Overview
Definition:
Anion gap metabolic acidosis (AGMA) in pediatrics is a state characterized by a reduced serum bicarbonate level and an elevated anion gap (typically >12 mEq/L), indicating the presence of unmeasured anions
This signifies a primary acid-base disorder requiring urgent evaluation and management.
Epidemiology:
AGMA can occur at any age but has specific pediatric etiologies
Common causes in neonates include perinatal asphyxia and inborn errors of metabolism
In older children, diabetic ketoacidosis (DKA), sepsis, and toxic ingestions are more prevalent
The incidence varies based on underlying conditions.
Clinical Significance:
AGMA represents a serious metabolic derangement that can lead to multisystem organ dysfunction if untreated
Rapid identification of the underlying cause is critical for effective intervention, preventing life-threatening complications such as cerebral edema, arrhythmias, and shock, and improving patient outcomes in the pediatric population.
Clinical Presentation
Symptoms:
Tachypnea or Kussmaul respirations
Lethargy and decreased activity
Vomiting and abdominal pain
Dehydration
Altered mental status, ranging from irritability to coma
Specific symptoms related to the underlying etiology, e.g., fruity breath odor in DKA, hypothermia in sepsis.
Signs:
Profound tachypnea is a hallmark
Tachycardia may be present
Hypotension can indicate hypovolemia or shock
Signs of dehydration (dry mucous membranes, decreased skin turgor)
Altered level of consciousness
Specific organ system findings related to the cause (e.g., hepatomegaly in IEM).
Diagnostic Criteria:
Serum bicarbonate < 22 mEq/L
Elevated anion gap > 12 mEq/L
Formula for anion gap = [Na+] - ([Cl-] + [HCO3-])
Normal anion gap is typically 8-12 mEq/L
Diagnosis is confirmed with a metabolic panel showing low bicarbonate and elevated anion gap.
Diagnostic Approach
History Taking:
Detailed history of presenting illness, including onset and duration of symptoms
Previous medical history, especially of metabolic disorders, diabetes, or renal disease
Review of systems for clues to underlying etiology
Recent illnesses, fevers, or infections
Potential toxic exposures or ingestions
Dietary history
Family history of metabolic diseases.
Physical Examination:
Complete physical examination with a focus on vital signs (HR, RR, BP, Temp)
Assess hydration status thoroughly
Evaluate neurological status (GCS)
Examine abdomen for tenderness or organomegaly
Assess for signs of infection, trauma, or specific ingestions (e.g., breath odor, skin lesions).
Investigations:
Essential: Serum electrolytes with calculated anion gap, BUN, creatinine, glucose, venous or arterial blood gas (pH, pCO2, HCO3-)
Consider: Serum lactate, ketones (serum or urine), liver function tests, renal function panel, toxicology screen, ammonia levels, specific enzyme assays for suspected inborn errors of metabolism, imaging (chest X-ray if respiratory symptoms)
Interpretation: An elevated anion gap points to an endogenous or exogenous acid accumulation
The degree of acidosis and hyperlactatemia can indicate severity.
Differential Diagnosis:
The mnemonic "MUDPILES" or "GOLDMARK" is useful but needs pediatric adaptation: Methanol, Uremia, Diabetic Ketoacidosis (DKA), Paraldehyde/Propylene glycol, Iron/Isoniazid, Lactic Acidosis, Ethylene Glycol, Salicylates
In pediatrics, add: Inborn Errors of Metabolism (IEM), sepsis, acute kidney injury (AKI)
Differentiating features include glucose levels (DKA/DM), lactate levels (lactic acidosis), presence of toxins (methanol, ethylene glycol, salicylates), history of poor feeding or vomiting (IEM), fever and leukocytosis (sepsis).
Management
Initial Management:
Airway, breathing, circulation (ABC) assessment and support
Secure intravenous access
Rapid correction of dehydration with isotonic fluids (e.g., Normal Saline)
Glucose monitoring and appropriate dextrose administration if hypoglycemia or DKA is suspected
Sodium bicarbonate administration is controversial and should be reserved for severe acidosis (pH <7.1) with hemodynamic compromise or certain specific intoxications, after careful consideration of risks and benefits.
Medical Management:
Treatment is directed at the underlying cause
For DKA: Insulin therapy (IV infusion), fluid resuscitation, and electrolyte replacement (especially potassium)
For Lactic Acidosis: Address hypoperfusion, hypoxia, and treat the underlying cause
For IEM: Specific metabolic treatments, dietary modifications, or cofactor administration
For Toxic Ingestions: Antidotes (e.g., fomepizole for methanol/ethylene glycol, sodium bicarbonate for salicylates), activated charcoal, or enhanced elimination
For Sepsis: Antibiotics, fluid resuscitation, vasopressors if needed.
Surgical Management:
Rarely indicated for AGMA itself
May be required for complications or associated conditions, such as surgical management of bowel obstruction if present, or debridement of infected tissue in severe sepsis.
Supportive Care:
Continuous cardiac and hemodynamic monitoring
Neurological assessment for changes in mental status or signs of cerebral edema
Fluid and electrolyte balance monitoring
Nutritional support as tolerated, with careful attention to caloric intake and avoiding refeeding syndrome
Respiratory support if indicated (e.g., mechanical ventilation)
Management of pain and discomfort.
Complications
Early Complications:
Cerebral edema (especially in DKA), cardiac arrhythmias, hypokalemia, hypoglycemia, fluid overload, hypothermia, seizure, coma, acute kidney injury, adult respiratory distress syndrome (ARDS).
Late Complications:
Neurological deficits, impaired growth and development (especially with recurrent severe episodes or severe IEM), chronic renal insufficiency, long-term cognitive impairment.
Prevention Strategies:
Early recognition and prompt treatment of the underlying cause
Aggressive management of dehydration and electrolyte imbalances
Close monitoring of vital signs and neurological status
Adherence to established treatment protocols for specific etiologies like DKA or sepsis
Education for families regarding disease management and warning signs.
Prognosis
Factors Affecting Prognosis:
The severity of the acidosis and associated metabolic derangements
The promptness and efficacy of treatment
The specific underlying etiology (e.g., IEM can have a poorer prognosis than DKA if not managed early)
Presence of multi-organ failure
Age of the patient.
Outcomes:
With timely and appropriate management, most children with AGMA can have a good recovery
Prognosis is guarded in cases of severe intoxication, overwhelming sepsis, or advanced inborn errors of metabolism
Long-term sequelae can occur depending on the severity and duration of the insult.
Follow Up:
Regular follow-up is essential for children with underlying chronic conditions (e.g., diabetes, metabolic disorders)
Monitoring for recurrence, growth and development, and potential long-term complications
Education for families on preventative measures and recognition of early signs of relapse.
Key Points
Exam Focus:
Remember the pediatric differential for AGMA: DKA, Sepsis, IEM, Toxic Ingestions, AKI
Always calculate the anion gap correctly
Understand the role of bicarbonate therapy in pediatrics – it is often avoided unless pH is critically low and patient is unstable
Recognize signs of cerebral edema in DKA management.
Clinical Pearls:
In a child with unexplained acidosis and elevated anion gap, consider ingestions and inborn errors of metabolism early
Aggressive fluid resuscitation is paramount in most cases of AGMA
Monitor potassium closely, especially with insulin therapy or bicarbonate administration
Consider bedside ultrasound for assessing volume status.
Common Mistakes:
Not calculating the anion gap, or using an incorrect formula
Over-reliance on bicarbonate therapy without addressing the root cause
Underestimating the risk of cerebral edema in DKA
Inadequate fluid resuscitation leading to persistent shock
Failure to consider less common but critical etiologies like IEM or specific toxins.