Anesthesiologist, Critical Care Intensivist
Clinical Associate
Cleveland Clinic
Cleveland, Ohio
Hoang Lim, DO
Surgical ICU Fellow
Cleveland Clinic
Cleveland, Ohio

Severe high anion gap acidosis (HAGA) is an uncommon condition associated with a high mortality rate.1 It usually develops from diabetic ketoacidosis (DKA), uremia, intestinal ischemia, or side effects of medications.

A rare case of severe HAGA attributed to the combined factors of renal failure, DKA, metformin toxicity, and confounding pneumoperitoneum presented to our practice.1,2

This case highlighted the existence of Hickam’s dictum in the ICU,3 the importance of early identification of etiology, and the role of prompt treatment in acidosis reversal.


A 75-year-old black man with a past medical history of end-stage renal disease and who was on hemodialysis, had diabetes mellitus type 2 and peripheral vascular disease, and had a prior stroke presented to the emergency department with a complaint of severe abdominal pain. An acute abdominal series was positive for free air under the diaphragm (Figure 1).


Figure 1.

Chest x-ray upon patient admission, showing free air under the diaphragm.

The patient was taken to the operating room emergently for exploratory laparotomy. No evidence of perforated viscus was identified and there was no contamination within the abdomen.

The patient was transported to the surgical ICU (SICU) for further postoperative management. On arrival to the SICU, the patient remained intubated with continued severe lactic metabolic acidosis, with a lactate of 18 mmol/L, pH of 6.84, bicarbonate of 6 mmol/L, base excess of –27 mmol/L, anion gap of 48 mmol/L, creatinine level of 9.07 mg/dL, and an estimated glomerular filtration rate adjusted for a black patient of 7 mL/min/1.73 m2. The patient’s blood sugar was 271 mg/dL, with a serum beta-hydroxybutyrate of 6.6 mmol/L (normal, <0.2 mmol/L).

Immediately after arrival, the patient was started on vasopressor support, insulin drip per DKA protocol, and venovenous hemodialysis. Within 6 hours, the patient regained his neurologic function, the pressor support was reduced, his pH normalized, his lactation and anion gap were monitored over the next 2 days in the SICU, and he was discharged home on day 9 from the regular nursing floor.


Severe HAGA is a life-threatening condition that requires immediate therapy for adequate reversal.1 According to the principle of Occam’s razor, the common and simple cause of a patient’s symptoms of HAGA come from DKA, uremia, organ ischemia, or side effects from medications.1,2

In contrast, Hickam’s dictum suggests that a patient’s symptoms can arise from several diseases instead of a single cause. In our case, severe acidosis resulted from underlying uremia, DKA, concurrent use of metformin, and possible gut ischemia.3

The mainstay of treatment for severe HAGA is supportive care in addition to removal of the offending agent, with renal replacement therapies using a bicarbonate buffer (eg, hemodialysis or continuous venovenous dialysis in hemodynamically unstable patients), and insulin therapy (Figure 2). This combination of treatments allows for restoration of blood volume, enhancement of renal blood flow, correction of metabolic acidosis, and elimination of ketones, lactate, and metformin.2


Figure 2.

Arterial blood gas analysis of the patient over time. The first column shows severe metabolic acidosis. Columns 2 and 3 show the prompt response to insulin infusion and continuous renal replacement therapy.
BE, base excess; CRRT, continuous renal replacement therapy; HCO3, bicarbonate; pCO2, partial pressure of carbon dioxide; PO2, partial pressure of oxygen


Severe acidosis in critical care can result from several coexisting conditions. Early recognition and prompt therapeutic interventions are essential for acidosis reversal and achieving successful outcomes.


  1. Kiran HS, Anil GD, Sudharshana Murthy KA, et al. Severe metabolic acidosis in critically ill patients and its impact on the outcome: a prospective observational study. Int J Sci Study. 2015;3(8):168-171.
  2. Morris CG, Low J. Metabolic acidosis in the critically ill: Part 2. Causes and treatment. Anaesthesia. 2008;63(4):396-411.
  3. Mani N, Nick S, Hudson A. What three wise men have to say about diagnosis. BMJ. 2011;343:d7769.