Permissive Hypercapnia

Introduction¹

• Lung-protective ventilation strategies, particularly low tidal volumes used in the management of acute respiratory distress syndrome (ARDS) and asthma or chronic obstructive pulmonary disease (COPD) exacerbations, can lead to hypercapnia. Some degree of hypercapnia is tolerated to continue these ventilation strategies.
• The degree to which hypercapnia can be permitted is not constrained by an upper limit of PaCO₂, but by the rate of rise of PaCO₂ (generally less than 10 mmHg per hour) and by the lower limit of pH (generally ≥ 7.2).
• The etiologies, pathophysiology, and management of hypercapnia are discussed separately. See OA summary “Hypercarbia” for more details. Link

Indications

• ARDS using low tidal volume ventilation strategies (generally no more than 6cc/kg of the patient’s ideal body weight).
  • Maintaining low tidal volume ventilation through permissive hypercapnia is associated with lower barotrauma and ventilator-associated lung injury.²
  • See OA summary “Management of Patients with Acute Respiratory Distress Syndrome” for further details on ARDS management. Link
• Asthma or COPD exacerbations: using low tidal volume or low respiratory rate ventilation strategies.
  • In status asthmaticus and refractory asthma, the use of permissive hypercapnia to avoid high airway pressures, thereby limiting barotrauma and hypotension due to excess intrathoracic pressure, is associated with decreased mortality.^3,4
• Emergence: There is some evidence that mild hypercapnia may be beneficial for anesthetic emergence.
  • In one randomized trial, patients with mildly elevated end-tidal CO₂ (50–55 mmHg) experienced shortened extubation and voluntary eye-opening times after total intravenous anesthesia, without an increase in adverse effects.⁵
  • Similarly, in a meta-analysis, controlled mild hypercapnia was found to reduce the time to extubation and awakening without increasing adverse cardiopulmonary or neurologic events. However, there was significant heterogeneity across studies, and sample sizes were small; therefore, larger confirmatory interventional trials should be performed prior to routine clinical adoption.⁶

Contraindications and Associated Pathophysiology

• Acute hypercapnia induces systemic arteriolar vasodilation, especially in the cerebral and coronary vasculature. Acute hypercapnia can also transiently increase sympathetic tone, decrease cardiac contractility, and increase uterine contractility by interfering with myofilament response to calcium.
• Contraindications to permissive hypercapnia exist; therefore, in states in which acute vasodilation of these vascular beds, increased sympathomimetic output, or a change in contractility would worsen underlying pathologies.
• Acute cerebral disease: Cerebral vasodilation leads to increased intracranial pressure, worsening the effects of space-occupying lesions or other causes of intracranial hypertension.^1,3
  • The increase in intracranial pressure is usually transient, with cerebral blood flow returning to baseline around 48 hours of continuous hypercapnia.¹
  • Cerebral vasodilation due to hypercapnia results in cerebral edema in humans even in the absence of hypoxemia and generally reaches its maximum at PaCO₂ levels of about 120 mmHg.³
• Cardiac disease: Increased sympathetic tone can worsen many cardiac pathologies, such as coronary artery disease, heart failure, or arrhythmia. These pathologies are further worsened by the transient decrease in contractility caused by hypercapnia, and/or by coronary artery steal, which has been theorized to occur from hypercapnia but has not been confirmed in humans.^1,3
• Hypovolemia: As detailed above, hypercapnia can decrease cardiac contractility. In hypovolemic patients, an inability to compensate for low volumes with increased inotropy can precipitate cardiovascular collapse.³
• Pregnancy: Hypercapnia induces increased contractility of uterine smooth muscle and is therefore generally avoided in pregnant patients.¹

Technique

• The hallmark tenet of permissive hypercapnia is incremental change. Rapid changes in PaCO₂ should be avoided to prevent rapid changes in pH. There are no set guidelines; the following recommendations should be monitored clinically and with blood gas every 1-2 hours following changes in ventilation.¹
• Decrease minute ventilation:
  • Decrease respiration rate by up to 2 to 3 breaths per minute
    OR
  • Decrease tidal volumes by up to 25 – 50 mL
• Monitor the rate of change of PaCO₂
  • Increase in PaCO₂ should be less than 10 mmHg / hour
• Monitor pH, correct as needed
  • pH ≤ 7.2: correct with sodium bicarbonate to maintain a pH of at least 7.2
  • pH 7.21 – 7.24: consider sodium bicarbonate
  • pH ≥ 7.25: no change needed, generally well tolerated

Upper Limit of PaCO₂

• A large multicenter observational study found that, among critically ill patients, hypercapnia (PaCO₂ ≥ 45 mmHg) and severe hypercapnia (PaCO₂ ≥ 55 mmHg) are common, well-tolerated, and not associated with increased mortality.
• Prolonged hypercapnic acidosis and prolonged hypocapnia, on the other hand, were associated with increased mortality.⁷
• Case series have documented that, in the absence of contraindications such as cerebral or cardiac pathology, extreme hypercapnia, with a PaCO₂ as high as 150, can be tolerated for up to 16 hours to enable lung-protective ventilation in status asthmaticus.³
• Theoretically, in patients without contraindications to hypercapnia, there is no upper limit of PaCO₂ that can be tolerated as long as the PaCO₂ is reached incrementally and does not cause severe or uncompensated acidosis.