small for gestational age Dysmorphic features Multiorgan disease Seizures

Lactate/pyruvate ratio Elevated anion gap Arterial specimen

Galactosemia Not manifest until galactose is

introduced Most formulas contain lactose No galactose in soy formulas

Vomiting Lethargy or irritability Feeding difficulties Poor weight gain Convulsion

Jaundice Hepatomegaly Hypoglycemia

Mental Retardation Hepatic Cirrhosis E. coli Sepsis

* Reducing substances in urine

* Must be done before transfusion

Phenylketonuria Phenylalanine hydroxylase Normal at birth Mental retardation

Gradual onset Vomiting

Fair skin Blue eyes Seborrhea or eczema Hypertonia Seizure

Guthrie test Phenylalanine 48-72 hrs After protein feeding

Maple Syrup Disease Decarboxylase Branched chain amino acids

Leucine (neurotoxic) Isoleucine Valine

Precedes screening test results Normal at birth First week May present as early as 24 hours

Feeding intolerance Lethargy Hypotonia Posturing Seizures

Typical odor Burnt sugar or caramelized sugar May not be prominent

Metabolic acidosis Late finding

Hypoglycemia No improvement after correction

Newborn Screening

Phenylketonuria Maple Syrup Urine Disease Galactosemia Homocystinuria Hypothyroidism Sickle cell disease Biotinidase deficiency HIV

Case #2

4-week-old-term infant presented fussy, crying & irritable

Vomited greenish material Tachycardia Slightly distended abdomen

Malrotation &Volvulus First 2 months Intense & constant pain

Crying, drawing up their knees Poor feeding

Bilious vomiting Abdominal distension

No distension in high volvolus

Case # 3

4-week-old presented fussy with decreased appetite

Cyanotic;does not respond to O2

Tachycardic Grunting respiration No hepatomegaly Normal Chest X-ray

Methemoglobinemia Uncommon cause of cyanosis Can be a cause of death

Ferric rather than ferrous Impaired oxygen binding of Hb

Hemoglobin M Hemoglobin reductase Drugs (benzocaine-Orajel) Idiopathic (70%) Symptoms depend on the

concentration of methemoglobin

10-30% Cyanosis 30-50% Tachycardia, fatigue 50-70% Lethargy, stupor >70% Death

Cyanosis without cardiac or pulmonary disease

Oxygen-unresponsive cyanosis Cyanosis out of proportion to

symptoms

Chocolate brown blood Pulse oximeter read 90s% Normal PaO2 despite cyanosis

< 30% Not needed 30-70% Methylene blue No response Hyperbaric O2

Exchange transfusion

Methylene blue 1 mg/kg IV 10 ml 1% ampule (10 mg/ml) Reduce methHb to hemoglobin Maximum effect in 30 minutes

Ineffective in G-6PD deficiency Hemolysis in G-6PD deficiency Alter the pulse oximeter reading

Case #4

7-day-old term infant Poky eater; eats and stops Crying & irritable after eating < 1 oz Acts hungry & wants to eat again

Bounding pulse in upper extremity Weak/or no pulses in lower

extremities

Congenital Heart Defects

First week

Hypoplastic left heart syndrome TGA TAPVR Coarctation of aorta

Coarctation of aorta VSD AV canal malformation

First month

Ductal dependent lesionsDuctal dependent lesions

Coarctation of aorta Hypoplastic left heart syndrome TGA

Tricuspid atresia Pulmonary atresia

with intact ventricular septum Critical pulmonary stenosis

Prostaglandin E1

0.3 X Kg = Number of mg to be added in 50 ml

0.5 ml/hr will deliver 0.05 microgram/kg/min

Recognize life-threatening conditions

Initiate therapy even before precise conditions

Prostaglandin E1 0.05 - 0.1 microgram/kg/min

Apnea Bradycardia Hypotension Seizures Hyperthermia

Coarctation of Aorta

Decreased lower limb pulses Acute cardiovascular collapse Differential cyanosis

TGA

5% of all CHD Aorta from RV Pulmonary artery from LV

Ductus closure minimal mixing of the systemic &

pulmonary blood via foramen ovale Hypoxemia

Cyanosis Tachypnea Murmur may be absent “Egg on a stick appearance”

Hypoplsatic left heart

Both cyanotic & acyanotic 25% of all cardiac deaths in 1st wk

Pallor Tachypnea Poor perfusion

grayish blue color Poor to absent peripheral pulses

No murmur Hepatomegaly Metabolic acidosis

Case # 5

6-week-old-full-term-infant Irritability & poor feeding few days

During feeding Pallor & breathlessness

Irritable Crying-not consolable HR 160, R 50, T 990 F Intermittent grunting O2 saturation 97%

Pale, cool extremities Clear lung fields Palpable liver 4 cm 4 extremities pulse & BP equal

Anomalous Origin of LCA

Pulmonary Artery Low pressure Desaturated blood

Myocardial ischemia

2 weeks to 6 months Restlessness, irritability Incessant crying Dyspnea Pallor & sweating (> feeding)

Congestive cardiac failure Tachypnea Tachycardia Cardiomegaly Hepatomegaly

Q-wave in I, aVL & left precordium Persistent ST-elevation T-wave inversion

Case # 6 6-day-old girl, lethargic Vomiting all night Extremely irritable Enlarged clitoris with local hairs

Adrenal Hyperplasia Inborn errors of adrenal steroid Acute salt-losing crisis

2 - 5 weeks Ambiguous genitalia

21-hydroxylase deficiency 90% of all cases 1 in 15,000 live births

Male Appears normal at birth Sexual precocity appears in 6 months Large phallus Dark skin & mucous membrane

Female Enlarged clitoris Labial fusion Virilization

Electrolytes Low Na+

High K+

Glucose

Adrenal steroid profile 17-hydroxyprogesterone Markedly elevated Obtain before hydrocortisone

administration

Fluid & Electrolyte replacement Urgent 20 ml/kg Normal Saline

Hydrocortisone 25 mg IV bolus 50 mg/m2/24 hours

Hyperkalemia Far better tolerated Volume restoration Insulin & glucose contraindicated

3-year-old previously healthy girl Breathing fast 6 vomiting in 2 hours Lethargic

Case # 7

T 100.30 F, HR 156, R 60 Clear lung fields Glucose 69

Na 144 K 6 Cl 110 Urea 27

pH 7.45 PCO2 12 HCO3 8 Base deficit 12

Salicylate level 98 mg/dl

Salicylate poisoning Tachypnea & respiratory alkalosis Metabolic acidosis Fever Seizure Coma

Case # 8 15-month-old girl- fever & vomiting Sleepy but arousable Lethargic Intermittent cry followed by

vomiting

RUQ tenderness Scant bowel sounds Guaic negative stool

Intussusception Sudden onset Triad

Vomiting Colicky abdominal pain Heme-positive stool (“currant jelly”)

Target sign Soft tissue mass with 2 concentric

circles of fat density Absence of cecal gas & stool Loss of visualization of tip of liver Paucity of bowel gas (RLQ)

Normal abdominal radiographs do not rule out intussusception

3 months to 6 years 80% under 2 years Male:female 4:1

Adenoviruses (spring) Rotaviruses (summer) Rotavirus vaccine

Fluid resuscitation is important All patients are hypovolemic

Barium enema Diagnostic & therapeutic

Air enema Increased success Lower complications & radiation

Child Abuse

Intracranial hemorrhage Inconsistent history High index of suspicion

Take home messageTake home message The “septic appearing infant” is

septic until proven otherwise but think beyond!

Key to diagnosis is high index of suspicion

“Eyes can not see what the mind does not know”