Acid-Base Physiology

Case 17 : An intoxicated baby

updated 29Aug2015

Clinical Details

History: An 8 month old female baby was admitted with a one day history of lethargy. She had vomited several times. Her mother said she appeared "intoxicated".

Examination: The baby was obtunded but she was easily rousable and muscle tone was normal. Resp rate was 60/min. Pupils were normal. There was no evidence of dehydration. Abdomen was soft and nontender. BP was 112/62. Peripheral perfusion was clinically assessed as normal. Heart and chest examination was normal. Plantar response was normal.

Investigations: Na+ 135, K+ 4.2, Cl- 116, HCO3- 5.7, glucose 5.9 (All in mmol/l). Urinalysis: pH 5.0, negative for glucose and ketones. Calcium oxalate crystals were seen on urine microscopy

Arterial Blood Gases

pH 7.19

pCO2 16 mmHg

pO2 110 mmHg

HCO3 6.2 mmol/l


Initial clinical assessment

The alerting information in the history is the comment about the baby appearing "intoxicated": such a CNS sign suggests a toxin such as ethylene glycol or methanol as the cause. However, an ill baby is typically listness and one should not read to much into this comment. The finding of numerous calcium oxalate crystals suppports but is not diagnostic of ethylene glycol ingestion but as this is such a serious diagnosis, it should be aggressively pursued.

There is no evidence of hypoperfusion, hyperglycaemia or ketosis. Also there is no history given of any inherited metabolic disorder which could result in a lactic acidosis, renal tubular acidosis or an organic acidosis due to an inborn error of metabolism, but these are possibilities. This amount of reported vomiting would not result in alkalosis, and the baby is too old for infantile pyloric stenosis. Unfortunately, no urea or creatinine result, or an osmolar gap is provided.

Acid-base diagnosis

  1. pH The severe acidaemia indicates a severe acidosis is present
  2. Pattern: The pattern of a low bicarbonate & low pCO2 indicates that this is a metabolic acidosis
  3. Clues: The anion gap is normal (ie 135-116-5.7 = 13.3mmol/l) and the chloride is raised. Delta ratio = (Increase in AG / decrease in HCO3) = (13.3-12)/(24-6) = 0.07 This means a normal anion gap metabolic acidosis
  4. Compensation: The expected pCO2 is (1.5 x 6.2 + 8) = 17.3mmHg. The actual pCO2 is close so respiratory compensation is maximal. It takes 12 to 24 hours for compensation to reach this maximal level & the history indicates sufficient time has passed
  5. Formulation: A normal anion gap (or hyperchloraemic) metabolic acidosis with maximal respiratory compensation. There is no evidence of a respiratory disorder, and the low delta ratio <0.4) indicates a 'pure' NAGMA.
  6. Confirmation: See below. Osmolar gap result is useful in metabolic acidosis if the cause is not obvious; an elevated value indicates the presence of an excessive amount of a low molecular solute (such as occurs in some ingestions (methanol, ethanol, ethylene glycol)).

Clinical Diagnosis

A normal anion gap metabolic acidosis may be due to a GIT cause (e.g. diarrhoea), a renal cause (e.g. renal tubular acidosis), or infusion of certain solutions (e.g. ammonium chloride, excessive normal saline infusion).

There is no history or examination findings supporting a GIT cause. The urine pH is 5 which is appropriately low and so does not support a diagnosis of type 1 (or distal) renal tubular acidosis. The absence of hypokalaemia & the severity of the acidosis are also against the diagnosis of a type 2 renal tubular acidosis. There is no history of drug (eg acetazolamide) or toxin ingestion. There is no ketoacidosis. There have been no intravenous infusions.

The cause of the acidosis is not clear. None of the usual causes of a hyperchloraemic acidosis have been found, and the predominant sign in the history (lethargy or 'intoxication') has not been explained. The lethargy suggests a drug/toxin ingestion or a metabolic disorder.


This patient was worked up looking for an inherited metabolic defect. Most organic acidaemias present soon after birth. Analysis of plasma amino acids indicated a high glycine level. Chromatography of serum (searching for organic acids) detected a large glycolic acid peak. This strongly points to ethylene glycol ingestion as the diagnosis. Ethylene glycol inself is nontoxic but it is converted in the liver to toxic metabolites (such as glycolic acid) which are responsible for the acidosis. The distinctive calcium oxalate dihydrate crystals (distinctive folded envelope appearance) were found in the urine and this further supports the diagnosis, though such crystals are common in urine and so are supportive but not diagnostic.

Ethylene glycol ingestion typically causes a high anion gap acidosis so the predominantly hyperchloraemic acidosis in this case is unexplained. In some reported cases, the anion gap has not been elevated (Eder et al 1998, Soghoian 2009). One cause is the typical progression of the ingestion: firstly there is a high ethylene glycol level (and consequent CNS signs) but a normal anion gap (latent phase; no toxic acids yet produced), then as ethylene glycol is metabolised to glycolic, glyoxylic and oxalic acid, the anion gap rises and these toxic acids cause organ damage. As a severe acidosis was present in this case, a high anion gap was expected. In adults, concurrent ingestion of ethanol can delay metabolism of ethylene glycol and such patients can have a normal anion gap (Ammar and Heckerling 1996).

Typically the combination of an increased osmolar gap and an increased anion gap alerts the clinician to the possible presence of methanol or ethylene glycol toxicity. Simultaneous measurement of both gaps is useful in patients with metabolic acidsosis when the cause is obscure.

1. Conditions which typically present with a high anion gap acidosis may sometimes present with a normal anion gap acidosis.
2. An osmolar gap is useful in assessment of metabolic acidosis particularly when the cause is not obvious.

This is Case 2 reported in Saladino and Shannon (1991).


  1. Ammar and Heckerling Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap. Am J Kidney Dis 1996 Jan;27(1):130-3
  2. Eder et al Ethylene glycol poisoning: toxicokinetic and analytical factors affecting laboratory diagnosis Clin Chem 1998; 44: 168-177
  3. Heckerling Ethylene glycol poisoning with a normal anion gap due to occult bromide intoxication. Ann Emerg Med 1987 Dec;16(12):1384-6
  4. Saladino and Shannon Accidental and intentional poisonings with ethylene glycol in infancy: diagnostic clues and management Pediatric Emergency Care 1991; 7: 93-96
  5. Soghoian et al Ethylene glycol toxicity presenting with non-anion gap metabolic acidosis Basic Clin Pharmacol Toxicol 2009 Jan;104(1):22-6