Hypercapnia is the elevation in the partial pressure of carbon dioxide (PaCO2) above 45 mm Hg. Carbon dioxide (CO2) is a metabolic product of the many cellular processes within the body to process lipids, carbohydrates, and proteins. There are a host of physiological mechanisms present which are responsible for the moderation of CO2 levels. These include the pH buffering system between hydrogen carbonate (HCO3) and CO2. Due to this relationship, hypercapnia leads to acid-base imbalance abnormalities.
At its root, hypercapnia is caused by either increased CO2 production metabolically or Respiratory failure. Metabolic processes that increase CO2 production may include fever, thyrotoxicosis, increased catabolism seen in sepsis or steroid use, overfeeding, metabolic acidosis, and exercise. Respiratory failure in this pathology is a failure to eliminate CO2 from the pulmonary system, which is synonymous with hypoventilation secondary to decreased respiratory rate or decreased tidal volume. This is from decreased central nervous system respiratory drive, anatomical defects, decreased neuromuscular response, or increased dead space within the lung. It is also technically possible to develop hypercapnia through exposure and inhalation of environmental air rich in CO2. Depending on the etiology, hypercapnia can be an acute process or a chronic process. These can be distinguished through evaluation of the pH. Acute hypercapnia will have PaCO2 elevated above the normal reference range of 45 mm Hg, and the HCO3 level will be within normal limits at approximately 30 mm Hg with a resulting proportional decrease in pH on blood gas evaluation below 7.35. Chronic hypercapnia allows for renal compensation to the elevated CO2 levels within the blood. As a result, PaCO2 will be elevated above the normal reference range of 45 mm Hg and the HCO3 level will also be elevated proportionally resulting in a less severe pH imbalance in the low-normal range. It is also to have an acute-on-chronic etiology that creates a combined picture with elevated PaCO2 and elevated HCO3 with an abnormal, decreased pH below 7.35.
Hypercapnia is a syndrome of illness rather than a single disease etiology. As such the exact epidemiology is linked to the specific inducing pathology.
One of the purposes of the pulmonary system is to remove CO2 from the body through gas diffusion. This requires a diffusion gradient from the high concentration arteriolar blood into the relatively low concentration environmental air. As such, the CO2 gradients are developed and maintained where PaCO2 in arterial blood is directly proportional to the rate of CO2 metabolic production and inversely related to the rate of CO2 elimination by the lung via increased alveolar ventilation. Alveolar ventilation is the removal of alveolar air into the environment, defined as the expired minute volume that reaches the alveoli and is determined by minute ventilation and the ratio of dead space to tidal volume. The human body is very adapted and capable of eliminating CO2 from the body as excesses are produced. Essentially, unless there is a significant loss of pulmonary ventilation metabolic processes will not induce hypercapnia.  Mathematically, this relationship is determined as:
PaCO2 = 0.863 x VCO2/ VA
VA = VE – VD
VE = RR x TV
TV = RR x dead-space volume
Where VCO2 is the metabolic production of CO2, VA is alveolar ventilation, VE is minute ventilation, VD is dead space ventilation, RR is the respiratory rate, and TV is tidal volume.
These relationships indicate that respiratory rate and tidal volume are the two components of ventilation that are physiologically or artificially controlled to moderate CO2 elimination. Therefore, a failure in either of these fields will induce hypercapnia. It is important also to note that as PACO2 increases, oxygenation decreases. This is explained using the alveolar gas equation:
PaO2 = FiO2 (Patm – PH2O) – PaCO2 / R
Where FiO2 is the fraction of inspired oxygen (0.21 at room air), Patm is atmospheric pressure (760 mm Hg), PH20 (47 mm Hg), PaCO2 as calculated from the arterial blood gas, and R (0.8 standard value).
The exact history and physical findings are highly variable depending on the source of hypercapnia. Patients may present with a complaint of flushed skin, lethargy, inability to focus, mild headaches, disorientation, dizziness, shortness of breath, dyspnea on exertion, nausea, vomiting, and/or fatigue. More severe complaints include confusion, paranoia, depression, abnormal muscle twitches, palpitations, hyperventilation or hypoventilation, seizures, anxiety, and/or syncope. Often, if a patient has a known history of asthma or chronic obstructive pulmonary disease (COPD), they will know the symptoms of exacerbation and present with this as the primary complaint.
Physical exam findings are typically vague but may indicate an underlying disease. These may include fever, obesity, tachycardia, tachypnea, dyspnea, altered mental status, wheezing on auscultation, rales on auscultation, rhonchi on auscultation, decreased breath sounds, hyper-resonant chest on percussion, increased anterior-posterior diameter of chest, cardiac murmur, signs of hypoxia may be present, hepatosplenomegaly, neurological deficit, confusion, somnolence, muscular weakness, peripheral edema, asterixis, papilledema, superficial vein dilation, and/or obesity.
An evaluation of hypercapnia needs to follow clinical suspicion, as the differential diagnostic list is long. Essential tests to consider in most patients include:
Treatment of hypercapnia should target the underlying pathology. Direct interventions exist to assist in CO2 removal by supplementing ventilation of the lungs. These include Bi-level Positive Airway Pressure (BiPAP) ventilation assist, Continuous Positive Airway Pressure (CPAP) ventilation, and intubation with mechanical ventilation in severely ill patients. BiPAP is typically preferred in an alert, awake patient who can protect his or her airway as it allows for better air exchange between the alveolar space and atmospheric air by providing alternating levels of positive pressure support to the airway. CPAP is used in patients where there is a need for airway splinting. However, this is inferior for CO2 exchange compared to BiPAP. While technically non-invasive, these treatments are poorly tolerated due to discomfort by many patients and function as a bridging therapy to recover without more invasive measures. Mechanical ventilation is the most invasive of the listed options, but it allows the physician better control of both respiratory rate and tidal volume in addition to FiO2 and pressure support. If a patient is not alert, awake, or able to protect their airway, mechanical ventilation should be strongly considered. BiPAP, CPAP, and intubation are not curative treatments on their own, but they are supportive as stabilizing measurements while the underlying etiology is corrected. Regardless of which support is used, it is essential to optimize oxygenation status maintaining O2 saturation 90% or higher.
There is a myriad of disease pathologies that lead to hypercapnia. These include:
Hypercapnia has a variable prognosis dependent on the exact inducing etiology. In general, younger patients have a better prognosis than older patients.
The pulmonary system is typically excellent at removing excess CO2 from the body. Most causes of hypercapnia are due to the failure of the pulmonary system to ventilate properly removing CO2.
BiPAP, CPAP, and intubation with mechanical ventilation are supportive measures that aim to optimize oxygenation while removing CO2 from the body, but the treatment of hypercapnia should focus on identifying the inducing etiology and target therapy towards it. Often, there is more than one insulting disease present.
The management of hypercapnia is made with than interprofessional team that includes ICU nurses. The key is to treat the primary condition causing hypercapnia. All the underlying electrolyte and metabolic deficits need to be corrected. The prognosis depends on the cause.
|||Sleep architecture in Pierre-Robin sequence: The effect of mandibular distraction osteogenesis., Bangiyev JN,Traboulsi H,Abdulhamid I,Rozzelle A,Thottam PJ,, International journal of pediatric otorhinolaryngology, 2016 Oct [PubMed PMID: 27619032]|
|||Fernando SM,Charbonneau V,Rosenberg H, Hypercapnea and Acidemia despite Hyperventilation following Endotracheal Intubation in a Case of Unknown Severe Salicylate Poisoning. Case reports in critical care. 2017; [PubMed PMID: 28465843]|
|||Hypercapnia., Weinberger SE,Schwartzstein RM,Weiss JW,, The New England journal of medicine, 1989 Nov 2 [PubMed PMID: 2677729]|
|||Central sleep apnea: Pathophysiology and treatment., Eckert DJ,Jordan AS,Merchia P,Malhotra A,, Chest, 2007 Feb [PubMed PMID: 17296668]|
|||Causes of carbon dioxide retention in lung disease., West JB,, The New England journal of medicine, 1971 Jun 3 [PubMed PMID: 5573833]|
|||Physiology, Pulmonary, Brinkman JE,Sharma S,,, 2018 Jan [PubMed PMID: 29494033]|
|||Congenital diaphragmatic hernia - the past 25 (or so) years., Lally KP,, Journal of pediatric surgery, 2016 May [PubMed PMID: 26926207]|
|||Physiology, Alkalosis, Respiratory, Brinkman JE,Sharma S,,, 2018 Jan [PubMed PMID: 29489286]|
|||Ventilatory failure. Etiology and clinical forms., Williams MH Jr,Shim CS,, The American journal of medicine, 1970 Apr [PubMed PMID: 5444303]|
|||Pattern of breathing and carbon dioxide retention in chronic obstructive lung disease., Javaheri S,Blum J,Kazemi H,, The American journal of medicine, 1981 Aug [PubMed PMID: 6789677]|
|||Hopkins E,Sharma S, Physiology, Acid Base Balance 2019 Jan; [PubMed PMID: 29939584]|
|||Sharma S,Rawat D, Hypocarbia 2018 Jan; [PubMed PMID: 29630219]|
|||Alveolar Gas Equation, Sharma S,Burns B,,, 2018 Jan [PubMed PMID: 29489223]|
|||Castro D,Keenaghan M, Arterial Blood Gas 2019 Jan; [PubMed PMID: 30725604]|
|||Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease., Aubier M,Murciano D,Fournier M,Milic-Emili J,Pariente R,Derenne JP,, The American review of respiratory disease, 1980 Aug [PubMed PMID: 6774639]|
|||Recent advances in obesity hypoventilation syndrome., Mokhlesi B,Tulaimat A,, Chest, 2007 Oct [PubMed PMID: 17934118]|
|||Mechanisms of activity-related dyspnea in pulmonary diseases., O'Donnell DE,Ora J,Webb KA,Laveneziana P,Jensen D,, Respiratory physiology & neurobiology, 2009 May 30 [PubMed PMID: 19450767]|
|||Treatment of Sleep Disordered Breathing Liberates Obese Hypoxemic Patients from Oxygen., Povitz M,Hanly PJ,Pendharkar SR,James MT,Tsai WH,, PloS one, 2015 [PubMed PMID: 26451835]|
|||Hypoventilation syndromes., Piper AJ,Yee BJ,, Comprehensive Physiology, 2014 Oct [PubMed PMID: 25428856]|
|||Hypoxemia, hypercapnia, and breathing pattern in patients with chronic obstructive pulmonary disease., Parot S,Miara B,Milic-Emili J,Gautier H,, The American review of respiratory disease, 1982 Nov [PubMed PMID: 7149454]|
|||Physiology, Acidosis, Respiratory, Patel S,Sharma S,,, 2018 Jan [PubMed PMID: 29494037]|
|||Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure., Aubier M,Murciano D,Milic-Emili J,Touaty E,Daghfous J,Pariente R,Derenne JP,, The American review of respiratory disease, 1980 Nov [PubMed PMID: 6778278]|
|||Control of breathing in patients with chronic obstructive lung disease., Sorli J,Grassino A,Lorange G,Milic-Emili J,, Clinical science and molecular medicine, 1978 Mar [PubMed PMID: 630805]|
|||Chronic respiratory failure in patients with neuromuscular diseases: diagnosis and treatment., Paschoal IA,Villalba Wde O,Pereira MC,, Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia, 2007 Jan-Feb [PubMed PMID: 17568873]|