Hypoventilation

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Hypoventilation
ICD-10 R06.8
DiseasesDB 29214
MeSH D007040

For patient information, click Hypoventilation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Amresh Kumar MD [2]

Synonyms and keywords:

Overview

In medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo means "below") to perform needed gas exchange. It generally causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. It can be caused by medical conditions, by holding one's breath, or by drugs, typically when taken in overdose. Hypoventilation may be dangerous for those with sleep apnea.

Classification

Pathophysiology

Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo meaning "below") to perform needed gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis.

Associated Conditions

  • Disorders like (CCHS) and Rapid-Onset Obesity, Hypothalamic Dysfunction, Hypoventilation, with Autonomic Dysregulation are recognized as conditions that are associated with hypoventilation. CCHS may be a significant factor in some cases of (SIDS), often termed "cot death" or "crib death".
  • The opposite condition is (too much ventilation), resulting in low carbon dioxide levels, rather than hypercapnia.

Causes

Life Threatening Causes

Common Causes

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning No underlying causes
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect Acetaminophen/Codeine Phosphate, Acetaminophen/Oxycodone Hydrochloride, Alcuronium, Alfentanyl, Alfentanil Hydrochloride, Alprostadil, Amobarbital sodium, Apomorphine, Aspirin/Caffeine/Dihydrocodeine Bitartrate, Aspirin/Codeine Phosphate, Aspirin/Oxycodone Hydrochloride, Atropine Sulfate, Baclofen, Brimonidine, Bupivacaine, Buprenorphine, Buprenorphine Hydrochloride, Buprenorphine/Naloxone, Butalbital/Acetaminophen/Caffeine/Codeine Phosphate, Butalbital/Aspirin/Caffeine/Codeine Phosphate, Butorphanol, Butorphanol Tartrate, Carisoprodol/Aspirin/Codeine Phosphate, Cifenline, Clobazam, Clonazepam, Clonidine, Codeine, Codeine Phosphate/Guaifenesin, Codeine Sulfate, Dantrolene, Desflurane, Dexmedetomidine, Dexmedetomidine Hydrochloride, Diazepam, Diclofenac, Dihydrocodeine, Disulfiram, Droperidol, Enflurane, Ethanol, Fentanyl, Fentanyl Citrate, Fentanyl/Droperidol, Halazepam, Homatropine Methylbromide/Hydrocodone Bitartrate, Hydrocodone, Hydrocodone Bitartrate, Hydrocodone Bitartrate/Acetaminophen, Hydrocodone Bitartrate/Chlorpheniramine Maleate, Hydrocodone Bitartrate/Guaifenesin, Hydrocodone Bitartrate/Ibuprofen, Hydrocodone Bitartrate/Pseudoephedrine Hydrochloride, Hydrocodone Polistirex/Chlorpheniramine Polistirex, Hydrocodone/Chlorpheniramine/Pseudoephedrine, Hydromorphone, Hydromorphone Hydrochloride, Ipratropium, Isoflurane, Ketamine, Ketamine Hydrochloride, Levorphanol, Levorphanol Tartrate, Lidocaine, Lopinavir/Ritonavir, Lorazepam, Magnesium, Meperidine, Meperidine Hydrochloride, Methadone, Methadone Hydrochloride, Methohexital, Methohexital Sodium, Midazolam, Midazolam Hydrochloride, Morphine, Morphine Sulfate, Morphine Sulfate Liposome, Morphine Sulfate/Naltrexone Hydrochloride, Nalbuphine, Nalbuphine Hydrochloride, Nefopam, Neostigmine, Nortriptyline, Onabotulinumtoxina, Opium, Oxaprozin, Oxycodone, Oxycodone Hydrochloride, Oxycodone Hydrochloride/Naloxone Hydrochloride, Oxycodon, Oxycodone Hydrochloride, Oxycodone Hydrochloride/Naloxone Hydrochloride, Oxycodone/Ibuprofen, Oxymorphone, Oxymorphone Hydrochloride, Paregoric, Pancuronium, Pancuronium Bromide, Pentazocine, Pentazocine Hydrochloride/Acetaminophen, Pentazocine Hydrochloride/Naloxone Hydrochloride, Pentazocine Lactate, Pentobarbital, Phenelzine, Polymixinb, Prilocaine, Prilocaine Hydrochloride, Promethazine, Promethazine Hydrochloride, Promethazine Hydrochloride/Codeine Phosphate, Promethazine/Phenylephrine/Codeine Phosphate, Propoxyphene, Propoxyphene Napsylate/Acetaminophen, Quinine, Remifentail, Remifentanil Hydrochloride, Riluzole, Rimabotulinumtoxinb, Secobarbital sodium, Sevoflurane, Sodium Oxybate, Succinylcholine, Succinylcholine Chloride, Sufentanil, Sufentanil Citrate, Tapentadol, Tapentadol Hydrochloride, Thiopental Sodium, Tilidine, Tramadol, Tramadol Hydrochloride, Tromethamine, Zanamivir
Ear Nose Throat No underlying causes
Endocrine No underlying causes
Environmental No underlying causes
Gastroenterologic No underlying causes
Genetic No underlying causes
Hematologic No underlying causes
Iatrogenic No underlying causes
Infectious Disease No underlying causes
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic No underlying causes
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte No underlying causes
Rheumatology/Immunology/Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous No underlying causes

Differentiating hypoventilation from other Diseases

Abbreviations: Ab (antibody); ABG (arterial blood gas); BMP (basic metabolic panel); BPS (biophysical profile score); CHS (central hypoventilation syndrome); CBC (complete blood count); CPK (Creatine phosphokinase); CSF (cerebrospinal fluid); CT (computed tomography ); CXR (chest X-ray); DMD (dystrophin gene);  ECG (electrocardiogram); EMG (electromyography); FEF (forced expiratory flow rate); FEV1 (forced expiratory volume); FRC (functional residual capacity); FVC (forced vital capacity); GIT (gastrointestinal tract); JVD (jugular vein distention); MAS (meconium aspiration syndrome); MCV (mean corpuscular volume); MRI (magnetic resonance imaging); NCS (Nerve conduction studies); PEF (pulmonary expiratory flow); RDS (acute respiratory distress syndrome); ROHHAD (rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation); RV (residual volume); SIRS (systemic inflammatory response syndrome); SMN1 (survival of motor neuron 1); TLC (total lung capacity) TSH (thyroid stimulating hormone); Vt (tidal volume); WBC (white blood cell);

Diseases Clinical manifestations Diagnosis Associated features
Symptoms Physical exam
Chest pain Dyspnea Orthopnea Fever Palpitations Poor

quality sleep

Cyanosis JVD Peripheral edema Auscultation ABGs Lab findings Imaging Spirometry Gold standard
Central hypoventilation syndrome CHS[1][2][3] - + + - +/- + + +/- +/-
  • Normal
 ↓O2, ↑CO2 Normal
Asphyxia[4][5][6] - + +/- - +/- + + +/- +/- ↓O2, ↑CO2 Normal
Chiari II malformation (Arnold-Chiari)[7][8][9] - + + - + + - - - Normal _ _ MRI Brain
Spinal muscular atrophy[10][11][12] - + + - +/- + + - - _ _ _ Molecular genetic testing  by detection of homozygous deletions of exons 7 of the SMN1 gene
Guillain-Barré syndrome[13][14][15] - + +/- - + +/- - - - ↓O2, ↑CO2 ↓FEV1

↓FVC

↓TLC

Phrenic nerve injury[16][17][18] +/- + + +/- - +/- - - -
  • Normal
 Normal ↓Vt, ↑RV

(anatomical)

  • Fluoroscopic "sniff" test (diaphragmatic movement is observed fluoroscopically while the patient sniffs forcefully)
Myasthenia gravis[19][20][21] - + +/- - - + - - - ↓O2, ↑CO2
  • Anti-AChR ab
  • Anti–striated muscle ab
  • Anti-MuSK ab
 ↓FEV1,↓FVC

↓TLC

Muscular dystrophy[22][23] +/- + +/- - +/- +/- - +/- +/- ↓O2, ↑CO2 ↓FVC, ↓PEF
Pneumonia[24][25][26] + + +/- + +/- +/- - - - Normal Lobar consolidation Normal Normal Productive cough
Aspiration[27][28][29] +/- + +/- + +/- +/- + - - Normal ↓Vt, ↑RV Bronchoscopy
Obstructive sleep apnea[30] + + +/- - +/- + +/- +/- +/- ↓O2, ↑CO2 ↑FRC Polysomnography
Pulmonary hypoplasia[31][32][33] - + +/- - +/- +/- + - - ↓O2, ↑CO2 ↑RV _
Metabolic alkalosis[34][35][36][37] - + +/- - +/- +/- - +/- +/- _ ↓O2, ↑CO2 _ _ _
Sepsis[38][39][40] - + - + +/- +/- - - - Normal ↓O2, ↑CO2 Normal Normal SIRS criteria
ROHHAD[41][42][43] - + +/- - +/- + +/- - - ↓O2, ↑CO2 ↓Vt _
Drugs ( e.g. morphine and barbiturates)
Encephalitis[44][45][46][47] - + - + + - + - - ↓O2, ↑CO2
    • CSF PCR:
      • May reveal HSV-1, HSV-2, VZV, Enterovirus, parechovirus
    • Viruses: IgM and IgG in CSF and serum (acute and convalescent), for antibodies against HSV 1 & 2, VZV, CMV, HHV6, HHV7, enteroviruses, RSV, parvovirus B19, adenovirus, influenza A & B
    • If associated with atypical pneumonia, test serum for:
      • Mycoplasma serology and cold agglutinins
      • Chlamydia serology
  • Brain CT scan may show:
    • In case of HSV, subtle swelling of the frontotemporal region with loss of the normal gyral pattern
  • Brain MRI may show:
    • In case of autoimmune encephalitis, unilateral or bilateral medial temporal T2 high signal
    • In case of encephalitis associated with HSV, frontotemporal atrophy may be observed
 Normal
  • Diagnostic criteria:
    • Major criteria (must be present):
      • Altered mental status (decreased level of consciousness, lethargy) present for greater than equal to 24 hours
    • Minor criteria ( 2 required for possible encephalitis, greater than equal to 3 required for probable or confirmed diagnosis):
      • Fever greater than equal to 24 hours without any other identified cause
      • Seizures without any history of seizure disorders
      • New onset focal neurological deficits
      • EEG changes typical of encephalitis without presence of other causes
      • CSF leukocyte count greater than equal to 5 cells/mm cube
      • Acute brain parenchymal changes of neuroimaging
  • PCR of CSF for viral encephalitis
  • Anti-NMDA-R antibody in the blood or CSF
High cervical dislocation[48][49][50] - + - - - + + - -
  • Normal breath sounds
 ↓O2, ↑CO2 -
  • X-ray:
    • Lateral shows subluxation of vertebral bodies
  • CT scan:
    • Demonstrates bony anatomy of the injury
    • Malalignment or subtle subluxation of facet 
    • Facet fracture associated fractures of the pedicle or lamina
 Normal -
  • Traumatic injuries

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications, and Prognosis

Treatment

Pharmacotherapy

  • Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but were of only limited effectiveness.
  • A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects.
  • If the respiratory depression is from opioid overdose, then the overdose itself is usually treated with an inverse agonist, most likely naloxone, which will itself almost instantaneously stop the respiratory depression if caused by an opioid (and also, depending on the dose, plunge the patient into precipitated withdrawal).

References

  1. ↑ Amiel J, Laudier B, Attié-Bitach T, Trang H, de Pontual L, Gener B; et al. (2003). "Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome". Nat Genet. 33 (4): 459–61. doi:10.1038/ng1130. PMID 12640453.
  2. ↑ Weese-Mayer DE, Berry-Kravis EM, Zhou L, Maher BS, Silvestri JM, Curran ME; et al. (2003). "Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b". Am J Med Genet A. 123A (3): 267–78. doi:10.1002/ajmg.a.20527. PMID 14608649.
  3. ↑ Shannon DC, Marsland DW, Gould JB, Callahan B, Todres ID, Dennis J (1976). "Central hypoventilation during quiet sleep in two infants". Pediatrics. 57 (3): 342–6. PMID 1256944.
  4. ↑ Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM; et al. (2005). "Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial". Lancet. 365 (9460): 663–70. doi:10.1016/S0140-6736(05)17946-X. PMID 15721471.
  5. ↑ Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF; et al. (2005). "Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy". N Engl J Med. 353 (15): 1574–84. doi:10.1056/NEJMcps050929. PMID 16221780.
  6. ↑ Kluckow M (2011). "Functional echocardiography in assessment of the cardiovascular system in asphyxiated neonates". J Pediatr. 158 (2 Suppl): e13–8. doi:10.1016/j.jpeds.2010.11.007. PMID 21238700.
  7. ↑ Sarnat HB (2008). "Disorders of segmentation of the neural tube: Chiari malformations". Handb Clin Neurol. 87: 89–103. doi:10.1016/S0072-9752(07)87006-0. PMID 18809020.
  8. ↑ Marin-Padilla M, Marin-Padilla TM (1981). "Morphogenesis of experimentally induced Arnold--Chiari malformation". J Neurol Sci. 50 (1): 29–55. PMID 7229658.
  9. ↑ Gilbert JN, Jones KL, Rorke LB, Chernoff GF, James HE (1986). "Central nervous system anomalies associated with meningomyelocele, hydrocephalus, and the Arnold-Chiari malformation: reappraisal of theories regarding the pathogenesis of posterior neural tube closure defects". Neurosurgery. 18 (5): 559–64. PMID 3714003.
  10. ↑ Kolb SJ, Kissel JT (2015). "Spinal Muscular Atrophy". Neurol Clin. 33 (4): 831–46. doi:10.1016/j.ncl.2015.07.004. PMC 4628728. PMID 26515624.
  11. ↑ Darras BT (2015). "Spinal muscular atrophies". Pediatr Clin North Am. 62 (3): 743–66. doi:10.1016/j.pcl.2015.03.010. PMID 26022173.
  12. ↑ Mercuri E, Bertini E, Iannaccone ST (2012). "Childhood spinal muscular atrophy: controversies and challenges". Lancet Neurol. 11 (5): 443–52. doi:10.1016/S1474-4422(12)70061-3. PMID 22516079.
  13. ↑ Anandan C, Khuder SA, Koffman BM (2017). "Prevalence of autonomic dysfunction in hospitalized patients with Guillain-Barré syndrome". Muscle Nerve. 56 (2): 331–333. doi:10.1002/mus.25551. PMID 28039863.
  14. ↑ Fokke C, van den Berg B, Drenthen J, Walgaard C, van Doorn PA, Jacobs BC (2014). "Diagnosis of Guillain-Barré syndrome and validation of Brighton criteria". Brain. 137 (Pt 1): 33–43. doi:10.1093/brain/awt285. PMID 24163275.
  15. ↑ Flachenecker P (2007). "Autonomic dysfunction in Guillain-Barré syndrome and multiple sclerosis". J Neurol. 254 Suppl 2: II96–101. doi:10.1007/s00415-007-2024-3. PMID 17503142.
  16. ↑ Laroche CM, Carroll N, Moxham J, Green M (1988). "Clinical significance of severe isolated diaphragm weakness". Am Rev Respir Dis. 138 (4): 862–6. doi:10.1164/ajrccm/138.4.862. PMID 3202460.
  17. ↑ Gierada DS, Slone RM, Fleishman MJ (1998). "Imaging evaluation of the diaphragm". Chest Surg Clin N Am. 8 (2): 237–80. PMID 9619304.
  18. ↑ Sandham JD, Shaw DT, Guenter CA (1977). "Acute supine respiratory failure due to bilateral diaphragmatic paralysis". Chest. 72 (1): 96–8. PMID 872664.
  19. ↑ Benatar M (2006). "A systematic review of diagnostic studies in myasthenia gravis". Neuromuscul Disord. 16 (7): 459–67. doi:10.1016/j.nmd.2006.05.006. PMID 16793269.
  20. ↑ Grob D, Brunner N, Namba T, Pagala M (2008). "Lifetime course of myasthenia gravis". Muscle Nerve. 37 (2): 141–9. doi:10.1002/mus.20950. PMID 18059039.
  21. ↑ Mantegazza R, Beghi E, Pareyson D, Antozzi C, Peluchetti D, Sghirlanzoni A; et al. (1990). "A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy". J Neurol. 237 (6): 339–44. PMID 2277266.
  22. ↑ Takasugi T, Ishihara T, Kawamura J, Sasaki K, Toyoda T, Oosumi M; et al. (1995). "[Blood gas changes in Duchenne type muscular dystrophy]". Nihon Kyobu Shikkan Gakkai Zasshi. 33 (1): 17–22. PMID 7699962.
  23. ↑ Mayer OH, Finkel RS, Rummey C, Benton MJ, Glanzman AM, Flickinger J; et al. (2015). "Characterization of pulmonary function in Duchenne Muscular Dystrophy". Pediatr Pulmonol. 50 (5): 487–94. doi:10.1002/ppul.23172. PMC 4402127. PMID 25755201.
  24. ↑ Almirall J, Bolíbar I, Balanzó X, González CA (1999). "Risk factors for community-acquired pneumonia in adults: a population-based case-control study". Eur Respir J. 13 (2): 349–55. PMID 10065680.
  25. ↑ Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF; et al. (2016). "Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia". Clin Infect Dis. 62 (7): 817–823. doi:10.1093/cid/civ1214. PMC 4787606. PMID 26747825.
  26. ↑ Musher DM, Thorner AR (2014). "Community-acquired pneumonia". N Engl J Med. 371 (17): 1619–28. doi:10.1056/NEJMra1312885. PMID 25337751.
  27. ↑ Wu YC, Hsu PK, Su KC, Liu LY, Tsai CC, Tsai SH; et al. (2009). "Bile acid aspiration in suspected ventilator-associated pneumonia". Chest. 136 (1): 118–124. doi:10.1378/chest.08-2668. PMID 19318678.
  28. ↑ Bynum LJ, Pierce AK (1976). "Pulmonary aspiration of gastric contents". Am Rev Respir Dis. 114 (6): 1129–36. doi:10.1164/arrd.1976.114.6.1129. PMID 1008348.
  29. ↑ DePaso WJ (1991). "Aspiration pneumonia". Clin Chest Med. 12 (2): 269–84. PMID 1855371.
  30. ↑ Abdeyrim A, Zhang Y, Li N, Zhao M, Wang Y, Yao X; et al. (2015). "Impact of obstructive sleep apnea on lung volumes and mechanical properties of the respiratory system in overweight and obese individuals". BMC Pulm Med. 15: 76. doi:10.1186/s12890-015-0063-6. PMC 4513967. PMID 26209328.
  31. ↑ Vergani P (2012). "Prenatal diagnosis of pulmonary hypoplasia". Curr Opin Obstet Gynecol. 24 (2): 89–94. doi:10.1097/GCO.0b013e3283505a86. PMID 22249145.
  32. ↑ Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC; et al. (2012). "Clinical features of paediatric pulmonary hypertension: a registry study". Lancet. 379 (9815): 537–46. doi:10.1016/S0140-6736(11)61621-8. PMC 3426911. PMID 22240409.
  33. ↑ Tsukimori K, Masumoto K, Morokuma S, Yoshimura T, Taguchi T, Hara T; et al. (2008). "The lung-to-thorax transverse area ratio at term and near term correlates with survival in isolated congenital diaphragmatic hernia". J Ultrasound Med. 27 (5): 707–13. PMID 18424645.
  34. ↑ Mennen M, Slovis CM (1988). "Severe metabolic alkalosis in the emergency department". Ann Emerg Med. 17 (4): 354–7. PMID 2833137.
  35. ↑ Fitzgibbons LJ, Snoey ER (1999). "Severe metabolic alkalosis due to baking soda ingestion: case reports of two patients with unsuspected antacid overdose". J Emerg Med. 17 (1): 57–61. PMID 9950389.
  36. ↑ Gawarammana IB, Coburn J, Greene S, Dargan PI, Jones AL (2007). "Severe hypokalaemic metabolic alkalosis following ingestion of gaviscon". Clin Toxicol (Phila). 45 (2): 176–8. doi:10.1080/15563650600981160. PMID 17364637.
  37. ↑ Oster JR, Materson BJ, Rogers AI (1980). "Laxative abuse syndrome". Am J Gastroenterol. 74 (5): 451–8. PMID 7234824.
  38. ↑ Graciano AL, Balko JA, Rahn DS, Ahmad N, Giroir BP (2005). "The Pediatric Multiple Organ Dysfunction Score (P-MODS): development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children". Crit Care Med. 33 (7): 1484–91. PMID 16003052.
  39. ↑ Wilkinson JD, Pollack MM, Glass NL, Kanter RK, Katz RW, Steinhart CM (1987). "Mortality associated with multiple organ system failure and sepsis in pediatric intensive care unit". J Pediatr. 111 (3): 324–8. PMID 3625400.
  40. ↑ Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis (2005). "International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics". Pediatr Crit Care Med. 6 (1): 2–8. doi:10.1097/01.PCC.0000149131.72248.E6. PMID 15636651.
  41. ↑ duRivage SK, Winter RJ, Brouillette RT, Hunt CE, Noah Z (1985). "Idiopathic hypothalamic dysfunction and impaired control of breathing". Pediatrics. 75 (5): 896–8. PMID 3991276.
  42. ↑ FISHMAN LS, SAMSON JH, SPERLING DR (1965). "PRIMARY ALVEOLAR HYPOVENTILATION SYNDROME (ONDINE'S CURSE)". Am J Dis Child. 110: 155–61. PMID 14320765.
  43. ↑ Paz-Priel I, Cooke DW, Chen AR (2011). "Cyclophosphamide for rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome". J Pediatr. 158 (2): 337–9. doi:10.1016/j.jpeds.2010.07.006. PMC 3976575. PMID 20727534.
  44. ↑ Liu XJ, Li W, Zhang YQ, Liu YM, Liu LZ (December 2009). "[Clinical features and treatment of serious brainstem encephalitis caused by enterovirus 71 infection]". Zhongguo Dang Dai Er Ke Za Zhi (in Chinese). 11 (12): 967–9. PMID 20113599.
  45. ↑ Zhang YC, Li XW, Zhu XD, Qian SY, Shang YX, Li BR, Liu XL (2010). "Clinical characteristics and treatment of severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71 in China". World J Emerg Med. 1 (2): 108–13. PMC 4129752. PMID 25214951.
  46. ↑ "Aseptic meningitis and encephalitis: the role of PCR in the diagnostic laboratory".
  47. ↑ Mann AP, Grebenciucova E, Lukas RV (2014). "Anti-N-methyl-D-aspartate-receptor encephalitis: diagnosis, optimal management, and challenges". Ther Clin Risk Manag. 10: 517–25. doi:10.2147/TCRM.S61967. PMC 4085332. PMID 25061311.
  48. ↑ "Critical Care Medicine: Principles of Diagnosis and Management in the Adult ... - Joseph E. Parrillo, R. Phillip Dellinger - Google Books".
  49. ↑ Yu E, Romero N, Miles T, Hsu SL, Kondrashov D (October 2016). "Dyspnea as the Presenting Symptom of Cervical Spondylotic Myelopathy". Surg J (N Y). 2 (4): e147–e150. doi:10.1055/s-0036-1597664. PMC 5553503. PMID 28825009.
  50. ↑ "Dyspnea Caused by Atlantoaxial Subluxation in a Patient with Rheumatoid Arthritis".


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