INTRODUCTION

Arterial blood gas (ABG) analysis is one of the crucial investigations which are most frequently employed in a critical care setting. A structured approach to rational interpretation of the ABG report requires a clear understanding of the basic concepts.

HISTORICAL ASPECTS

History of development of blood gas analysis and its application probably dates back to the pioneering work of anesthesiologist and researcher Dr John Severinghaus. In the 1950s, he developed the Stow–Severinghaus-type carbon dioxide electrode, which continues to be used for measurement of pCO₂ in blood gas machines today and the first-ever three-function (pH, pCO₂, and pO₂) blood gas analyzer (Fig. 1).

PURPOSE OF ARTERIAL BLOOD GAS

Arterial blood gas testing is widely used in emergency departments to evaluate the sick patients for metabolic disorders (acid–base disorders) and respiratory status, i.e., oxygenation and ventilation.

BACKGROUND

• The concept of pH was first put forward by the Danish chemist Soren Peter Sørensen 1909 to refer to the negative logarithm of hydrogen ion concentration (H⁺).
• The pH is a measurement of the acidity or alkalinity of the blood.
• The term “pH” stands for “Potential for Hydrogen”.
• Plasma pH of 7.40 corresponds to H⁺ ion concentration of 40 nEq/L.
• Plasma H⁺ ion concentration is inversely proportional to pH (Table 1).
  • In 1908, Lawrence Joseph Henderson wrote an equation describing the use of carbonic acid as a buffer solution.
  • Later, Karl Albert Hasselbalch re-expressed that formula in logarithmic terms, resulting in the so-called Henderson–Hasselbalch equation.

H⁺ (nEq/L) = 24 × [(PaCO₂/HCO₃)]

FIGS. 1A AND B: John W Severinghaus, MD, who invented modern blood gas analysis by combining electrodes for carbon dioxide, oxygen, and pH into one machine, died on June 2 at the age of 99 years.

COMPONENTS OF ARTERIAL BLOOD GAS

• pH (7.35–7.45) [Measurement of acidity or alkalinity, based on the hydrogen (H⁺) ions present]
• PaO₂ (80–100 mm Hg) (Partial pressure of oxygen that is dissolved in arterial blood)
• SaO₂ (95–100%) (Arterial oxygen saturation)
• PaCO₂ (35–45 mm Hg) (Amount of carbon dioxide dissolved in arterial blood)
• HCO₃ actual (22–28 mEq/L) (Actual bicarbonate: Plasma bicarbonate concentration, calculated from the actual pCO₂ and pH measurements)
• HCO₃ standard (22–28 mEq/L) (Standard bicarbonate: Plasma bicarbonate concentration calculated from the pCO₂ and pH measurements in the arterial blood sample after the pCO₂ is corrected)
• Base excess (BE; −2 to +2) (BE indicates the amount of excess or insufficient level of bicarbonate in the system)
• Na (135–145 mEq/L) (Plasma sodium concentration)
• K (3.5–5 mEq/L) (Plasma potassium concentration)
• Cl (95–105 mEq/L) (Plasma chloride concentration)
• Ca (1.0–1.25 mEq/L) (Plasma ionized calcium concentration)
• Lactate (0.4–1.4 mEq/L) (Lactate is produced as a by-product of anaerobic respiration. It is a good indicator of poor tissue perfusion.)
• Hemoglobin (Hb) (13–18 g/dL for men, 11.5–16 g/dL for women)

PHYSIOLOGICAL ASPECTS

Note: Gas molecules diffuse from higher partial pressures to lower partial pressures

• Alveolar oxygen (O₂) Pressure > Pulmonary capillaries
• Pulmonary capillary carbon dioxide (CO₂) Pressure > alveolar pressure

Hence,

• O₂ moves from alveoli into pulmonary capillaries (oxygenation)
• CO₂ diffuses from pulmonary capillaries into alveoli (ventilation)

TERMINOLOGY

• Type 1 respiratory impairment is defined by low PaO₂ with normal or low PaCO₂ due to inadequate oxygenation
  • With PaO₂ (mm Hg): Mild: 60–79, moderate: 40–59, severe: <40
  • Causes: Pneumonia, acute asthma, pulmonary embolism, acute respiratory distress syndrome (ARDS), pneumothorax, etc.

  It is better to explain it in terms of FiO₂ provided.

  Managed with treatment of the cause

  Support with mechanical ventilator, increase FiO₂

• Type 2 respiratory impairment is defined by high PaCO₂ (hypercapnia) > 45 mm Hg.
  • Acute rises in PaCO₂ lead to dangerous accumulation of acid in the blood and must be reversed earliest.
    • Cause: Acute hypoxia
  • Chronic hypercapnia is accompanied by a rise in the bicarbonate level, which preserves acid–base balance
    • Causes: Chronic obstructive pulmonary disease (COPD), opiate or benzodiazepine toxicity, inhaled foreign body, flail chest, neuromuscular disorders, obstructive sleep apnea

Note:

• Whenever there is a change in hydrogen ion concentration due to a change in PaCO₂, it is called respiratory acid–base disturbance.
  • With high PaCO₂, it is called respiratory acidosis.
  • With low PaCO₂, it is called respiratory alkalosis.
• Whenever there is a change in hydrogen ion concentration due to a change in HCO₃, it is called metabolic acid–base disorder.
  • With low HCO₃, it is called metabolic acidosis.
  • With high HCO₃, it is called metabolic alkalosis.
• Acidosis
  • When pH < 7.35 (due to increase in acid or decrease in alkali)
    • Metabolic acidosis: pH < 7.35 and HCO₃ < 22 mEq/L
    • Respiratory acidosis: pH < 7.35 and PaCO₂ > 45 mEq/L
• Alkalosis
  • When pH > 7.45 (due to decrease in acid or increase in alkali)
    • Metabolic alkalosis: pH > 7.45 and HCO₃ > 26 mEq/L
    • Respiratory alkalosis: pH > 7.45 and PaCO₂ < 35 mm Hg

Note: Alternatively, the nature of the acid–base disorder can be determined by using ABG nomogram (Fig. 2).

PHYSIOLOGICAL COMPENSATION

Compensation takes place by the buffering systems in the body.

FIG. 2: An alternative way of interpreting arterial blood gas (ABG) by utilizing ABG nomogram.

Source: Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J. Harrison’s Principles of Internal Medicine, 18th edition. New York: McGraw Hill; 2011.

    Compensatory Response to Simple/Primary Acid–Base Disorders

Refer to Table 2.

Note:

• During compensation, HCO₃ and PaCO₂ move in the same direction.
• If they move in the opposite direction, mixed acid–base disorder should be suspected.

FIG. 3: Male 45 years, acute respiratory distress syndrome (ARDS) with sepsis, metabolic acidosis. pH 7.286, PaO₂ 77.43, PaCO₂ 15.92, HCO₃ 7.22, BE 19.4 mmol/L, lactate 1.53, Cl 122.1 mmol/L.

Diagnosis: Mixed disorder: Metabolic acidosis and respiratory alkalosis
Type 1 respiratory failure

Mixed Acid–Base Disorders (Table 3; Figs. 3 to 7)

Mixed acid–base disorder is defined as independent coexistence of more than one primary acid–base disorder.

How to suspect mixed acid–base disorders?

• Mixed acid–base disorders occur in critically ill patients.
• Check the direction of changes, which take place in the opposite direction.

FIG. 4: Female 47 years, systemic lupus erythematosus (SLE), with lupus nephritis with dyspnea, metabolic acidosis + respiratory acidosis + treated with dialysis and mechanical ventilation. pH 7.119, PaCO₂ 19.3, PaO₂ 279.8 on FiO₂ 15 L, HCO₃ 6.1, BE 21.4 mEq/L.

Day 2: pH 7.228, PaO₂ 353 on ventilator, HCO₃ 11.8 mEq/L, BE 14.4 mEq/L, PaCO₂ 29.3
Diagnosis: Mixed acid–base disorder with metabolic acidosis and respiratory acidosis

FIG. 5: Female 24 years, ILD with ARDS, type 1 ARF with FiO₂ 60%, tidal volume 380 mL PEEP 5 cm, respiratory rate 16 breath/min, pH 7.358, PaCO₂ 53.40, PO₂ 95.21, VA/C mode, HCO₃ 27.01, BE 1.86 mEq/L.

Diagnosis: Acute respiratory acidosis with hypoventilation
(ARDS: acute respiratory distress syndrome; ARF acute respiratory failure; ILD: interstitial lung diseases)

FIG. 6: Female 52 years, diabetes mellitus, sepsis, nephropathy, hypoproteinemia, anion gap metabolic acidosis, with respiratory acidosis (mixed acid–base disorder, lactic acidosis) on continuous positive airway pressure (CPAP). pH 7.213, PaCO₂ 41.14, PaO₂ 140.5 at 50% FiO₂, SO₂ 98.82%, HCO₃ 14.62, Hb 11.9 g/dL, lactate 4.32, Na 140, K 3.9, blood urea 65 mg/dL, serum creatinine 3.6 mg, Blood sugar 208 mg/dL, albumin 2.2 g/dL, total leukocyte count (TLC) 16,6000/cmm, urine albumin ++, urine sugar +++, temperature 99.8^οC, BP 100/60 mm Hg, RR 26, PR 115, AG = 140 – (110.8 + 14.62) =15 mEq/L. In view of albumin 2.2 g/L, add 2.5 × 2 = 5 to AG. So, AG = 15 + 5 = 20.

Expected PaCO₂ = 14.62 + 15 = 29.62, but measured value = 41.14.
Diagnosis: Mixed acid–base disorder with metabolic acidosis and respiratory acidosis.

• Compare expected compensation with measured value. If the measured value is either high or low, suspect mixed acid–base disorder.
• Check the anion gap. In certain acid–base disorders, almost all values may be in the normal range. Only the anion gap will clinch the diagnosis of a mixed disorder.
• Physiological compensation does not take place in case of mixed acid–base disorders.

APPROACH FOR EVALUATION OF ARTERIAL BLOOD GAS

There are three important approaches for evaluation of acid–base disorders:

1. Physiological or Boston approach (developed by Schwartz and Relman from Boston)
2. Base excess or Copenhagen approach
3. Physicochemical or the strong ion approach/strong ion difference (SID)—Stewart’s approach

FIG. 7: Male 41 years, decompensated chronic liver disease, portal hypertension, right massive pleural effusion, pericardial effusion, acute kidney injury (AKI), hepatic encephalopathy. pH 7.45, PCO₂ 26.69 mm Hg, HCO₃ 15.81, BE −7.24 mEq/L

Measured PCO₂ is 26.69 mm Hg, lower than expected value.
Hence, mixed acid–base disturbance—metabolic acidosis and respiratory alkalosis.

    Clinical Approach

• Take targeted history in all critically ill patients followed by quick but meticulous clinical examination.
• Arterial blood sample to be taken, observing all precautions, preferably by observing modified Allen test, if acid–base disorder or respiratory impairment is suspected.
• To know the normal values of different components of ABG
• Validate the ABG report.
  • Analyze the ABG report and validate as below:
    • pH indirectly signifies hydrogen ion concentration
    • By the rule of thumb, if pH is 7.40, subtract the two numbers after 7 in the pH from 80, i.e., H⁺ = 80 − 40 = 40 (A).

    • H⁺ ion concentration = 24 × PaCO₂/HCO₃
    • Hence, H⁺ = 40 = 24 × 40/24 = 40 (B).
    • Compare the H⁺ by the two methods (validated if both results match).
  • Assess oxygenation and ventilation—PaO₂, SaO₂, PaCO₂
    • Look at PaO₂/FiO₂ ratio.
    • Normally, the ratio is 1:400–1:500.
    • If the ratio is < 1:300, consider ARDS.
    • Whether there is hypoventilation or hyperventilation by looking into PaCO₂
  • Look at pH, whether acidemia or alkalemia
  • Assess primary acid–base disorder (Flowchart 1)
  • Assess whether the disorder is acute or chronic; if the primary disorder is respiratory, consider the history of the patient.
  • Assess the compensatory response.
  • Determine whether there is any mixed acid–base disorder.

FLOWCHART 1: Primary acid–base disorders.

SOME IMPORTANT “ACID–BASE DISORDERS”

    Metabolic Acidosis

Metabolic acidosis is characterized by fall in plasma HCO₃ and fall in pH below 7.35. The PaCO₂ is secondarily reduced by hyperventilation, thus minimizing the fall in pH.

Mechanisms

• Loss of HCO₃ through kidney (type 2 renal tubular acidosis) or through gastrointestinal (GI) tract (diarrhea). Excess production of metabolic acids either by endogenous addition like DKA or by exogenous addition like silicate or ammonium chloride poisoning or decreased renal excretion like chronic kidney disease

Clinical Features

• Anorexia, nausea, vomiting, Kussmaul’s breathing, cardiac arrhythmias, hypotension, headache, confusion, and drowsiness
• May be normal anion gap or high anion gap—metabolic acidosis

Management

• Underlying primary cause to be treated
• IV fluids, insulin, and electrolyte replacement necessary for DKA
• Administration of sodium bicarbonate and/or dialysis in case acidosis associated with renal failure
• Restoration of an adequate intravascular volume and peripheral perfusion are necessary in lactic acidosis.

Note:

The following principles are to be adhered to:

• If pH is <7.15 or base excess is −12 or more, administer sodium bicarbonate as infusion.
• The goal is to keep pH between 7.1 and 7.15.
• Dose of sodium bicarbonate required depends on the volume of distribution of HCO₃.
• Between pH 7.3 and 7.4, distribution space is 50% of the lean body weight.
• Amount of HCO₃ required =

(Desired HCO₃ − actual HCO₃) × 0.5 body weight in kg

• If the pH is <7.1, volume of distribution is 100% of the lean body weight

(Desired HCO₃ − actual HCO₃) × body weight in kg

• 50% of the requirement has to be given in the first 24 hours, preferably as IV infusion but not as bolus
• The remaining dose is to be given considering the pH on the second day.

    Respiratory Acidosis

Respiratory acidosis is a clinical disorder characterized by an elevation in paCO₂ (hypercapnia) leading to reduction in pH and variable compensatory increase in the plasma HCO₃.

• It may be acute: With a duration of < 24 hours or chronic > 24 hours

Mechanisms

Airway obstruction, pulmonary disease, muscle fatigue, or abnormality in ventilator control

Clinical Features

• Those of the underlying cause and those due to hypercapnia
• Acute severe respiratory acidosis may cause anxiety, headache, dyspnea, confusion, psychosis, hallucination, and coma.
• Mild-to-moderate chronic hypercapnia may cause sleep disturbances, loss of memory, personality changes, tremor, and myoclonic jerks.

Treatment

• Treatment varies as per the severity, rate of onset, and underlying etiology.
• Acute hypercapnia: Mechanical ventilatory support; increase the positive end-expiratory pressure (PEEP), FiO₂, tidal volume, and set respiratory rate in order to keep the airways and alveoli patent.
• Target PaCO₂ level would be 40 mm Hg.
• Chronic hypercapnia O₂ therapy should be administered cautiously, aiming for the lowest possible concentration, with the target PaCO₂ level being lower than the previously stable value.

Note:

• Avoid alkali therapy except in patients with associated metabolic acidosis or severe acidosis (pH < 7.15) or severe bronchospasm.

Metabolic Alkalosis

• The primary abnormality in the bicarbonate buffering system is a rise in HCO₃.
• There is little compensatory change in PaCO₂.
• It is less common than metabolic acidosis.
• It is characterized by increase in plasma bicarbonate, rise in pH, and small compensatory rise in PaCO₂.

Causes

• Vomiting or gastric aspiration, diuretic use (thiazides, furosemide), hypokalemia, primary and secondary hyperaldosteronism, administration of exogenous alkali

Clinical Features

• Acute alkalosis may cause tetany, confusion, and drowsiness.

Treatment

• Treatment of the underlying cause in saline responsive alkalosis
• IV isotonic saline with KCl or Isolyte G are preferred infusions.
• Avoid H₂ receptor inhibitors, proton-pump inhibitors, and exogenous alkali.
• Dialysis may be helpful in occasional patients with severe metabolic alkalosis.

    Respiratory Alkalosis

It is characterized by low PaCO₂ (<35 mm Hg) and (high pH > 7.45) and compensatory low HCO₃.

Etiology

• Normal pregnancy, high altitude residence
• Anxiety- or pain-induced hyperventilation
• Sepsis or hepatic failure or brain tumor
• Excessive mechanical ventilator support

Clinical Features

• They vary with severity, rate of onset, and underlying disorders.
• Light headache, tingling of the extremities, circumoral numbness, cardiac arrhythmias, rarely seizures.

Treatment

• Vigorous treatment of the underlying cause
• O₂ supplementation to combat hypoxemia
• Reassurance and rebreathing into paper bag if the cause is psychogenic
• Pretreatment with acetazolamide minimizes symptoms due to hyperventilation at high altitude

CONCLUSION

Respiratory impairment or acid–base disturbances can occusr in different clinical settings, such as obstetric practice, intraoperative or postoperative conditions, road traffic accidents, sepsis, or many critically ill patients in the intensive care unit (ICU). Hence, a high index of clinical suspicion is required to predict the proper clinical condition and ABG should be ordered as early as possible and carefully analyzed and managed accordingly.

SUGGESTED READINGS

1.   Severinghaus JW. Gadgeteeriing for health care. Anaesthesiology. 2009;110:721-8.

2.   Sorensen SPL. Enzyme studies II. The measurement and meaning of hydrogen ion concentration in enzymatic processes. Biochemishe Zeitschrift. 1909;21:131-200

3.   Encyclopedia Britannica. [online] “Henderson–Hasselbalch equation” biochemistry. Available from https://www.britannica.com/science/Henderson-Hasselbach-equation [Last accessed January, 2024].

4.   Acid–Base Tutorial. Acid–base tutorial—history. [online] “Henderson–Hasselbalch equation” biochemistry. Available from [Last accessed January, 2024].

5.   Muller-Plathe O. A monogram for the interpretation of acid-base data. J Clin chem. Clin Biochem. 1987;25(11):795-8.

6.   Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol. 2010;6:274-85.