Respiratory arrest and cardiac arrest are distinct, but inevitably if untreated, one leads to the other. (See also Respiratory Failure, Dyspnea, and Hypoxia.)
Interruption of pulmonary gas exchange for > 5 minutes may irreversibly damage vital organs, especially the brain. Cardiac arrest almost always follows unless respiratory function is rapidly restored. However, aggressive ventilation may also have negative hemodynamic consequences, particularly in the periarrest period and in other circumstances when cardiac output is low. In most cases, the ultimate goal is to restore adequate ventilation and oxygenation without further compromising a tentative cardiovascular situation.
Etiology of Respiratory Arrest
Respiratory arrest (and impaired respiration that can progress to respiratory arrest) can be caused by
Airway obstruction
Decreased respiratory effort
Respiratory muscle weakness
Airway obstruction
Obstruction may involve the
Upper airway (above the vocal cords; ie, nasopharyngeal and oral cavities and larynx)
Lower airway (below the vocal cords; ie, trachea, bronchi, bronchioles, and alveoli)
Upper airway obstruction may be caused by any object or substance that blocks the oropharynx, including
Blood
Mucus
Vomitus
Foreign body
Spasm of the vocal cords
Edema of the vocal cords
Pharyngolaryngeal or tracheal inflammation (eg, epiglottitis, croup)
Posterior portion of the tongue in patients with decreased consciousness
Tumor
Trauma
In infants < 3 months, who are usually nose breathers, upper airway obstruction may occur due to nasal blockage.
Patients with congenital developmental disorders (eg, Down syndrome, laryngeal disorders, congenital jaw abnormalities) often have abnormal upper airways that are more easily obstructed. For example, patients who have Down syndrome commonly have an abnormal upper airway as a result of various anatomical characteristics, such as macroglossia or midfacial hypoplasia (1).
Lower airway obstruction may result from
Aspiration
Bronchospasm
Airspace filling disorders (eg, pneumonia, pulmonary edema, pulmonary hemorrhage)
Decreased respiratory effort
Decreased respiratory effort is caused by central nervous system (CNS) impairment due to one of the following:
CNS disorder
Adverse effect of medications or illicit drugs
Metabolic disorder
Obesity
Mechanical defects
CNS disorders that affect the brain stem (eg, stroke, infection, tumor) or cervical spine (eg, spinal cord injury) can cause hypoventilation (2, 3). Disorders that increase intracranial pressure usually cause hyperventilation initially, but hypoventilation may develop if the brain stem is compressed (4).
Medications that decrease respiratory effort include opioids and sedative-hypnotics (eg, barbiturates, alcohol, benzodiazepines). This decreased respiratory effort can also increase the dead space ventilation (expressed as dead space to tidal volume ratio [VD/VT]) and prolong liberation from mechanical ventilation for patients with a diminished tidal volume in a critical care setting or postoperatively (5).
Combinations of these medications further increase the risk of respiratory depression (6). Overdose (iatrogenic, intentional, or unintentional) of opioids or sedative-hypnotics typically causes respiratory depression, although a lower dose may decrease respiratory effort in patients who are more sensitive to the effects of these medications (eg, older adults, deconditioned patients, patients with chronic respiratory insufficiency or obstructive sleep apnea). Respiratory arrest due to illicit drug use, especially use of opioids (eg, heroin, fentanyl), is a common cause of out-of-hospital respiratory arrest. In hospitalized patients, the risk for opioid-induced respiratory depression (OIRD) is most common in the immediate postoperative recovery period but persists throughout a hospital stay and may affect almost 50% of postoperative patients (7). OIRD can lead to catastrophic outcomes such as severe brain damage or death (8).
sedatives), older adults, or patients who have underlying respiratory impairment such as patients with chronic obstructive pulmonary disease (COPD) (9).
Metabolic disorders that cause CNS depression due to severe hypoglycemia or hypotension ultimately compromise respiratory effort. For example, hypoglycemia may lead to a range of CNS effects, such as obtundation, or coma; confusion, or unusual behavior; and occasionally could manifest by dizziness, tremors, or seizures.
Obesity hypoventilation syndrome (OHS) is a condition that commonly occurs in patients with obesity and restrictive ventilatory defects (10). The exact cause is not known; however, research studies in rodent models suggest leptin mediated mechanisms. Leptin is a hormone essential for breathing regulation and may be related to changes in CO2 levels (11). OHS may result from excessive weight gain and leptin deficiency or resistance, leading to increased respiratory workload and reduced ventilation due to chemoreceptor blunting.
Mechanical defects or abnormalities in the chest wall (eg, kyphoscoliosis, extreme obesity) and respiratory muscle dysfunction (eg, due to phrenic nerve damage or neuromuscular disorders) can contribute to decreased respiratory effort and failure (5).
Respiratory muscle weakness
Weakness may be caused by
Respiratory muscle fatigue
Neuromuscular diseases
Corticosteroids or neuromuscular-blocking medications
Respiratory muscle fatigue can occur if patients breathe for extended periods at a minute ventilation exceeding about 70% of their maximum voluntary ventilation (eg, because of severe metabolic acidosis or hypoxemia) (5). Chronic respiratory disorders (eg, COPD) can result in respiratory muscle fatigue and dysfunction. In COPD, neuromuscular weakness can impact multiple muscle groups, including the chest wall, diaphragm, and peripheral muscles (12).
Neuromuscular causes, including spinal cord injury and neuromuscular diseases (eg, myasthenia gravis, botulism, poliomyelitis, Guillain-Barré syndrome), can cause respiratory muscle weakness (13).
In addition, bedrest combined with the use of , often used in critical care patients, can lead to respiratory muscle weakness (14, 15). Therefore, to minimize the potential risks of unfavorable outcomes (eg, ICU-associated muscle weakness, respiratory insufficiency, and hospital-acquired pneumonia (16), it is recommended to start physical therapy early and discontinue corticosteroids and/or neuromuscular-blocking medications as soon they are no longer needed.
Etiology references
1. Mitchell RB, Call E, Kelly J: Diagnosis and therapy for airway obstruction in children with Down syndrome. Arch Otolaryngol Head Neck Surg 129(6):642–645, 2003. doi:10.1001/archotol.129.6.642
2. Sankari A, Bascom A, Oomman S, Badr MS: Sleep disordered breathing in chronic spinal cord injury. J Clin Sleep Med 10(1):65–72, 2014. doi:10.5664/jcsm.3362
3. Bascom AT, Sankari A, Goshgarian HG, Badr MS: Sleep onset hypoventilation in chronic spinal cord injury. Physiol Rep 3(8):e12490, 2015. doi:10.14814/phy2.12490
4. Edlow JA, Rabinstein A, Traub SJ, Wijdicks EF: Diagnosis of reversible causes of coma. Lancet 384(9959):2064–2076, 2014. doi:10.1016/S0140-6736(13)62184-4
5. Roussos C: Respiratory muscle fatigue and ventilatory failure. Chest 97(3 Suppl):89S–96S, 1990. doi:10.1378/chest.97.3_supplement.89s
6. Izrailtyan I, Qiu J, Overdyk FJ, et al: Risk factors for cardiopulmonary and respiratory arrest in medical and surgical hospital patients on opioid analgesics and sedatives. PLoS One 13(3):e019455, 2018. doi: 10.1371/journal.pone.0194553
7. Khanna AK, Bergese SD, Jungquist CR, et al: Prediction of opioid-induced respiratory depression on inpatient wards using continuous capnography and oximetry: An international prospective, observational trial. Anesth Analg 131(4):1012–1024, 2020. doi:10.1213/ANE.0000000000004788
8. Lee LA, Caplan RA, Stephens LS, et al: Postoperative opioid-induced respiratory depression: A closed claims analysis. Anesthesiology 122: 659–665, 2015. doi: 10.1097/ALN.0000000000000564
10. Chau EH, Lam D, Wong J, Mokhlesi B, Chung F: Obesity hypoventilation syndrome: a review of epidemiology, pathophysiology, and perioperative considerations. Anesthesiology 117(1):188–205, 2012. doi:10.1097/ALN.0b013e31825add60
11. Amorim MR, Aung O, Mokhlesi B, Polotsky VY: Leptin-mediated neural targets in obesity hypoventilation syndrome. Sleep 45(9):zsac153, 2022. doi:10.1093/sleep/zsac153
12. Alter A, Aboussouan LS, Mireles-Cabodevila E: Neuromuscular weakness in chronic obstructive pulmonary disease: chest wall, diaphragm, and peripheral muscle contributions. Curr Opin Pulm Med 23(2):129–138, 2017. doi:10.1097/MCP.0000000000000360
13. Boentert M, Wenninger S, Sansone VA: Respiratory involvement in neuromuscular disorders. Curr Opin Neurol 30(5):529–537, 2017. doi:10.1097/WCO.0000000000000470
14. Eikermann M, Gerwig M, Hasselmann C, Fiedler G, Peters J: Impaired neuromuscular transmission after recovery of the train-of-four ratio. Acta Anaesthesiol Scand 51(2):226–234, 2007. doi:10.1111/j.1399-6576.2006.01228.x
15. Price DR, Mikkelsen ME, Umscheid CA, Armstrong EJ: Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical Illness: A Systematic Review and Meta-Analysis. Crit Care Med 44(11):2070–2078, 2016. doi:10.1097/CCM.0000000000001839
16. Fan E, Cheek F, Chlan L, et al: An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med 190(12):1437–1446, 2014. doi:10.1164/rccm.201411-2011ST
Symptoms and Signs of Respiratory Arrest
With respiratory arrest, patients are unconscious or will soon lose consciousness.
Respiratory arrest results in hypoxemia. Patients with hypoxemia may be cyanotic, but cyanosis can be masked by anemia, carbon monoxide poisoning, or cyanide toxicity. Because anemia lowers hemoglobin, reducing the total amount of deoxygenated hemoglobin when a patient is hypoxemic, cyanosis is not as apparent. Carboxyhemoglobin sometimes makes the skin appear red. In cyanide toxicity, patients may not appear cyanotic despite being functionally hypoxic because cyanide impairs cellular respiration. Cyanosis may also not be as apparent in patients with dark skin.
Patients being treated with high-flow oxygen may not be hypoxemic and therefore may not exhibit cyanosis or desaturation until after respiration ceases for several minutes. Conversely, patients with chronic lung disease and polycythemia may exhibit cyanosis without respiratory arrest.
If respiratory arrest remains uncorrected, cardiac arrest follows within minutes of onset of hypoxemia.
Impending respiratory arrest
Prior to respiratory arrest, patients may exhibit difficulty breathing, agitation, and confusion.
The respiratory rate in these patients may be increased or decreased, depending on the cause. For instance, upper airway obstruction or respiratory weakness may lead to tachypnea, whereas CNS etiologies (eg, intoxication, stroke) may result in decreased respiratory rate. Accurate assessment of respiratory rate is crucial in the early detection of respiratory decompensation, but routine methods (eg, nursing triage assessment, electronic monitors) are often inaccurate (1). Physicians should check on patients frequently to assess respiratory rate and effort and signs of impending respiratory arrest (eg, accessory muscle use for breathing, tripod positioning [patient leans forward with hands on knees]).
The characteristics of abnormal breath sounds or other findings on auscultation of the lungs can suggest an etiology or mechanism of respiratory failure:
Inspiratory stridor – Obstruction above the vocal cords (eg, foreign body, epiglottitis, angioedema)
Expiratory stridor or mixed inspiratory and expiratory stridor – Obstruction below the vocal cords (eg, croup, bacterial tracheitis, foreign body)
Wheezing – Bronchoconstriction, bronchospasm, or obstruction at the level of the bronchi and/or bronchioles (eg, asthma, anaphylaxis, a foreign body in a mainstem bronchus, a fixed lesion such as a tumor)
Lung crackles – Interalveolar fluid (eg, pneumonia, heart failure, pulmonary fibrosis); the absence of crackles does not rule out these disorders
Diminished breath sounds – Caused by conditions that prevent air from entering the lungs (eg, severe COPD, severe asthma, pneumothorax, tension pneumothorax, pleural effusion, hemothorax)
During the early stages of respiratory decompensation, accessory muscle use (eg, intercostal muscles, sternoclavicular muscles) is apparent. Patients with CNS impairment or respiratory muscle weakness exhibit feeble, gasping, or irregular respirations and paradoxical breathing movements. Patients with a foreign body in the airway may choke and point to their necks or show no symptoms.
Patients with asthma or with other chronic lung diseases may become hypercarbic and fatigued after prolonged periods of respiratory distress and suddenly become obtunded and apneic with little warning, despite adequate oxygen saturation. Therefore, careful monitoring and early intervention may prevent respiratory arrest (2).
Infants, especially if < 3 months, may develop acute apnea without warning, secondary to overwhelming infection, metabolic disorders, or respiratory fatigue.
Quantitative end-tidal carbon dioxide monitoring (ie, rising ETCO2 levels) can alert physicians and the healthcare team to the impending respiratory arrest.
Tachycardia and diaphoresis are commonly observed but not specific to respiratory arrest.
Symptoms and signs references
1. Lovett PB, Buchwald JM, Sturmann K, Bijur P: The vexatious vital: neither clinical measurements by nurses nor an electronic monitor provides accurate measurements of respiratory rate in triage. Ann Emerg Med 45(1):68–76, 2005. doi:10.1016/j.annemergmed.2004.06.016
2. Morris TA, Gay PC, MacIntyre NR, et al: Respiratory Compromise as a New Paradigm for the Care of Vulnerable Hospitalized Patients. Respir Care 62(4):497–512, 2017. doi:10.4187/respcare.05021
Diagnosis of Respiratory Arrest
Absence of respiration
Evaluation for cause based on history and physical examination, laboratory tests, imaging studies, and/or laryngoscopy
Respiratory arrest is clinically obvious because the patient is not breathing. It is an emergency, and treatment (eg, maintaining a basic or advanced airway and ventilatory support) begins immediately upon diagnosis. Care is typically provided by a team of clinicians, allowing for both resuscitative efforts and evaluation for etiology.
While resuscitation is performed, the patient is examined and history is obtained from any observers who were with the patient prior to the respiratory arrest (eg, observation of choking on a foreign body).
The first consideration is to exclude (or remove, if present) a foreign body obstructing the airway. A sign of a foreign body is marked resistance to ventilation during mouth-to-mask or bag-valve-mask ventilation. Foreign material may also be discovered during laryngoscopy for endotracheal intubation (see Clearing and Opening the Upper Airway).
Arterial blood gas measurements, complete blood count (CBC), electrolyte panel, lactate measurement, electrocardiogram, and chest radiograph are typically obtained to evaluate he cause of impending or established respiratory arrest. In addition, bedside ultrasound is an efficient method to investigate several significant causes (eg, pneumothorax, pulmonary edema, pneumonia) of respiratory failure (1).
Monitoring arterial oxygenation is crucial when evaluating patients with respiratory distress with pulse oximetry, which can demonstrate failing or inadequate oxygenation, but its accuracy can be affected by different conditions (eg, carbon monoxide poisoning, hyperbilirubinemia, dark skin [2]).
Diagnosis references
1. Lichtenstein DA, Mezière GA: Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol [published correction appears in Chest 2013 Aug;144(2):721]. Chest 134(1):117–125, 2008. doi:10.1378/chest.07-2800
2. Al-Halawani R, Charlton PH, Qassem M, Kyriacou PA: A review of the effect of skin pigmentation on pulse oximeter accuracy. Physiol Meas 44(5):05TR01, 2023. doi:10.1088/1361-6579/acd51a
Treatment of Respiratory Arrest
Clearing the airway, if obstructed
Mechanical ventilation
Treatment is clearing the airway (if obstructed), establishing an alternate airway, and providing mechanical ventilation as needed.
In an out-of-hospital environment, if a layperson finds a person unresponsive and the person has either absent or abnormal breathing, it is recommended that lay rescuers assume that the person is experiencing respiratory and cardiac arrest. Lay rescuers should promptly call for assistance from emergency services and initiate cardiopulmonary resuscitation (CPR) without delay (1). By focusing on these simple assessments—patient responsiveness and breathing assessment—lay rescuers can quickly initiate life-saving measures.
Treatment reference
1. Olasveengen TM, Mancini ME, Perkins GD, et al: Adult Basic Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 142(16_suppl_1):S41–S91, 2020. doi:10.1161/CIR.0000000000000892
