Acid-Base Disorder? Mind the Gaps

A 56 year old Russian speaking male (limited English capability) presents to the emergency department via EMS with the chief complaint of generalized abdominal pain. In triage he is noted to be rubbing his stomach and touching his lower back. He indicates that this has been bothering him for the past two hours. He is noted to be verbal in triage but appears confused and is moaning in discomfort.

A step-wise emergency approach to acid-base disorders – including the “Rule of 15” and the “Delta Gap” formulas – can help uncover processes that are hidden in the labs.  

A 56 year old Russian speaking male (limited English capability) presents to the emergency department via EMS with the chief complaint of generalized abdominal pain. In triage he is noted to be rubbing his stomach and touching his lower back. He indicates that this has been bothering him for the past two hours. He is noted to be verbal in triage but appears confused and is moaning in discomfort. A prior ED visit record indicates that the patient has some sort of “liver disease” and “EtOH abuse” history (with no prior reported home medications). His initial triage vitals are recorded as:
P- 72    RR- 18    BP- 132/76
02Sat– 97% on RA    T– unable to obtain

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The patient is placed in a treatment room to await physician evaluation. Approximately 50 minutes later, the patient is found by nursing to be unresponsive on the stretcher with agonal respirations and a questionable thready pulse. The patient is emergently intubated and ACLS protocol is initiated (two minutes of chest compressions and 1 round of epinephrine with return of a perfusing pulse). His post-event EKG shows a bifasicular block and T wave inversions in the precordial leads, raising concerns for an ischemic event. The patient has emergent imaging, including a CXR (no focal findings), a head CT (no acute process), a FAST (negative), and a bedside echo. During his bedside echo, the patient suffers a bradycardiac progressing to asystolic event requiring chest compressions (with return of a perfusing rhythm). A decision to initiate transvenous pacing is made with noted difficulty with capture. He is placed on vasopressor and ionotropic support. Soon thereafter the patient has an event concerning for “seizure-like activity”. His labs result, showing the following:
ABG: pH 6.53    pCO2 76    paO2 328
CBC: WBC 17.4    Plts 223    Hgb/HCT 16/46.5
Coags: PT 17.5    INR 1.42    PTT 34.0
BMP: Na 142    K 5.8    Cl 106; CO 25
BUN 20    Crt 1.55    Gluc 249
Ca 9.8    AG 31
AlkPhos 111    TBili 0.3
Cardiac: Myo 467    Trop 0.11    BNP 40
Ammonia 477    Lactate 10.4; EtOH <10
Hepatic: AST 88    Alb 5.0    ALT 29
Urine: remarkable for 1+ketones, 1+bld, sperm

It may be tempting to dismiss the importance of these ABG results as a common result of arrest, however, marked acidemia of this level can often cause cardiac dysrhythmias and will alter cardiac responsiveness to sympathetic stimulation by decreasing the available beta receptors. The final result is often failed respiratory compensation, leading to cardiac arrest.

In fact, in this case, the acidemia led to the patient’s arrest. Had this acidemia been recognized earlier, perhaps as part of a VBG panel, respiratory decompensation and cardiac arrest might have been averted.

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Acid-base disorders are common in the ED and it is important to adopt a stepwise approach to help focus your work-up and treatment plan when approaching patients with acid-base disequilibrium. To review, disorders of the acid-base equilibrium are delineated by the equation for the bicarbonate-carbon dioxide buffer system:

• H20 + CO2 <—> H2CO3 <—>
• H+ + HCO3-

Normal values related to this acid-base equation are relatively narrow:

• pH: 7.36 – 7.44
• pCO2: 36 – 44 mmHg
• HCO3: 22 – 36 mEq/L

Basic acid-base definitions to keep in mind (remember, only one “–emia” can exist, while multiple “-osis” can be driving the “-emia” process):

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• Acidemia: condition where the pH falls below 7.36
• Alkalemia: condition where the pH rises above 7.44
• Acidosis: increase in H+ level; underlying process driving acidemia
• Alkalosis: elevated HCO3 level; underlying process driving alkalemia
• Respiratory: change in the pCO2 (increase/decrease)
• Metabolic: change in the HCO3 (decrease/increase)

Acidemia is the most common acute metabolic acid-base disturbance presenting in the critical care patient. A basic five-step process can help simplify these patients (start off by obtaining both a BMP and an ABG):

1. Check the BMP values for abnormalities
2. Calculate the anion gap (AG); normal, up to 15
3. If an acidosis is present, apply the Rule of 15
4. If an acidosis is present, check the Delta Gap
5. For unexplained wide gap metabolic acidosis, check the osmolar gap (OG)

Applying this step-wise approach to this case:
Check the BMP values for abnormalities: The patient’s bicarbonate is noted to be “5”, concerning for a marked metabolic acidosis process. Paying attention to the bicarbonate on every patient’s BMP can often provide a lot of information regarding a potential acidosis state. This patient is also noted to have a mildly elevated creatine and glucose level.
Calculate the anion gap: The AG is calculated with the following equation, AG = Na – (HCO3 + Cl). For this patient, AG = 142 – (5 + 106); AG = 31. Remember that an elevated AG suggests a wide gap metabolic acidosis, no matter what pH value (“-emia”) exists.

If an acidosis is present, apply the Rule of 15: The HCO3 + 15 should = the pCO2 and pH (last 2 digits) {+/- to 2 digits}. This patient has a bicarbonate less than 10, leading to the use of the “Corollary to the Rule of 15”. The pCO2 should be 15 and the pH should be 7.15. This patient has a pCO2 of 76 and a pH of 6.53. A primary respiratory acidosis also exists and the ventilator should be set for a very high minute ventilation to correct the patient’s hypercarbia and respiratory acidosis. The Rule of 15 helps to predict a new set point for what adequate respiratory compensation should do the pCO2 and pH. If the Rule of 15 is broken, a second process other than just respiratory compensation exists. If the pCO2 is too low a superimposed primary respiratory alkalosis exists; if the pCO2 is too high a superimposed primary respiratory acidosis exists.

If an acidosis is present, check the Delta Gap: The Delta Gap (or gap of the gaps) evaluates for a hidden metabolic process and is based off the 1:1 concept (the increase of the anion gap should be equal to the fall in the bircarbonate). For this patient, Delta AG = Delta Bicarb change = (31-15) = (5- 24) = (16) = (19). Since 16 does not equal 19, a secondary metabolic process is occurring. In this case, the bircarbonate has fallen too low, indicating the beginnings of an accompanying hidden normal gap acidosis. This is due to his developing acute renal failure and may help indicate the need for emergent renal replacement therapy. The Delta Gap is based off the “within normal limits” upper values (AG = 15, Bicarb = 24). If a delta gap is found and the bicarbonate is too low, a hidden normal gap metabolic acidosis is present in conjunction with the wide gap acidosis. If a delta gap is found and the bicarbonate is too high, a hidden normal metabolic alkalosis is present with the wide gap acidosis.

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For unexplained wide gap metabolic acidosis, check the osmolar gap: Osmolarity is calculated with the following equation, Osm = (2Na) + (Gluc/18) + (BUN/2.8) + (EtOH/4). The OG is the measured osmolarity minus the calculated osmolarity, with a normal value of 10. To calculate the osmolarity for this patient, Osm = (2 * 142) + (249/18) + (20/2.8) + (0) = 284 + 13.8 + 7.1 + 0 = 305. This patient did not have a measured serum osmolarity sent from the emergency department for calculation of the OG. A quick rule to remember with concern for toxic alcohols is the “3, 4, 6 Estimation Rule”. Methanol equals 3 (for every 100mg/dL of methanol, the OG increases by 30), ethanol equals 4 (for every 100mg/dL of ethanol, the OG increase by 40) and ethylene glycol and isopropyl alcohol equal 6 (for every 100mg/dL, the OG increases by 60).    

Returning to the developments and progression of this case: alcohols, serum osmolality, and serum drug panels were sent to the lab and the patient was empirically started on NAC and Fomepizole therapy, in consultation with toxicology. A call was also placed to the Nephrology service for emergent dialysis due to his acidosis. As shown in the above calculations, the patient was found to have a wide gap metabolic acidosis, a hidden normal gap acidosis (a veiled early harbinger of his progressing renal failure only found by close evaluation of his acid-base status), and an accompanying respiratory acidosis. He was also noted to have a markedly elevated osmolar gap (with obvious concern for methanol intoxication versus ethylene glycol). Upon admission to the ICU, his cardiac arrhythmias abated with correction of his marked acidosis as well as resolution of his vasopressor requirements. Of note, his physical exam on arrival to the critical care setting exhibited pupils dilated to 5mm which were unresponsive to light stimuli.

The patient’s methanol level resulted from the lab approximately twelve hours later at a level of 129mg/dL (ethylene glycol was negative). Upon their arrival, his family admitted that the patient had a history of drinking windshield wiper fluid, mouthwash, perfumes… basically anything that had some sort of alcohol as an ingredient. Further searching of medical records uncovered a remote previous visit with an acute intoxication of EtOH (level of 565) requiring intubation for airway protection. The patient underwent several rounds of hemodialysis to clear his methanol toxicity. He continued off sedation throughout his critical care course with no return of a neurologic exam. On ICU day #4 he underwent a brain death exam by the Neurology service. A subsequent neurologic exam confirmed brain death and care was stopped.

Remember to adopt a step-wise approach to acid-base disorders to help delineate your work-up and treatment plan. Applying the “Rule of 15” and the “Delta Gap” formulas can help uncover hidden processes that one may miss at first glance of the patient’s laboratory data.