Awake Acute Blood Loss: Acid-Base Disorders

Introduction

• In states of acute blood loss, typically manifesting as hemorrhagic shock, the human body employs several protective mechanisms to maintain homeostasis.^1,2 This includes peripheral vasoconstriction and shunting of blood to vital organs, tachycardia, tachypnea, and diaphoresis.
• During these compensatory behaviors, the body’s acid-base balance can be shifted from baseline. If blood loss is too rapid or substantial in volume, the compensatory mechanisms that maintain the body’s pH will eventually become exhausted, leading to a decompensated state. The goal of care for this acute blood loss is to prevent irreversible decompensation.

Basics of Acid-Base Physiology

• During states of metabolic acidosis or alkalosis, the body will use respiratory compensation, where the expected compensation can be calculated using Winter’s formula: Expected PCO₂ = (HCO3 x 1.5) + 8 ± 2.³
• During states of respiratory acidosis or alkalosis, the kidneys compensate by regulating hydrogen ion and bicarbonate levels. This compensation can be calculated using the following formulas:

Expected Compensation for Respiratory Acid-Base Disorders³

Awake Acute Blood Loss Physiology

Acid-base disturbances in awake acute blood loss can be divided into three phases:

1. The initial acid-base disturbance in acute blood loss is characterized by compensatory respiratory alkalosis, usually occurring from a volume loss of around 15-30%, 750 mL to 1500 mL4. This occurs due to decreased blood volume, which reduces venous return to the heart and thereby decreases stroke volume. This decrease in stroke volume activates baroreceptors in the carotid body and aortic arch, thereby increasing sympathetic nervous system activity (Figure 1).
   Hyperventilation increases the amount of CO₂ expired, lowering the PaCO₂ and raising the blood pH above 7.45. With persistent hyperventilation, metabolic compensation will follow, lowering bicarbonate levels through mechanisms such as increased urinary excretion.^4-6

2. The second phase is characterized by respiratory alkalosis in the setting of metabolic acidosis. In this phase, there is progressive decompensation from continued blood loss. This blood loss leads to tissue hypoxia, forcing cells to revert to anaerobic respiration.⁴ As a result of anaerobic respiration, lactic acid is produced, causing metabolic acidosis, along with respiratory alkalosis due to continued tachypnea. Because of concurrent metabolic acidosis in the setting of respiratory alkalosis, the pH may appear normal, but the CO₂ and bicarbonate levels will be low. During this period, the body’s compensatory mechanisms remain in play; however, as blood loss continues, decompensation occurs.^4-7

3. Irreversible decompensation of metabolic regulation in the setting of metabolic acidosis characterizes the late phase of acute blood loss acid-base balance. As severe hypotension and blood loss develop, organ perfusion declines, and lactate levels continue to rise. Respiratory failure ensues from increased work by the respiratory muscles, reduced blood flow to vital organs such as the lungs, hypoxemia, and hypercarbia.⁸ As respiratory fatigue develops, there is decreased ability for the lungs to compensate, resulting in respiratory acidosis from decreased expiration of CO₂. In concurrence with this, the kidneys, which are highly sensitive to changes in blood oxygen levels, begin to experience reduced compensation due to reduced perfusion. In combination, these decompensations cause elevated lactic acid, low bicarbonate, and respiratory acidosis due to exhaustion of the respiratory drive. This state of severe acidosis (pH ≤ 7.2) induces detrimental peripheral vasoconstriction, worsens the hemodynamic response, promotes cell apoptosis, and, ultimately, leads to death.^4-7

Management

• Management of acute blood loss depends on the stage and severity of the acid-base imbalance. The degree of blood loss is classified into 4 phases that help guide treatment decisions:⁴
  • Class 1 involves up to 15% total blood loss;
  • Class 2 is 15-30% blood loss with symptoms such as tachypnea, tachycardia, and hypotension;
  • Class 3 is 30-40% blood loss marked by severe hypovolemia and mental status change;
  • Class 4 is greater than 40% blood loss and is characterized by severe decompensation.
• Oxygen support and fluid resuscitation are the top priorities for increasing fluid volume and preventing pulmonary hypertension in the setting of acute blood loss,⁷ as acid-base imbalances can occur as early as 15% blood loss.
• These therapies include fluid resuscitation, oxygen administration, invasive mechanical ventilation (if necessary), correction of acidemia, vasopressors in the case of severe blood loss leading to hemorrhagic shock, and massive transfusion protocol.
• Oxygenation: Invasive mechanical ventilation reduces the oxygen demand of the respiratory muscles and decreases left ventricular afterload. In addition, the end-tidal CO₂-to-PaCO₂ ratio should be used to guide minute ventilation to avoid hypoventilation.⁷
• Fluid Management:
  • To manage severe acidosis with a pH less than 7.1, intravenous sodium bicarbonate is considered. Still, its use remains controversial.² If intravenous bicarbonate is administered, it must be infused slowly with proper ventilation and calcium replacement to mitigate its negative effect on cardiac contractility.⁹
  • Renal replacement therapy can also be initiated if pH is below 7.15 in the absence of severe respiratory acidosis.²
  • Massive blood loss usually requires massive transfusion protocol, characterized by rapid blood component delivery and administration10. This transfusion usually involves 10 or more units of red blood cells or whole blood within 24 hours, while ultra-massive transfusion involves 20 or more units in 24-48 hours.¹⁰ Please see the OA summary on massive hemorrhage protocol for more details. Link
• Vasopressors: Vasopressors are indicated if hypotension persists despite fluid resuscitation, with norepinephrine being the first choice.⁷ Epinephrine, although it exerts stronger effects, is associated with a higher incidence of arrhythmias. Inotropic agents such as dobutamine, phosphodiesterase type III inhibitors, and levosimendan may also be utilized to increase cardiac output.⁷ It is important to note that vasopressors should only be used as a temporizing measure, as prolonged use can lead to tissue ischemia and organ damage. Please see the OA summary on vasopressors and inotropes for more details. Link
• Acute blood loss triggers a sequence of acid-base disturbances that can be categorized into three phases, ranging from respiratory alkalosis to decompensated mixed acidosis. Understanding these phases is critical for treatment intervention, which mainly relies on resuscitation through oxygenation, fluid replacement, and RBC transfusion.