Hypocarbia

Acid-Base Physiology and Respiratory Control

• Hypocarbia (alternately: hypocapnia) is defined as a decrease in alveolar and blood carbon dioxide (CO₂) levels below 35 mmHg. There may be compensatory responses by the renal system.
• In an acute setting, the bicarbonate concentration decreases by 2 mEq/L for every 10 mmHg decrease in PaCO₂. In a chronic setting (after 3-5 days), the bicarbonate concentration decreases by 5 mEq/L for every 10 mmHg decrease in PaCO₂.
• Hypocarbia typically results in respiratory alkalosis. This can be a primary issue. More commonly, respiratory alkalosis occurs as a secondary effect of other conditions, such as hypoxemia or metabolic acidosis.¹
• Hypocarbia occurs when CO₂ elimination exceeds production. Renal compensation for acid-base disorders includes adjusting the amount of reabsorption of bicarbonate in the proximal tubule or bicarbonate production by the distal nephron to compensate for acidosis or alkalosis. In response to chronic hypocarbia, the kidney will produce less and reabsorb less bicarbonate.
• Changes in blood CO₂ levels alter cerebrospinal fluid (CSF) pH in the central nervous system, which, in turn, controls ventilation through multiple sets of receptors.
  • Central chemoreceptors, located in the medulla oblongata, adjust ventilatory rate based on CSF pH. Carotid bodies and aortic bodies stimulate respiratory drive, as well.
  • Peripheral chemoreceptors, similarly, sense changes in levels of hypoxemia. PaCO₂ (partial pressure of CO₂ in arterial blood) and alveolar ventilation are typically linearly related, meaning changes in CO₂ levels affect respiratory control.²
• Please see the OA summary “Pulmonary Ventilation: Physiology” for more details. Link
• Acute alkalosis increases the binding of calcium to albumin, resulting in reduced ionized calcium concentration without affecting total serum calcium levels. Acute alkalosis will shift potassium from plasma into cells, reducing plasma potassium concentration without affecting total body potassium levels. Temporary reductions in phosphate concentrations can occur due to binding with glucose in the context of alkalosis.³

Underlying Causes

• Hypocarbia may be directly due to a primary disorder or as a secondary effect to compensate for hypoxemia or metabolic acidosis. Iatrogenic hypocarbia can occur in patients receiving mechanical ventilation, which is occasionally used to temporize or treat specific conditions, as explained below.
• Primary causes of respiratory hypocarbia in awake patients include anxiety, pain, stress, or fear resulting in hyperventilation; head injury; fever; heatstroke; and hyperthyroidism.
• Hypoxemia can increase ventilatory drive and result in hyperventilation and secondary hypocarbia. Causes include extreme high altitude, pulmonary embolism, pneumothorax, pneumonia, pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease exacerbations.
• Metabolic acidosis of any type can result in compensatory hypocarbia in awake patients. This can include sepsis with lactic acidosis; ketoacidosis (from diabetes, starvation, alcohol or medication side-effects); toxic ingestions (methanol, ethylene glycol), medication toxicity (salicylate or theophylline); and renal or gastrointestinal losses (diarrhea, renal tubular acidosis, renal failure, ileal loop bladder).
• Relative hypocarbia also occurs during pregnancy. This is attributed to respiratory alkalosis compensated by renal bicarbonate excretion; refer to the OA summary “Physiologic Changes in Pregnancy.” Link

Relative Hypocarbia: Pregnancy

Clinical Significance and Management

• Hypocarbia has important physiological effects, some of which may have medical utility. Hypocarbia has important effects on oxygen binding and dissociation, cerebral blood flow, and pulmonary vascular resistance. When hypocarbia is a secondary effect, caused by another process, the physiological implications of that process must also be considered.

Symptoms of Hypocarbia

• Tachypnea is common in both acute and chronic hypocarbia, but is more pronounced in acute hypocarbia. Secondary hypocarbia due to hypoxemia may present with cerebral vasoconstriction and neural dysfunction. This can include paresthesia in the extremities, dizziness, confusion, seizures, and syncope. Sympathetic activation may result in sweating. Chronic hypocarbia may also lead to impaired vitamin D metabolism, hypocalcemia, with myalgias and tetany.^1,3 Decreased ionized calcium may manifest with Trousseau and Chvostek signs.

Oxygen Binding and Delivery

• Hypocarbia increases oxygen binding to hemoglobin through the Bohr effect. This results in reduced tissue delivery. This is also known as a leftward shift of the oxyhemoglobin dissociation curve. Please see the OA Summary “Oxygen Physiology” for more details. Link

Cerebral Effects

• Cerebral blood flow (CBF) is reduced by hypocarbia in a non-linear fashion. The cerebral blood volume (CBV) is 3-4 mL per 100 grams of parenchymal tissue. The changes in the cerebral vessel diameter may change the total CBV; nearly 70% of the total CBV corresponds to the venous system.
• Hypocarbia is used during craniotomy to reduce cerebral blood flow and volume, to relax the brain, and facilitate retraction and exposure. Hypocarbia can result in slowing of electroencephalogram waves, a pattern thought to reflect ischemia.
• The effects of hypocarbia on cerebral metabolic rate of oxygen (CMRO₂) are variable and heterogeneous, generally showing a decrease, but may cause neuronal excitement and an increase in CMRO₂.
• Hypocapnia may have variable effects on cerebral oxygenation. It can contribute to tissue hypoxia through different pathways:
  • Vasoconstriction and decreased CBF, leading to ischemic hypoxia
  • Leftward shift of the oxyhemoglobin dissociation curve, leading to impaired oxygen delivery
  • Increases in CMRO₂ in the context of reduced oxygen delivery (inconsistent/variable)
• As a result, in some patients cerebral oxygenation can decrease due to hyperventilation-induced hypocarbia, which is associated with worse patient outcome.³
• Hypocarbia should be avoided in patients with acute brain trauma and elevated intracranial pressure, except as a temporizing measure to address impending cerebral herniation. As hypocarbia reduces cerebral blood flow, this may worsen ongoing ischemia.
• Other treatment options are preferred and include hyperosmolar therapy, ensuring adequate sedation, and CSF drainage or decompressive craniotomy.
• Per the Brain Trauma Foundation guidelines, hypocarbia is typically contraindicated during the first 24 hours after trauma, except as a last resort with imminent life-threatening herniation.⁴
• Please see the OA Summary “Traumatic Brain Injury” for more details. Link

Pulmonary Vascular Effects

• Hypocarbia can reduce pulmonary arterial pressures, which is occasionally used to prevent or treat pulmonary hypertensive crisis in mechanically ventilated patients. However, this is used judiciously, as increased ventilator pressures to achieve hypocarbia may directly raise pulmonary arterial pressure, thereby reducing any putative benefit. The specific risk/benefit of hypocarbia in pulmonary hypertension needs to be individualized.

Systemic Effects

• Hypocarbia can reduce perfusion to various tissue beds, including the renal, GI, skin, and skeletal muscle beds. It reduces hypoxic pulmonary vasoconstriction and coronary blood flow and has been associated with coronary vasospasm. It can lead to increased anterior T-wave elevation. In animal studies, left ventricular performance was decreased by hypocapnia.
• Vasoactive factors that regulate the endothelium and vascular smooth muscle also react to pH changes – such factors include nitric oxide, prostaglandins, cyclic nucleotides, potassium, and calcium.³