Tag Archives: pulmonary

Approach to Tachypnea in the ED Setting

Author: Dorian Alexander, MD (Associate Program Director, Director of Critical Care in Emergency Medicine, Brookdale University Hospital, Brooklyn, NY) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit)

Case 1:

A 19 year old female with a past medical history of asthma controlled with an albuterol inhaler presents to the ED with a chief complaint of shortness of breath. Her vital signs at triage include T 98.7F, BP 135/78, HR 108, RR 36, SpO2 100% RA.

She reports visiting a friend’s house with multiple cats and has not used her inhaler for the past two days. Today, she notes that she’s wheezing significantly, and it’s hard to breathe. Her initial peak flow is 150 with a known baseline of 350.

On exam, she’s well-appearing but tachypneic with diffuse wheezing on auscultation bilaterally without rales or rhonchi, 5 -7 word dyspnea, (+)s1s2  tachycardic without JVD, no LE edema, and an abdomen that’s soft and NT/ND.

The patient is placed on a series of nebulization treatments with albuterol and ipratropium, with improvement in her symptoms. Prednisone 60mg orally is administered, and the patient is observed for a period of time. After 3 rounds of nebulization, the peak flow has improved to 350, and she’s able to ambulate without distress in the ED. Repeat exam shows resolution of wheezing with clear lung fields bilaterally.  She’s able to be discharged from the ED with a prescription for steroids and an inhaler.


The presentation of shortness of breath is one of the most common chief complaints in the Emergency Department and primary care settings.1 Tachypnea is a symptom of an underlying process and is not a disease itself. Tachypnea in the ED is different from the subjective sensation of “shortness of breath.” Patients can be short of breath but not tachypneic.

It can be helpful to define a few terms to better understand tachypnea. Abnormally fast breathing can present as rapid shallow breathing (tachypnea) or rapid deep breathing (hyperpnea), while dyspnea refers to the sensation of shortness of breath.

A consensus statement from the American Thoracic Society defines dyspnea in the following way: “Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity.”1

For the purpose of this discussion we will evaluate tachypnea as both rapid and deep breathing abnormalities noted on clinical presentation as a subset of a patient’s presenting symptoms inclusive of dyspnea.

The definition and clinical presentation of abnormally fast breathing should generate the following question in every clinician’s mind – why is the breathing abnormal? The answer lies in the pathophysiology of dyspnea.

Pathophysiology of Dyspnea


Fig 12

The pathophysiology of dyspnea is related to multiple complex interactions between organ systems – the respiratory, cardiovascular, neurological systems, and oxygen carriers all play a role in the development of tachypnea and dyspnea.3 Stimulation of such receptors can be achieved by direct and indirect methods leading to multiple factors simultaneously playing a role in a patient’s clinical pathology.4

Physiologic receptors of tachypnea


Fig 25

The end point of receptor stimulation is dyspnea and tachypnea.6 Primary pulmonary receptors such as wall stretch and lower airway receptors are commonly stimulated by intra-pulmonary pathologies such as COPD/Asthma/CHF; however, chemoreceptors such as medullary and carotid body receptors are often affected by extra-pulmonary factors.3,6 The identification of extra-pulmonary factors as etiologies of dyspnea is a vital aspect of the Emergency Physician’s evaluation of acute dyspnea.

Given such complex etiologies of dyspnea and tachypnea, a systematic approach to the diagnosis and management of tachypnea will more often yield an accurate diagnosis with appropriate bedside interventions.

Pulmonary Etiologies of Tachypnea

The pulmonary system is the first organ system that is evaluated at the bedside in patients with acute dyspnea and tachypnea. Primary pulmonary pathologies can be readily identified through the use of appropriate lung physical exam techniques and radiologic imaging. History, physical exam, EKG, chest x-ray, and labs as necessary can usually yield the diagnosis in the majority of cases.

The use of point of care ultrasound (POCUS) as an adjunct to bedside evaluation of pulmonary pathology in patients with dyspnea and tachypnea should be incorporated into daily practice.



Fig 3: Asthma on chest x-ray with A-Lines on lung ultrasound 7,8


Fig 4: Pneumonia on chest x-ray with lung ultrasound findings 9,10


Fig 5: Pulmonary edema on chest x-ray with diffuse B-lines on lung ultrasound 8,11


Fig 6: Pneumothorax on chest x-ray with stratosphere sign on lung ultrasound 8,12

Case 2:

A 68 year old male with a past medical history of ESRD on hemodialysis presents to the ED with acute tachypnea. His last hemodialysis session was two days ago, and the patient completed 4 hours. Vital signs at triage include T 97.6F, BP 95/55, HR 104, RR 34, SpO2 92% RA, 98% 5L NC.

On exam, the patient appears uncomfortable with mild bibasilar crackles and is tachypneic, only able to speak in intermittent sentences, (+) s1s2 muffled, (+) JVD, (+) 1 b/l LE edema. His abdomen is soft and nontender.

Bedside lung ultrasound reveals minimal B-lines with scattered A-lines and no ultrasonographic evidence of pneumothorax. Cardiac echo reveals a pericardial effusion with bowing of the right ventricle.

The patient is placed on a cardiac monitor with 5L of supplemental oxygen via nasal cannula, and his oxygen saturation increases to 98%. Intravenous fluid with normal saline is started at 100ml/hr after an initial bolus of 500ml, and his repeat BP is 128/68. Bedside EKG shows sinus tachycardia with electrical alternans. Follow up chest x-ray shows an enlarged cardiac silhouette that is increased compared to an x-ray from one month prior.

A diagnosis of pericardial tamponade is made at the bedside, and with Cardiothoracic Surgery consultation, the patient is taken to the OR for a pericardial window.

Cardiovascular Etiologies of Tachypnea

Extra-pulmonary causes of tachypnea usually pose the biggest challenge to clinicians at the bedside. The cardiovascular system should always be considered as a potential etiology of undifferentiated tachypnea. Evaluation of heart sounds with murmurs on physical exam, presence or absence of JVD, pitting edema, and hepatomegaly can all indicate a cardiac etiology of symptoms.

Screening tools such as EKG and chest x-ray may reveal findings that lead to increased suspicion for primary cardiovascular origins of a patient’s dyspnea; however, they more often yield nonspecific information.  POCUS showing pericardial effusion, tamponade physiology, diffuse B-lines, or RV > LV size may provide a higher diagnostic yield when combined with history, physical exam, EKG, and chest x-ray.13–16



Fig 7 Pericardial effusion with tamponade physiology  and electrical alternans on EKG17,18


Fig 8    RV dilation and dysfunction in acute pulmonary embolus19

Hematologic Etiologies of Tachypnea

Case 3:

A 93 year old female with a past medical history of dementia is sent to the ED for increased SOB over the past two days. At baseline, the patient is non-ambulatory, non-verbal, fed via a PEG tube, and she is a full code as per her MOLST form. Her vital signs at triage are T 96.3F, BP 90/58, HR 110, RR 32, SpO2 98% RA.

On exam, the patient is a pale-appearing elderly female with notable tachypnea, clear lungs, mildly decreased breath sounds at the bases, (+) s1s2 tachycardic with a systolic ejection murmur, a soft abdomen that’s NT/ND, normal bowel sounds, a c/d/I PEG site, rectal exam (+) melena, (+) conjunctival pallor, and loss of visualization of her palmar crease.

The patient is placed on cardiac monitoring with large bore IVs and given an initial bolus of normal saline. Her repeat BP increases to 110/68, with a reduction in her HR to 84. Her EKG and CXR show NSR and bibasilar atelectasis, respectively. Her lab work is notable for a Hgb of 4 (baseline of 8 from 1 month prior) and an INR of 2.8 (the patient is on anticoagulation for DVT). The patient is transfused two units of PRBCs in the ED, started on a PPI drip, and her coagulopathy is reversed with FFP and vitamin K. The patient is adequately resuscitated with appropriate response to transfusion and admitted to the medical intensive care unit.

Hemoglobin (Hgb) acts as the major transporter of oxygen in the blood, and an acute or chronic drop in blood Hgb concentration can reduce its oxygen carrying capacity.20 In a compensatory mechanism to maintain oxygenation, neurological and carotid chemoreceptors are stimulated to maintain oxygenation by increasing minute ventilation.20 This increase in minute ventilation appears as an acute change in a patient’s baseline respiratory effort. Anemia is an often unrecognized etiology of dyspnea and tachypnea, as pending labs can delay diagnosis. However, appropriate physical exam findings can lead to earlier recognition and intervention.21

Metabolic Etiologies of Tachypnea

Case 4:

A 9 year old male with no prior medical history presents to the ED with his mother complaining of abdominal pain.  As per his mother, he has been asking for a lot of water lately and going to the bathroom very often over the past 3 days. He developed one episode of vomiting today which progressed to abdominal pain. His vital signs at triage in include T 99F, BP 98/57, HR 120, RR 34, SpO2 100% RA, BGM – HIGH.

On exam, the patient is noted to be dehydrated and tired-appearing with deep, fast respirations and a questionable fruity odor on his breath, lungs clear bilaterally, (+) s1s2 tachycardic with no murmurs noted, a soft abdomen that is NT/ND, dry MM, and poor skin turgor.

The patient is immediately placed on a cardiac monitor with bilateral large bore IVs. A 20mg/kg fluid bolus is administered twice with labs drawn to evaluate for DKA including serum ketones and a venous blood gas. Initial results show a pH of 7.2, with a pCO2 of 16, and an anion gap of 22. The patient is immediately started on an insulin drip and admitted to the pediatric ICU for new onset diabetes and DKA.

Metabolic acidosis from a range of causes can lead to tachypnea. As the body attempts to compensate for worsening acidosis, the respiratory rate increases to reduce the pCO2 and maintain a compensated physiological pH.22 In many patients, this compensatory respiratory drive can be both visually impressive, as  patients are generating large tidal volumes and may tire due to increased work of the respiratory muscles. The compensatory respiratory rate in metabolic acidosis is the driving force behind the tachypnea and dyspnea experienced by this subset of patients. The important clinical point to always consider is correction of the underlying etiology and not the tachypnea itself. Physiologic respiratory compensation mechanisms are very efficient in maintaining a respiratory alkalosis to compensate for a metabolic acidosis; however, a patient can tire out if the underlying cause is not treated and thus rapidly decompensate with hypercarbic respiratory failure and worsening metabolic acidosis leading to life-threatening acidemia, cardiac arrest, and death. Although the causes of metabolic acidosis are multifactorial, new onset DKA is a common ED presentation that every clinician should immediately identify based on available history, physical exam, and an easily obtainable POC blood glucose.

Management & Treatment

The multifactorial nature of tachypnea and dyspnea leads to complex management and treatment options depending on the underlying process involved. The primary goal is to always treat the primary etiology and support the respiratory system via adjunctive therapies as necessary. The detailed management of all causes of tachypnea is beyond the scope of this discussion; however, we can make some broad generalizations by organ system.

Pulmonary: Adjunctive respiratory support in the form of inhaled beta agonists and anticholinergics for bronchospasm induced disease states with additional steroids to reduce inflammation over time are the mainstay in asthma and COPD exacerbations. Diuretics work to reduce extravascular fluid in CHF states, and nitrates can assist in fluid redistribution for CHF. It’s important to note that these medications often do not provide instant relief, and patients in acute distress from bronchospastic disease or acute pulmonary edema might benefit from the initiation of non-invasive ventilation in the form of BIPAP or CPAP. Laboratory studies, although not always necessary in reversible exacerbations of asthma, might include CBC, BMP, a blood gas, troponin, and BNP. Radiologic studies in the form of chest x-ray combined with bedside lung ultrasound often confirm the diagnosis.

Cardiovascular: Cardiac causes may overlap with pulmonary etiologies: for example, an NSTEMI leading to decompensated CHF. Although workup strategies may be similar, the addition of bedside cardiac ECHO can reveal important diagnostic information. The presence of a pericardial effusion and tamponade physiology will lead to emergent changes in bedside management. RV: LV > 0.9 raises clinical suspicion for PE, and thus additional diagnostic testing such as a bilateral LE duplex and a CTA of the chest could be performed leading to earlier diagnosis and treatment.

Hematologic: Hematologic emergencies can have a broad range of management options and treatment modalities, not all of which are available in the ED. Symptomatic anemia however, is one medical emergency that should be recognized by the Emergency Physician and treated with appropriate blood product transfusion in the form of PRBCs, FFPs, and platelets as necessary.

Metabolic: Tachypnea and dyspnea from metabolic causes are a direct compensatory mechanism due to the underlying acidosis. A comprehensive differential for the evaluation of metabolic acidosis is beyond the scope of this discussion, but common etiologies such as DKA, which is managed with IVF resuscitation and initiation of insulin therapy to correct the anion gap acidosis must be recognized at the bedside for early initiation of therapy and reversal of acidosis. Other causes of metabolic acidosis, especially those related to renal failure or potentially lethal toxic overdoses, may require hemodialysis for correction.

Summary & Take Home Points

Tachypnea can be the presentation of multiple different pathologies. A focused history and physical exam, along with an understanding of the pathophysiology of appropriate disease states, can lead to thorough evaluation and management at the bedside. A systematic organ system approach to the patient can quickly lead to bedside diagnosis and initiation of treatment in patients with undifferentiated tachypnea.

As Emergency Physicians we should:

  • Avoid anchoring on the pulmonary system as the only cause of tachypnea
  • Maintain a broad differential for extra-pulmonary causes of tachypnea
  • Use bedside ultrasound in the setting of undifferentiated tachypnea; lung US can reveal pathology of PTX, Asthma, CHF, and PNA effectively and accurately
  • Utilize follow up chest x-ray to improve diagnostic ability
  • Combine EKG findings with bedside ECHO to quickly identify life threatening conditions
  • Remember that metabolic acidosis can present as tachypnea & point of care testing can give clues to an early diagnosis of DKA


References/Further Reading:

  1. Parshall MB, Schwartzstein RM, Adams L, et al. An official American thoracic society statement: Update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med. 2012;185(4):435-452. doi:10.1164/rccm.201111-2042ST.
  2. Laviolette L, Laveneziana P. Dyspnoea: A multidimensional and multidisciplinary approach. Eur Respir J. 2014;43(6):1750-1762. doi:10.1183/09031936.00092613.
  3. Ashton MD R, Raman MD D. Dyspnea. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/dyspnea/. Published 2015. Accessed June 11, 2016.
  4. Sharma V, Fletcher SN. Review Article. N Engl J Med. 2014;333(23):1-9. doi:10.1111/anae.12709.
  5. Kabrhel C. Approach to the Patient with Undiffrentiated Dyspnea.; 2012.
  6. Burki NK, Lee LY. Mechanisms of Dyspnea. Chest. 2010;138(5):1196-1201. doi:10.1378/chest.10-0534.
  7. Bickle I. Hyperinflated lungs in Asthma. https://radiopaedia.org/cases/hyperinflated-lungs.
  8. Touw HRW, Tuinman PR, Gelissen HPMM, Lust E, Elbers PWG. Lung ultrasound: Routine practice for the next generation of internists. Neth J Med. 2015;73(3):100-107.
  9. Kwong Y. Pneumonia. https://radiopaedia.org/cases/klebsiella-pneumonia-1.
  10. Zhan C, Grundtvig N, Klug BH. Performance of Bedside Lung Ultrasound by a Pediatric Resident A Useful Diagnostic Tool in Children With Suspected Pneumonia. Pediatr Emerg Care. 2016;0(0):1-5.
  11. Dixon A. CHF. https://radiopaedia.org/cases/pulmonary-oedema-5.
  12. Jaff M. Pneumothorax. https://radiopaedia.org/cases/pneumothorax-14.
  13. Lichtenstein DA. BLUE-Protocol and FALLS-Protocol. Chest. 2015;147(6):1659-1670. doi:10.1378/chest.14-1313.
  14. Ultrasonography P, Moore CL, Copel JA. Point-of-Care Ultrasonography. N Engl J Med. 2011;364(8):749-757. doi:10.1056/NEJMra0909487.
  15. Koenig S, Chandra S, Alaverdian A, Dibello C, Mayo PH, Narasimhan M. Ultrasound assessment of pulmonary embolism in patients receiving CT pulmonary angiography. Chest. 2014;145(4):818-823. doi:10.1378/chest.13-0797.
  16. Bataille B, Riu B, Ferre F, et al. Integrated use of bedside lung ultrasound and echocardiography in acute respiratory failure: a prospective observational study in ICU. Chest. 2014;146(6):1586-1593. doi:10.1378/chest.14-0681.
  17. Maung M. Khin Hou R, I. Martin A, A. Bassily E, Coffman GJ, A. Siddique M, M. Whitaker D. Redistribution of pericardial effusion during respiration simulating the echocardiographic features of cardiac tamponade. Int J Case Reports Images. 2016;7(4):261. doi:10.5348/ijcri-201645-CR-10633.
  18. Roediger J. Electrical Alternans. http://ecgguru.com/ecg/electrical-alternans. Published 2012.
  19. Presently E, Tte E, States U. Role of Echocardiography in Patients with Acute Pulmonary Thromboembolism. Journal of Cardiovascular Ultrasound. 2008;16(1):9-16.
  20. Ferrari M, Manea L, Anton K, et al. Anemia and hemoglobin serum levels are associated with exercise capacity and quality of life in chronic obstructive pulmonary disease. BMC Pulm Med. 2015;15:58. doi:10.1186/s12890-015-0050-y.
  21. Santra G. Usefulness of examination of palmar creases for assessing severity of anemia in Indian perspective: A study from a tertiary care center. Int J Med Public Heal. 2015;5(2):169. doi:10.4103/2230-8598.153830.
  22. Ingelfinger JR, Seifter JL. Disorders of Fluids and Electrolytes Integration of Acid–Base and Electrolyte Disorders. N Engl J Med. 2014;19371(6):1821-1831. doi:10.1056/NEJMra1215672.


Hemoptysis: Key principles and management

Authors: Patrick C Ng, MD (EM Chief Resident, SAUSHEC Emergency Medicine Department) and Brit Long, MD (@long_brit, EM Attending Physician, SAUSHEC Emergency Medicine Department) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)

Case 1

After being discharged from your hospital after a three-day stay for a bowel obstruction, a 76- year old male presents with two days of cough productive of green sputum with red streaks. He reports no relief with the use of his inhalers that he normally uses for his chronic obstructive pulmonary disease (COPD). Upon reviewing his chart, you notice that he had no cough during his hospital stay. His review of systems is positive for chills, intermittent nausea, and chest discomfort when actively coughing.

On examination, his vital signs are blood pressure (BP) 170/90, heart rate (HR) 110 beats per minute (bpm), respiratory rate (RR) 30 per minute, oxygen saturation (Sat) of 92% on room air (RA), and temperature (temp) of 101.6°Farenheit (F). He is actively coughing and is in mild distress. He coughs up about 1 cc of purulent material with red streaks in it. His right lower lung fields have significant crackles. Cardiac examination reveals tachycardia. Laboratory tests are significant for a white blood cell count of 16 x 109/L, a creatinine of 1.5mg/dL, and lactate of 2.5. Chest x-ray reveals a right lower lobe (RLL) infiltrate.

You make the diagnosis of hospital acquired pneumonia, start antibiotics and intravenous (IV) fluids and admit the patient for further management.

Case 2

An 80-year-old female presents to your emergency department (ED) with a sudden onset of shortness of breath. She recently completed a trans-Atlantic flight from London. Upon arrival to her room, you notice that she is in respiratory distress. She has never had anything like this before, and has no relief with oxygen supplementation. Her review of systems is positive for cough productive of reddish sputum.

Physical examination is significant for a swollen right calf. Her vital signs are: BP 80/60, HR 140, RR 46, Sat 88% on room air, and a Temp 100.3°F. Her EKG shows sinus tachycardia, and a bedside echocardiogram shows a dilated right ventricle (RV).

Suddenly, the patient goes into cardiac arrest. You start standard advanced cardiac life support (ACLS) protocol, intubate the patient, and call for tissue plasminogen activator (tPA) because you suspect a massive pulmonary embolism (PE) as the diagnosis. After rounds of chest compressions and a dose of tPA, you achieve return of spontaneous circulation (ROSC). You start post arrest hypothermia protocol and admit the patient to the medical intensive care unit (MICU).


Hemoptysis is defined as the expectoration of blood originating from the tracheobronchial tree or lung parenchyma1. A common source of the bleeding is the bronchial artery1,2. Blood coming from other sources, including but not limited to the oral cavity, upper gastrointestinal (GI) tract, or esophagus can sometimes be mistaken for hemoptysis and is categorized as pseudohemoptysis. There are numerous causes of hemoptysis. Ong et al divides such etiologies into 5 main categories: infective, neoplastic, vascular, autoimmune, and drug/other related.

Examples of infectious causes include tuberculosis, lung abscesses, and pneumonia. Primary and metastatic cancer are examples of neoplastic causes. Pulmonary embolism is a vascular cause of hemoptysis. Lupus and various vasculitic diseases are examples of autoimmune causes of hemoptysis. Anticoagulants and trauma can cause hemoptysis as well1. According to a retrospective population based study conducted by Abdulmalak et al from 2008-2012, 15,000 adults were admitted for hemoptysis each year. The investigators found hemoptysis is associated with a 27% mortality at three years2.

There are two main categories of hemoptysis: massive and non-massive. The initial evaluation should try to focus on this differentiation. Most cases of hemoptysis are non-massive (95%) and self-limited3. Massive hemoptysis is described as a large enough volume of blood expectorated to cause hemodynamic instability, abnormal gas exchange, or a significant threat to life. According to Yoon et al, most deaths that occur secondary to massive hemoptysis are due to asphyxiation, rather than exanguination4. There is no consensus on the volume of blood that needs to be expectorated to be categorized as massive hemoptysis. Some reports define massive hemoptysis as expectorating >300 cc of blood in 24 hours5. Other sources have described massive hemoptysis as expectorating >100 to >1000 cc of blood in 24 hours4-6. With no clear definition on what volume of blood must be lost to meet the diagnosis of massive hemoptysis, the emergency physician must target his/her evaluation to determine the risk of death with the patient’s clinical presentation, regardless of how much blood is expectorated.

Key ED Work Up

For patients presenting with hemoptysis, the emergency medicine (EM) provider must determine whether it is massive or not and what etiology (infectious, vascular, etc) to suspect by history and physical examination. Laboratory work including a complete blood count, a basic metabolic panel, a type and screen (with cross if massive hemoptysis suspected), coagulation studies (particularly important in patients on anticoagulation) and a lactate level should be considered. Since patients with massive hemoptysis can decompensate quickly, the EM provider should not fall into a false sense of assurance if initial laboratory work and evaluation are normal. These patients should be monitored closely and labs repeated if there are signs of clinical deterioration.

Important imaging to consider includes chest radiograph and computed tomography (CT)7. Chest CT is needed in patients with history of tobacco use, age greater than 40 years, massive hemoptysis, and mass or infiltrate on radiograph. Bronchoscopy should be considered, as it can help to localize and control the source of bleeding by infusion of vasoactive drugs at the site of the bleeding. However, the performance of this procedure can be challenging secondary to a blood filled airway6-8.

Radiographs and CT can help locate the bleeding and possibly characterize an infectious, neoplastic, or other cause of the bleeding8-11. Table 1 summarizes a set of guidelines for imaging patients that present with hemoptysis.


Table 1: Imaging recommendations (Reproduced from Earwood et al. Am Fam Physician 2015)

Key ED Work Up: Non-Massive Hemoptysis

In patients determined to have pseudohemoptysis and/or non-massive hemoptysis, it may be appropriate to discharge these patients with follow up testing/imaging if indicated according to their history and physical (Figure 1). Patients should be hemodynamically stable with normal vital signs, have normal chest radiographs, possess no comorbidities, and have adequate follow-up. Repeat chest radiograph may be needed. Any concern for massive hemoptysis warrants admission for further evaluation and management.


Figure 1: Evaluation of non-massive hemoptysis (Table reproduced from Ong et al. Singapore Med J 2015)

Key ED Work Up: Massive Hemoptysis

Massive hemoptysis requires immediate resuscitation with blood products, interventional radiology consultation (for bronchial artery embolization), and cardiothoracic surgery consultation. As mentioned in the introduction, asphyxiation is a cause of death in patients with hemoptysis. Early and aggressive airway management should be considered. When intubating, large (8.0) ET tubes are preferred, as smaller tubes, as well as double lumen tubes, can make bronchoscopy difficult. One should also consider the utility of selective mainstem bronchus intubation to isolate the side that is bleeding. One can accomplish this by placing the tube past the cords and then rotating the tube 90 degrees toward the side that one is trying to intubate13.

In patients on anticoagulation, reversal may be needed. Some medications to consider, depending on the specific anticoagulant, include prothrombin complex concentrate (PCC), TXA (tranexamic acid) vitamin K, fresh frozen plasma (FFP), and recombinant Factor VII14. For further information on reversal of anticoagulation please visit: http://www.emdocs.net/reversal-of-anticoagulation/. Blood products may be required.

In patients with massive hemoptysis, hemodynamic instability, or significant comorbidities, the emergency provider should consider admission for further workup. Inpatient workup may involve bronchoscopy, endovascular embolization, and/or surgery (Figure 2).


Figure 2: A management approach to massive hemoptysis (Image reproduced from Larici et al. Diagn Interv Radiol 2014)


-Hemoptysis is defined as expectoration of blood originating from the tracheobronchial tree or lung parenchyma and must be distinguished from pseudohemoptysis

-Hemoptysis is categorized as Massive or Non-massive

-There are many causes of hemoptysis and broad categories of these causes include: Infection, Autoimmune, Trauma, Drugs, and Neoplastic

-There is no consensus on the volume of expectorant that one must have to meet the diagnosis of massive hemoptysis

-Massive hemoptysis is life threatening, and, after securing the airway with intubation and maximizing hemodynamic stability with transfusion and reversal of anticoagulation, the patient should be admitted.

-Depending on the suspected etiology, definitive care may come in the form of bronchoscopy, bronchial artery embolization, and/or surgery

References / Further Reading

  1. Ong Z, Chai H, How C, Koh J, Low TB. A simplified approach to haemoptysis. Singapore Med J 2015; 57(8): 415-418.
  2. Abdulmalak C, Cottenet J, Beltramo G, Georges M, Camus P, Bonniaud P, et al. Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database. Eur Respir J 2015 Aug;46(2):50311.
  3. Larici AR, Franchi P, Occhipinti M, Contegiacomo A, Ciello A, Calandriello L, et al. Diagnosis and management of hemoptysis. Diagn Intervn Radiol 2014 Jul-Aug; 20(4):299-309.
  4. Yoon Woong, Kim JK, Kim YH, Chung TW, Kang HK. Bronchial and Nonbronchial Systemic Artery Embolization for Life-threatening Hemoptysis: A Comprehensive Review. Radiographics 2002 Nov-Dec;22(6):1395-409.
  5. Andersen PE. Imaging and interventional radiological treatment of hemoptysis. Acta Radiol 20016 Oct;47(8):780-92.
  6. Jean-Baptiste E. Clinical assessment and management of massive hemoptysis. Crit Care Med 2000;28:1642-1647.
  7. McGuinness G, Beacher JR, Harkin TJ, Garay SM, Rom WN, Naidich DP. Hemoptysis: 30 prospective high-resolution CT/bronchoscopic correlation. Chest 1994:105:1155-1162.
  8. Cahill BC, Ingabar DH. Massive hemoptysis: assessment and management. Clin Chest Med 1994; 15:147-167.
  9. Nadich DP, Funt S, Ettenger NA, Arranda C. Hemoptysis: CT—bronchoscopic correlations in 58 cases. Radiology 1990:357-362.
  10. Abal AT, Nair PC, Cherian J. Haemoptysis: aetiology, evaluation, and outcome—a prospective study in a third-world county. Respir Med 2001;95:548-552.
  11. Tak S, Ahluwalia G, Sharma SK, Mukhopadhya S, Pande JN. Haemoptysis in patients with a normal chest radiograph: bronchoscopy-CT correlation. Australas Radiol 1999; 43:451-455.
  12. Earwood JS, Thompson TD. Hemoptysis: Evaluation and Management. Am Fam Physician 2015 Feb 15;91(4):243-249.
  13. Bair AE, Doherty MJ, Harper R, Albertoson TE. An evaluation of a blond rotational technique for selective mainstem intubation. Acad Emerg Med 2004;11(10):1105-7.
  14. Sakr L, Dutau H. Massive Hemoptysis: An Update on the Role of Bronchoscopy in Diagnosis and Management. Respiration 2010;80:38-58.

Cystic Fibrosis: ED Management, Pearls and Pitfalls

Authors: Stephanie Tassin, MD (EM Resident at SAUSHEC) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital)


Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that affects multiple organ systems via mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. In short, a defective CFTR channel prevents mucous and exocrine glands from secreting chloride. Without chloride, water cannot follow, and the end result is thick, hyperviscous secretions in the lung, sinuses, pancreas, intestines, and biliary system [1].  In the sweat glands, chloride reabsorption is impaired, leading to excess sodium chloride loss. With excessive sweating, this can lead to hyponatremic hypochloremic dehydration. It also has detrimental effects on the reproductive, musculoskeletal, and urinary systems, but these are rarely relevant in the Emergency Department (ED) [2].

CF affects 1 in 3,200 Caucasian births and is primarily thought of as a Caucasian disease, though it is also seen in other ethnicities at lower frequencies. As of 2014, less than 2/3 of cases are detected by newborn screening, so providers must keep it on their differential, especially in young children with recurrent pulmonary infections, sinus infections, failure to thrive, and constipation or meconium ileus [2].

Case 1

A 22 year old female with cystic fibrosis presents to you complaining of increasing shortness of breath over the last week. Her chronic cough has gotten worse recently and it is productive of occasionally blood-tinged and green sputum. She reports low-grade fevers at home as well as fatigue, headache, and anorexia. She just moved to town and has no medical records in your system. Vital signs include blood pressure (BP) 110/64, heart rate (HR) 110, respiratory rate (RR) 34, oxygen saturation (SpO2) 92% on room air, temperature (T) 100.1°Farenheit (F) orally. Her examination is remarkable for coarse breath sounds with scattered expiratory wheezes, a slightly increased work of breathing, and clubbing of her fingernails. Her chest x-ray is shown below.



You put her on oxygen by nasal cannula and give her a small intravenous (IV) fluid bolus, but you wonder what to do next. You do not see a lot of patients with CF, but you see a lot of chronic obstructive pulmonary disease (COPD), and she looks almost exactly like a patient with a COPD exacerbation. Do you just treat her like COPD with nebulizer treatments, steroids, antibiotics, and bi-level positive pressure ventilation (BiPAP)? What antibiotics do you use? Is there anything else you can offer?

CF Pulmonary Exacerbations

Progressive pulmonary disease accounts for 85% of the mortality in CF[3]. From a young age, the CF patient is colonized with a predictable spectrum of bacteria that persist and cause chronic infection and inflammation [1]. Typically, this causes a persistent, productive cough and an obstructive pattern on pulmonary function tests. This may progress to chronic bronchitis and bronchiectasis with occasional exacerbations. These pulmonary exacerbations are generally characterized by increasing dyspnea, tachypnea, changes in sputum production, increased adventitious lung sounds, malaise, anorexia, and a decrease in pulmonary function [3, 4, 5].

The majority of pulmonary exacerbations are caused by clonal expansion of existing strains of bacteria, rather than an acquisition of new bugs [6]. Still, other causes of pulmonary distress must be kept on the differential in cystic fibrosis patients. Allergic bronchopulmonary aspergillosis (ABPA) should be suspected in patients with significant wheezing. Though it will likely not be diagnosed in the emergency department [6], it is reasonable to start steroids in these patients as discussed below. Spontaneous pneumothorax can occur, especially in older patients with advanced disease. Recurrence is also common [7].  Minor hemoptysis is also common in CF, especially during a pulmonary exacerbation. Beyond checking the international normalized ratio (INR) to rule out any contributing vitamin K deficiency, this generally only requires reassurance. A complete blood count (CBC) is rarely needed unless in circumstances concerning for anemia.

In patients with suspected pulmonary exacerbations, plain chest radiographs should be ordered to exclude pneumothorax. Other findings such as mucous plugging, peribronchial thickening, and air space disease are common but not specific for an acute exacerbation [8].


Early in life, the most common bugs cultured from the lungs are Staphylococcus aureus and non-typeable Haemophilus influenzae [9]. Pseudomonas aeruginosa is also often isolated early and is the most significant pathogen in CF. Once established, P. aeruginosa is essentially impossible to eradicate due to a combination of genetic adaptations, biofilm formation, and an optimal environment in CF airways.  Burkholderia cepacia complex is less common, but is still occasionally seen and can rapidly lead to necrotizing pneumonia, sepsis, and death. Other common organisms include S. maltophilia, and A. xylosoxidans, which tend to be less virulent.  Aspergillus spp. is isolated from more than 25% of patients but it rarely causes invasive infection outside of the immunocompromised post-transplant patient. However, allergic bronchopulmonary aspergillosis (ABPA) can cause significant illness and it is a diagnosis to keep in mind if your patient presents with significant wheezing [9].


Early recognition and treatment of pulmonary exacerbations has been associated with slower long-term decline in lung function [10]. Pulmonary exacerbations are treated with antibiotics and supportive measures aimed at airway clearance. In cases of ABPA, which is usually not diagnosed in the ED, patients may present with asthma-type symptoms and are usually treated with steroids [9].

Management is summarized in Table 1.

 Table 1

Management Considerations in CF Pulmonary Disease
1. Antipseudomonal antibiotics (high doses): Aminoglycoside + β-lactam

2. Bronchodilator – either MDI or nebulized albuterol

3. Nebulized 7% saline, 4mL

4. BiPAP if needed

5. Only use steroids if there are significant asthma-type symptoms (i.e. wheezing)


In general, antibiotic choices should be tailored to the patient’s previous culture results if known. For mild exacerbations or presumed viral upper respiratory infections not requiring inpatient admission, it is reasonable to discharge patients on an oral antibiotic such as amoxicillin-clavulanate that will cover both H. influenza and S. aureus. If the patient has a known history of Pseudomonas infection, an anti-pseudomonal fluoroquinolone such as ciprofloxacin may be used (1 month – 5 years: 15mg/kg max 750mg/dose BID, 5-18 years: 20mg/kg BID). Recommended duration of treatment is 2 weeks [5]. Patients should continue to use their regular nebulized anti-pseudomonal antibiotic. In these cases, sputum should be sent for culture prior to starting therapy. If there is no improvement on oral antibiotics, there should be a low threshold to admit for intravenous treatment [6].

For more severe exacerbations or those failing outpatient therapy, treatment is usually aimed at Pseudomonas unless the previous cultures identify a different pathogen as the likely culprit. For presumed Pseudomonas infection in a patient with a severe exacerbation, double antibiotic therapy is preferred with two anti-pseudomonal drugs with different mechanisms of action. This is most often accomplished with an aminoglycoside and β-lactam [5]. While results of previous cultures are useful to determine which bug is most likely causing an exacerbation, antibiotic sensitivities for Pseudomonas in particular are not useful for selecting antibiotics and have no effect on patient outcomes [6, 11].

Of the aminoglycosides, tobramycin is most frequently used and has been extensively studied [12, 13]. Amikacin is also used but is used less often. Gentamicin is avoided in CF due to an increased risk of nephrotoxicity [12].  The CF Foundation recommends that aminoglycosides be administered in once daily doses rather than TID to maximize efficacy and minimize nephrotoxicity [3]. Of the β-lactams, ceftazidime is most commonly used among accredited CF centers, followed by cefepime, piperacillin-tazobactam, meropenem, ticarcillin-clavulanate, and aztreonam [14].

Note that patients with CF require larger doses of antibiotics (often larger doses than are FDA-approved) due to a larger volume of distribution, increased renal clearance, and the increased minimal inhibitory concentration (MIC) of Pseudomonas [12, 15]. Many providers, even in CF Foundation-accredited care centers, continue to prescribe inadequate doses of anti-pseudomonal antibiotics despite published dosing guidelines [16]. The best available evidence, based on the pharmacokinetics, pharmacodynamics, tolerability, and efficacy of different regimens, supports the dosing regimens listed below in Table 2 [15].

Table 2 – Antibiotic Choices in CF Exacerbation

Aminoglycoside Dose
Tobramycin 10 mg/kg/day in one daily dose
Amikacin 30-35 mg/kg/day in one daily dose
β-lactam Dose
Ceftazidime 200-400 mg/kg/day div every 6-8 hr (max 8-12 g/day)
Cefepime 150-200 mg/kg/day div every 6-8 hr (max 6-8 g/day)
Pip-tazo 350-600 mg/kg/day div Q4H (max 18-24 g/day piperacillin)
Meropenem 120 mg/kg/day div Q8H
Ticarcillin-clavulanate 450-750 mg/kg/day Q6H (max 24-30 g/day ticarcillin)
Aztreonam 200-300 mg/kg/day div Q6H (max 8-12 g/day)

For infections caused by bugs other than Pseudomonas, culture and susceptibility testing usually guide antibiotic choice. Staphylococcus aureus is a common pathogen in CF and can be treated according to local resistance patterns.  Other typical bugs, notably B. cepacia complex, S. maltophilia, and A. xylosoxidans, tend to be very antibiotic-resistant, so treatment should be guided by culture and susceptibility testing [17].

Patients with CF have variable responses to bronchodilators. Approximately 50% of these patients will have some degree of bronchial hyperresponsiveness [9]. Given the relatively benign side effect profile of beta-agonists, nebulized treatments in the ED may assist in airway opening. Bronchodilators may not be the mainstay of treatment of pulmonary exacerbations, but it is helpful when administered prior to treatment with nebulized hypertonic saline, as discussed below.

Mucolytics (hypertonic saline)

Inhaled hypertonic saline (HS) has been shown to improve the properties of sputum and acutely increase mucociliary clearance in patients with CF. Unlike the other major mucolytic used for CF called DNase I (Dornase alpha), HS appears to be beneficial during an acute exacerbation, especially when followed by chest physiotherapy [9, 10]. A nebulized dose of 4mL of 7% saline has been shown to improve symptoms and lung function when compared to a control treatment with 0.12% saline. Patients treated with the 7% saline nebs during their hospitalization are more likely to return to their pre-exacerbation FEV1 with a number needed to treat of 6 [10]. It is generally well tolerated, but it does have the potential to cause a transient airflow obstruction. For this reason, patients should be treated with a bronchodilator immediately prior to hypertonic saline [18].

Positive pressure ventilation

As in COPD, non-invasive positive pressure ventilation is an attractive treatment option for severe pulmonary exacerbations. Several observational studies have looked at the use of NPPV in these situations and concluded that it may be useful, especially if used early during an acute exacerbation. It is at the very least preferable to invasive ventilation due to the high mortality rates seen in patients with CF who get intubated[19].


Progression of lung disease in CF is largely mediated by chronic inflammation, so it makes sense that corticosteroids should provide some benefit [20].  Unfortunately, although treatment of CF with long-term corticosteroids has shown some improvement in lung function, the risks and significant side effect profile preclude their utility on a regular basis. Theoretically, short-term use of steroids during an acute pulmonary exacerbation should have a more acceptable risk-benefit profile. Only two small studies (n=44) have looked at the use of steroids during an acute exacerbation and showed a small trend towards improvement in lung function at follow up [20, 21]. In the larger of the studies, 3 of the 12 patients in the prednisone group had to be withdrawn from the study either from hypertension or hyperglycemia [20]. The CF Foundation concludes there is insufficient evidence to recommend routine use of steroids during an acute exacerbation [3].  Though they are not recommended for routine use, they may provide more benefit in patients with predominant asthma-type symptoms or suspected ABPA [9]. Close consultation with the patient’s pulmonologist if possible is needed to discuss steroid treatment.

Your patient reports growing Pseudomonas from multiple cultures in the past, so you decide to treat her with cefepime and tobramycin. You also give her an albuterol treatment immediately followed by a 7% saline neb. You had considered BiPAP, but her respiratory rate and work of breathing improve following treatment. She is admitted to the hospital for continued IV antibiotics and airway clearance therapy.

Case 2

A 12 year old male with cystic fibrosis presents with 3 weeks of progressively worsening crampy right lower quadrant (RLQ) abdominal pain and now non-bilious vomiting and oral fluid intolerance. He had a few episodes of diarrhea yesterday but has since had no bowel movement. He takes pancreatic enzyme replacement therapy and has chronic constipation, for which he uses polyethylene glycol (PEG) 3350 daily. His vital signs are normal for his age except for a heart rate of 120 beats per minute (bpm). His examination is significant for dry mucous membranes and abdominal distention with RLQ tenderness, but no rigidity or guarding. You think you feel a small mass in the RLQ. His abdominal x-ray is shown below:


Distal Intestinal Obstruction Syndrome

Distal Intestinal Obstruction Syndrome (DIOS), previously known as “meconium ileus equivalent,” is an entity unique to CF that is caused by partial or complete obstruction of the ileocecum by inspissated fecal material [22]. It is seen in all age groups, though it is more common in adults and is almost always seen in patients with pancreatic insufficiency [23].


DIOS commonly presents with progressive, cramping abdominal pain that usually located in the RLQ or peri-umbilical region. Pain may be acute, but it often precedes the actual obstruction by several weeks or even months. Patients may have abdominal distension first, however.  Though DIOS is commonly seen with constipation, it may also be seen with diarrhea or even normal bowel movements [23]. On examination, the inspissated material can usually be felt in the RLQ, although a palpable mass may be present for years without causing obstructive symptoms [24].


A plain abdominal radiograph is the first line imaging test that should be obtained. It will typically show an accumulation of “bubbly” or “granular” fecal material in the distal ileum [23]. The triad of characteristic abdominal pain, palpable RLQ mass, and distal ileal fecal material on x-ray is usually sufficient to diagnose DIOS. If symptoms or radiographic findings are atypical, or if there is no improvement with treatment, additional imaging such as ultrasound or CT scan should be obtained to evaluate mimics such as appendicitis or intussusception [24].

Differential Diagnosis

It may be difficult to distinguish impending DIOS from chronic constipation by history alone. Constipation usually has a more gradual onset of symptoms with fecal material distributed throughout the colon, as opposed to being localized to the right lower quadrant [22]. However, these entities often coexist and except in severe cases, initial treatment is the same.

Appendicitis should also be on the differential, but unfortunately is sometimes difficult to evaluate. Chronically inspissated mucoid contents may lead to a distended appendix that is difficult to distinguish from an acutely inflamed appendix. This can often lead to a delay in diagnosis of appendicitis, resulting in increased rates of appendiceal perforation and abscess formation in patients with CF.  Other causes of bowel obstruction must also be considered such as adhesions, malignancy, or intussusception. Intussusception occurs in about 1% of CF patients and is a common mimic but can also be a complication of DIOS [24].


First, correct any fluid or electrolyte abnormalities and treat any associated infections. After that, treatment is fairly straightforward and involves laxatives administered either orally, by nasogastric tube, or by enema. Patients with incomplete obstructions usually respond to oral therapy with any PEG bowel prep solution such as GoLytely®, Klean-Prep®, or Movicol®. Another option for oral therapy is Gastrografin diluted in water or juice (50mL in 200mL for kids under 6 years, and 100mL in 400mL for everyone else). Therapy is continued until symptoms resolve and bowel movements are clear. Thus, admission may be required [24].
For patients with complete obstruction, PO intolerance, or failure of oral therapy, a nasogastric tube should be placed for decompression, followed by a Gastrografin enema. Since Gastrografin is radiopaque, these enemas can be both diagnostic and therapeutic and may be used to monitor progress [23, 24, 25]. However, these enemas can cause significant fluid shifts as well as intestinal ischemia, perforation, and necrosis, so they should only be administered by an experienced radiologist. These patients all require admission with a low threshold for surgical consultation [24, 26].
You suspect an incomplete obstruction, but he remains PO intolerant. You place an IV to draw labs and give him a 20 cc/kg bolus of LR. After correcting his electrolytes, you place a nasogastric tube for decompression and to administer GoLytely for bowel irrigation. He has a small bowel movement and slight improvement in pain. He is admitted to pediatrics for continued bowel irrigation.


-CF is not limited to Caucasians and over 33% of cases are missed by newborn screening programs [2].

-Pulmonary exacerbations must be treated early and aggressively to slow the decline in lung function [10].

Treatment of pulmonary exacerbations:

  1. Antipseudomonal antibiotics (high doses): Aminoglycoside + β-lactam
  2. Bronchodilator – either MDI or nebulized albuterol
  3. Nebulized 7% saline, 4mL
  4. BiPAP if needed’
  5. Only use steroids if there are significant asthma-type symptoms (i.e. wheezing)


-Diagnosed by classic history, mass in the RLQ, and localized fecal material on plain abdominal film [22].

-Don’t miss appendicitis or intussusception. Get an ultrasound and/or CT scan if needed [24].

-Correct fluids and electrolytes first [24].

-If PO tolerant, may treat from above with PEG solution (e.g. GoLytely®) or Gastrografin diluted 1:4 in water or juice. Patients may require an NG tube in order to consume enough of the laxative [24].

-If PO intolerant or with bilious vomiting (i.e. complete obstruction), decompress the stomach with a nasogastric tube. Call radiology for a Gastrografin enema [24].

-Treat until bowel movements are clear and watery [24].


References / Further Reading

  1. Rowe SM, Miller S, Sorscher EJ. Cystic Fibrosis. N Engl J Med 2005; 352:1992-2001.
  2. Cystic Fibrosis Foundation Patient Registry: Annual Data Report to the Center Directors, 2014. https://www.cff.org/2014_CFF_Annual_Data_Report_to_the_Center_Directors.pdf/ (Accessed on June 30, 2016).
  3. Flume PA, Mogayzel PJ, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009 Nov 1;180(9):802-8.
  4. Bilton D, Canny G, Conway S, et al. Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros 2011; 10: Suppl. 2, S79-S81.
  5. Smyth A, Elborn JS. Exacerbations in cystic fibrosis: 3 – Management. Thorax 2008; 63: 180-184.
  6. Bhatt JM. Treatment of pulmonary exacerbations in cystic fibrosis. Eur Respir Rev. 2013 Sep 1;22(129):205-16. PMID 23997047.
  7. Flume PA. Pneumothorax in cystic fibrosis. Current Opinion in Pulmonary Medicine 2011. 17(4):220-225.
  8. Greene KE, Takasugi JE, Godwin JD, et al. Radiographic changes in acute exacerbations of cystic fibrosis in adults: a pilot study. Am J Roentgenol 1994; 163(3):557-62.
  9. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis. Am J Respir Crit Care Med 2003; 168:918-951.
  10. Dentice, RL, Elkins MR, Middleton PG, et al. A randomized trial of hypertonic saline during hospitalization for exacerbation of cystic fibrosis. Thorax 2016; 71:141-147.
  11. Hurley MN, Ariff AH, Bertenshaw C, et al. Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis. J Cyst Fibros 2012; 11:288-292.
  12. Talwalkar JS, Murray TS. The Approach to Pseudomonas aeruginosa in Cystic Fibrosis. Clin Chest Med 2016; 37:69-81.
  13. Young DC, Zobell JT, Stockmann C, et al. Optimization of Anti-Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: V. Aminoglycosides. Pediatric Pulmonology 2013; 48:1047-1061.
  14. Fischer DR, Namanny H, Zobell JT. Follow-up survey of the utilization of anti-pseudomonal beta-lactam antibiotics at U.S. cystic fibrosis centers. Pediatr Pulmonol. 2016 Jul; 51(7):668-9.
  15. Zobell JT, Young DC, Waters CD, et al. Optimization of Anti-Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: VI. Executive Summary. Pediatric Pulmonology 2013; 48:525-537.
  16. Zobell JT, Waters CD, Young DC, et al. Optimization of Anti-Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: II. Cephalosporins and Penicillins. Pediatric Pulmonology 2013; 48:107-122.
  17. Doring G, Flume P, Heijerman H, et al. Treatment of lung infection in patients with cystic fibrosis: Current and future strategies. Journal of Cystic Fibrosis 11 (2012):461-479.
  18. Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006; 354:229.
  19. Fauroux B. Why, when and how to propose noninvasive ventilation in cystic fibrosis? Minerva Anestesiol 2011; 77:1108-1114.
    20. Dovey M, Aitken ML, Emerson J, McNamara S, Waltz DA, Gibson RL. Oral corticosteroid therapy in cystic fibrosis patients hospitalized for pulmonary exacerbations: a pilot study. Chest 2007;132:1212-1218.
  20. Tepper RS, Eigen H, Stevens J, Angelicchio C, Kislin J, Ambrosius W, Heilman D. Lower respiratory illness in infants and young children with cystic fibrosis: evaluation of treatment with intravenous hydrocortisone. Pediatr Pulmonol 1997;24:48-51.
  21. Houwen RH, van der Doef HP, Sermet I, et al. Defining DIOS and constipation in cystic fibrosis with a multicenter study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr 2010; 50:38
  22. Houwen RH, van der Doef HP, Sermet I, et al. Defining DIOS and constipation in cystic fibrosis with a multicenter study on the incidence, characteristics, and treatment of DIOS. J Pediatr Gastroenterol Nutr 2010; 50:38.
  23.  Khoshoo V, Udall JN Jr. Meconium ileus equivalent in children and adults. Am J Gastroenterol 1994; 89(2): 153.
  24. Colombo C, Ellemunter H, Houwen R, et al. Guidelines for the diagnosis and management of distal intestinal obstruction syndrome in cystic fibrosis patients. J Cyst Fibros 2011; 10 Suppl 2:S24.
  25. Nash EF, Ohri CM, Stephenson AL, and Durie PR. Abdominal pain in adults with cystic fibrosis. European Journal of Gastroenterology & Hepatology 2014, 26:129-136.
  26. Voynow JA, Mascarenhas M, Kelly A, Scanlin TF. Cystic Fibrosis. In: Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AI, Senior RM, Siegel MD. Eds. Fishman’s Pulmonary Diseases and Disorders, Fifth Edition. New York, NY: McGraw-Hill; 2015. http://accessmedicine.mhmedical.com/content.aspx?bookid=1344&Sectionid=81189522. Accessed August 06, 2016.

Bi-level Ventilation: Who Needs it and Who Doesn’t? Pearls and Pitfalls

Authors: Robert Goodnough, MD (EM Resident Physician, UCSF-ZSFG Emergency Medicine Residency Program), Karla Canseco, MD (EM Resident Physician, UCSF-ZSFG Emergency Medicine Program), and Marianne Juarez, MD (Assistant Clinical Professor of Emergency Medicine, UCSF-ZSFG Medical Center) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)


A 65 year-old presents to the emergency department (ED) via emergency medical services (EMS) due to respiratory distress that awakened him from sleep. EMS reports that, upon their arrival, the patient had an oxygen saturation of 85% on room air. Continuous positive airway pressure (CPAP) was provided to the patient and his oxygen saturation improved to 94%. The CPAP also improved the patient’s work of breathing.

On examination in the ED, the patient is tachypneic. He also demonstrates rales, supraclavicular retractions, and is in atrial fibrillation with heart rate (HR) in the 110s. His blood pressure (BP) is 205/104 mmHg.  A nitroglycerin drip is ordered and respiratory therapy is called to place the patient on bi-level positive airway pressure (BiPAP). At this point, one of your seasoned colleagues mentions that he remembered a time when all heart failure patients were intubated.

You tuck your endotracheal (ET) tube into your back pocket and you wonder if your patient will eventually need this…


Noninvasive Positive Pressure Ventilation (NIPPV) is mechanical ventilation that is provided via nasal prongs, a full or oral-nasal facemask, or mouthpiece.  Different modes of mechanical ventilation are available, but the most commonly used methods are CPAP and BiPAP1.  The majority of evidence in NIPPV does not differentiate between CPAP and bi-level, or other modes of NIPPV, and the majority of outcomes and data are applied to NIPPV as a generalized intervention.


(photo courtesy of Kai Romero, MD)

Why avoid endotracheal intubation?

Endotracheal intubation is a life-saving intervention when applied skillfully, but its attendant risks are well described.  Staving off intubation has been shown to decrease complications such as hypotension, arrhythmias, death, and nosocomial infections. Intubation also places patients at an increased need for sedation and invasive procedures2. Noninvasive ventilation has become commonplace in the ED to treat respiratory failure and prevent intubation1.

Some Definitions:

  • CPAP: applies constant pressure throughout the breathing cycle to increase functional residual capacity (FRC) by recruiting alveoli, decreasing work of breathing, and improving oxygenation. It is best given in hypoxemic patients 1,3.
  • PEEP/EPAP: Positive End Expiratory Pressure, which is the alveolar pressure before inspiratory flow begins. Adding PEEP helps decrease the amount of work required to initiate a breath. It also helps to decrease atelectasis1,4.
  • Bi-level: Cycled ventilation between Inspiratory Positive Airway Pressure (IPAP) and Expiratory Positive Airway Pressure/PEEP1BiPAP supports ventilation and increases oxygenation.
  • Pressure Support: The difference between EPAP and IPAP is referred to as pressure support. Pressure support makes it easier to draw larger tidal volumes1,4.

Applications for NPPV/Bi-level

1. Chronic Obstructive Pulmonary Disease (COPD)

In COPD, acute respiratory failure manifests as hypoxic, hypercapneic respiratory failure with collapse of small airways. Hyperinflation also occurs. Acute respiratory failure from COPD leads to increased work of breathing, acidosis, altered mental status, and ultimately coma, decompensation, and death5

Bi-level ventilation is a primary treatment option in COPD with good evidence for success5. When compared to usual medical care, bi-level ventilation decreases the risk of death (relative risk reduction 48%) and intubation rates (RRR 60%)5.

Number Needed to Treat (NNT) for mortality benefit = 10

NNT to prevent intubation = 4

Furthermore, when comparing patients with moderate and severe acidosis, bi-level ventilation decreased mortality, rates of intubation, and lengths of stay. It also improved work of breathing, acidosis, and PaC02 levels. Finally, regarding these outcomes, there were no significant differences between more and less acidotic patients at admission5,6.

Indications for NIPPV/bi-level ventilation6

1.      pH <7.35or PaC02 >45 mmHg

2.      Severe dyspnea with signs of increased work of breathing

3.      Caution: In severe respiratory acidosis (pH <7.25), failure rates of NIPPV may be as high as 50%1

Common Initial Settings:

  • IPAP 8-20 cm H2O (up to 30 cm H20)
  • EPAP 2-6 cm H2O to overcome intrinsic airway collapse3,5,7
  • Begin with either high IPAP and then titrate down, or low and titrate high. Both are reasonable, but require close monitoring to meet ventilation goals.7 Each patient is different.
  • Endpoints for physiologic improvement:  at 1 hour, reassessment should be made. Decisions regarding treatment failure, worsening clinical status of bi-level should be made early.5

2. Cardiogenic Pulmonary Edema (CPO)

Acute cardiogenic pulmonary edema is a common and potentially fatal cause of acute respiratory distress. CPO is related to a critical interaction between worsening left ventricular systolic function and an acute increase in systemic vascular resistance that results in rapid accumulation of fluid in the interstitium of the lung. This leads to decreased lung compliance, increased airway resistance, hypoxia, decreased diffusion capacity, and hypercarbia from muscle fatigue8.

Bi-level offers the advantage of improving both cardiac and pulmonary function by providing pressure support with IPAP and EPAP/PEEP. IPAP assists ventilation, which decreases the work of breathing and assures adequate ventilation. The EPAP/PEEP increases the FRC by recruiting collapsed alveoli, improving oxygenation, and helping to force interstitial fluid back into the pulmonary vasculature9,10.

Bi-level ventilation also increases intrathoracic pressure, which can lead to decreased left ventricular (LV) end diastolic volume. This results in decreased afterload and increased LV ejection fraction/stroke volume. Thus, the heart muscle is stretched less, and placed at a steeper part of the Starling curve. This results in stronger LV contractions, and reductions in BP and HR11.


(Figure: in the failing heart, NIPPV both decreases preload and also shifts the Starling curve (decreases afterload) to augment cardiac performance)12,13

Common Initial Settings:

·         IPAP: 10 to 20 cm H20

·         EPAP: 5 to 10 cm H20

·         I:E ratio of IT to ET and is usually set at 1:3 or 1:4 (Inspiratory to Expiratory ratio)

Evidence for Bi-level ventilation in CPO:

Unfortunately, most of the evidence for NIPPV for CPO is centered on CPAP with few trials comparing the two modalities (CPAP and bi-level) head-to-head.

In a Cochrane review looking at NIPPV in CPO, CPAP alone has been proven to decrease intubation rates and to decrease in-hospital mortality, without the same benefit seen using bi-level ventilation14.

In the treatment of CPO, controversy regarding the safety of bi-level ventilation stems mainly from a single small study comparing the two NIPPV modalities. This study showed a more rapid improvement in vital signs, dyspnea and arterial blood gas (ABG) results with bi-level, but it also showed higher rates of myocardial infarction (MI) with bi-level ventilation15.  However, subsequent trials comparing CPAP and bi-level showed no difference in MI rates, but decreased intubation rates for those treated with bi-level, especially in patients presenting with hypercarbia16,17.

A trend that holds true is that bi-level leads to rapid improvement in physiological parameters such as respiratory rate, pH, PaCO2, PaO2, HR, work of breathing, afterload, preload, cardiac index, and ejection fraction. However,  more studies need to be performed to show a clear benefit in patient mortality and consistently decreased intubation rates18–21.

Indications for NIPPV in CPO:

1.      Increased work of breathing

2.      Hypercapnia and respiratory failure

3. Asthma

In asthma, NIPPV/bi-level ventilation might help to overcome intrinsic auto-PEEP, to decrease ventilation/perfusion (V/Q) mismatch by increased recruitment of alveoli, and to have a direct bronchodilatory effect in order to decrease work of breathing22.

In the mechanical ventilation of an asthmatic, one should carefully weigh the risk of critical error if the patient is not allowed a prolonged period of expiration in order to prevent “auto-PEEP”. Auto-PEEP is a condition where inhaled breaths are progressively delivered to lungs that have not returned to their FRC. This can subsequently lead to life-threatening hypotension and severe barotrauma, such as pneumothorax2.

Complications from intubation in a severe asthmatic can be severe, including cardiovascular collapse, pneumothorax, and prolonged intubation23.  However, a systematic review comparing NIPPV to medical care did not find a significant benefit to mortality or decreased rates of intubation, though these end points were likely limited by small numbers of patients studied in the intervention22.

Given the risks of intubation, and the purported physiologic benefits of bi-level ventilation to a severe asthmatic, NIPPV is a reasonable treatment strategy.  However, this should be done in tandem with medical management in carefully selected and monitored patients. Of note, NIPPV in asthma has not yet achieved the standard of care.

Indications for NIPPV in Asthma:

1.      As a carefully applied adjunct to medical management in refractory asthma

4. Acute Respiratory failure (no pre-existing chronic lung disease)

The benefits of NIPPV is not clear in undifferentiated acute respiratory failure and the evidence is often conflicting.  The use of NIPPV in undifferentiated acute respiratory failure (ARF) has shown similar mortality rates to conventional ventilation, but it has also demonstrated decreased intubation rates. On the other hand, decreased intubation rates may not apply to those with pneumonia or non-hypercapneic respiratory failure (PNA)24.

A recent multi-center trial showed no decrease in intubation rates for non-hypercapneic ARF (64% PNA) in those without chronic lung disease when compared to high flow or regular oxygen. Additionally, 90 day mortality was decreased in the high flow oxygen group compared to NIPPV. Also, delayed intubation via NIPPV did not show an association with increased mortality25.

Method of delivery and severity of illness likely affect mortality rates in patients with adult respiratory distress syndrome (ARDS) treated with NPPV, as a recent RCT showed decreased 90 day mortality in patients ventilated with helmeted NPPV compared to face mask NPPV26.


1.      There are no clearly recommended indications and it should be on a case by case basis.

5. Blunt Thoracic Trauma

In a recent meta-analysis of 219 patients with thoracic trauma, NIPPV decreased intubation rates, improved oxygenation, decreased infection rates and showed mortality rates of 3% vs 22.9% in “standard management,” which was CPAP or face mask oxygen27.

6. Special Populations:

NIPPV decreases intubation rates and in-hospital mortality when applied to acute hypoxic respiratory failure in immunocompromised patients1,28.

It may also provide a benefit to patients with palliative care needs in whom endotracheal intubation is not within their goals of care, with some studies showing reversal of acute respiratory failure and return to home1,28,29.

The use of NPPV in the ARF of decompensation of neuromuscular disease is controversial, and may not be indicated in those with rapidly progressive disease29.

Pre-oxygenation For Intubation:

Much of the focus has been on avoiding intubation, but in critically ill patients, intubation and mechanical ventilation can be life-saving; to intubate an unstable patient is perilous, with desaturation, arrhythmia, cardiovascular collapse and cardiac arrest as well recognized entities30.

Pre-oxygenation prior to intubation is the standard of care to prevent life threatening complications during intubation.  Some patients display refractory hypoxia in the face of usual facemask pre-oxygenation, and failure to reach 93-95% Sp02 prior to intubation places the patient at risk for desaturation and apnea during the procedure31.

NIPPV has been shown to decrease desaturation rates in refractory hypoxia during pre-oxygenation for intubation and should be strongly considered for pre-oxygenation prior to intubation in refractory hypoxia30–32.


  1. Positive Pressure is not everything. Do not forget medical management
  2. Bi-level ventilation is an early “go-to” in moderate to severe COPD exacerbations
  3. Experienced respiratory therapists (RTs) and staff are critical to the success of non-invasive ventilation
  4. Once applied, reassess your patient frequently and be ready to adjust!
  5. Can be used to stave off intubation at the end of life
  6. Consider for pre-oxygenation prior to intubation


  1. Positive pressure can cause hypotension and decompensation if blindly applied
  2. Do not place a pressure mask on a damaged face or a fluid filled mouth
  3. Do not delay necessary intubation
  4. Do not let your patient Auto-PEEP
  5. Your severely acidotic patient is at high risk for failure: be ready to intubate.
  6. If your patient is not awake, then the patient should be intubated.

 Who Needs It?

  1. Patients with moderate to severe COPD exacerbations
  2. Those patients with cardiogenic pulmonary edema with increased work of breathing or hypercapnia
  3. Patients with isolated blunt thoracic trauma
  4. The immunocompromised patient with hypoxic respiratory failure
  5. Patients who require pre-oxygenation prior to intubation

Who Does Not?

  1. Altered Mental Status
  2. Facial Trauma/Can’t Handle their own secretions

Gray Zones?

  1. Asthma
  2. Neuromuscular Disease
  3. Undifferentiated Hypoxic Respiratory Failure

References / Further Reading

1. Aboussouan, L. S. & Ricaurte, B. Noninvasive positive pressure ventilation: Increasing use in acute care. Cleve. Clin. J. Med. 77, 307–316 (2010).

2. Leatherman, J. Mechanical ventilation for severe asthma. Chest 147, 1671–1680 (2015).

3. Bolton, R. & Bleetman, A. Non-invasive ventilation and continuous positive pressure ventilation in emergency departments: where are we now? Emerg. Med. J. EMJ 25, 190–194 (2008).

4. Appendini, L. et al. Physiologic effects of positive end-expiratory pressure and mask pressure support during exacerbations of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 149, 1069–1076 (1994).

5. Ram, F. S. F., Picot, J., Lightowler, J. & Wedzicha, J. A. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. CD004104 (2004). doi:10.1002/14651858.CD004104.pub2

6. Pauwels, R. A., Buist, A. S., Calverley, P. M. A., Jenkins, C. R. & Hurd, S. S. Global Strategy for the Diagnosis, Management, and  Prevention of Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 163, 1256–1276 (2001).

7. Prinianakis, G., Delmastro, M., Carlucci, A., Ceriana, P. & Nava, S. Effect of varying the pressurisation rate during noninvasive pressure support ventilation. Eur. Respir. J. 23, 314–320 (2004).

8. Wiesen, J., Ornstein, M., Tonelli, A. R., Menon, V. & Ashton, R. W. State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock. Heart Br. Card. Soc. 99, 1812–1817 (2013).

9. Cross, A. M. Review of the role of non-invasive ventilation in the emergency department. J. Accid. Emerg. Med. 17, 79–85 (2000).

10. Peter, J. V., Moran, J. L., Phillips-Hughes, J., Graham, P. & Bersten, A. D. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Lancet Lond. Engl. 367, 1155–1163 (2006).

11. Sheldon, R. Congestive heart failure and noninvasive positive pressure ventilation. Emerg. Med. Serv. 34, 64–67 (2005).

12. Figueroa, M. S. & Peters, J. I. Congestive heart failure: Diagnosis, pathophysiology, therapy, and implications for respiratory care. Respir. Care 51, 403–412 (2006).

13. Shekerdemian, L. & Bohn, D. Cardiovascular effects of mechanical ventilation. Arch. Dis. Child. 80, 475–480 (1999).

14. Vital, F. M. R., Ladeira, M. T. & Atallah, A. N. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst. Rev. CD005351 (2013). doi:10.1002/14651858.CD005351.pub3

15. Mehta, S. et al. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit. Care Med. 25, 620–628 (1997).

16. Nava, S. et al. Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. Am. J. Respir. Crit. Care Med. 168, 1432–1437 (2003).

17. Gray, A. J. et al. A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial. Health Technol. Assess. Winch. Engl. 13, 1–106 (2009).

18. Park, M. et al. Oxygen therapy, continuous positive airway pressure, or noninvasive bilevel positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema. Arq. Bras. Cardiol. 76, 221–230 (2001).

19. Crane, S. D., Elliott, M. W., Gilligan, P., Richards, K. & Gray, A. J. Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema. Emerg. Med. J. EMJ 21, 155–161 (2004).

20. Levitt, M. A. A prospective, randomized trial of BiPAP in severe acute congestive heart failure. J. Emerg. Med. 21, 363–369 (2001).

21. Pang, D., Keenan, S. P., Cook, D. J. & Sibbald, W. J. The effect of positive pressure airway support on mortality and the need for intubation in cardiogenic pulmonary edema: a systematic review. Chest 114, 1185–1192 (1998).

22. Ram, F. S. F., Wellington, S., Rowe, B. & Wedzicha, J. A. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst. Rev. CD004360 (2005). doi:10.1002/14651858.CD004360.pub3

23. Landry, A., Foran, M. & Koyfman, A. Does Noninvasive Positive-Pressure Ventilation Improve Outcomes in Severe Asthma Exacerbations? Ann. Emerg. Med. 62, 594–596

24. Honrubia, T. et al. Noninvasive vs conventional mechanical ventilation in acute respiratory failure : A multicenter, randomized controlled trial. Chest 128, 3916–3924 (2005).

25. Frat, J.P. et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N. Engl. J. Med. 372, 2185–2196 (2015).

26. Patel, B. K., Wolfe, K. S., Pohlman, A. S., Hall, J. B. & Kress, J. P. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA 315, 2435–2441 (2016).

27. Chiumello, D., Coppola, S., Froio, S., Gregoretti, C. & Consonni, D. Noninvasive ventilation in chest trauma: systematic review and meta-analysis. Intensive Care Med. 39, 1171–1180 (2013).

28. Hill, N. S., Brennan, J., Garpestad, E. & Nava, S. Noninvasive ventilation in acute respiratory failure. Crit. Care Med. 35, 2402–2407 (2007).

29. Mas, A. & Masip, J. Noninvasive ventilation in acute respiratory failure. Int. J. Chron. Obstruct. Pulmon. Dis. 9, 837–852 (2014).

30. Mosier, J. M. et al. The Physiologically Difficult Airway. West. J. Emerg. Med. 16, 1109–1117 (2015).

31. Weingart, S. D. & Levitan, R. M. Preoxygenation and prevention of desaturation during emergency airway management. Ann. Emerg. Med. 59, 165–175.e1 (2012).

32. Baillard, C. et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am. J. Respir. Crit. Care Med. 174, 171–177 (2006).


Post-Intubation Complications in ED Setting

Authors: Summer Chavez, DO, MPH (EM Resident Physician, Virginia Tech-Carilion) and Timothy Fortuna, DO (EM Attending Physician, Virginia Tech-Carilion) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, SAUSHEC EM, USAF)

It’s a busy Friday night when EMS calls with reports of a 74 year-old female nursing home patient that is altered, hypotensive with a blood pressure of 84/56 and hypoxic on 15 L oxygen by non-rebreather with saturations of 87%. They are three minutes away. You gulp down the rest of your energy drink when a transfer from another hospital comes in, a 62 year-old male with subarachnoid hemorrhage on Coumadin. “You might want to take a look at this,” the nurse remarks as stretcher rolls by. Just then, another call goes out over the intercom – “Zero minute trauma alert by ground.” There’s a high likelihood that all of these patients will need to be intubated. How do these medical conditions affect these patients’ intubations and post-intubation care? What troubleshooting can you do in case of persistent hypoxia after intubation?

Peri-Intubation Hypotension & Cardiac Arrest

Peri-intubation cardiac arrest is defined as cardiac arrest that occurs 60 minutes after starting airway management.1 About two-thirds of post-intubation cardiac arrests happen within 10 minutes.1 Peri-intubation cardiac arrest is more likely in patients that were hypotensive or hypoxic before intubation.1 Furthermore, these patients are 14 times more likely to die in the hospital.1 Before intubating the patient, if they are hypotensive, consider fluid resuscitation or pressors to maintain the patient’s blood pressure. Push dose pressors may help to temporize the gap between pre- and post-intubation.

– Epinephrine is the ideal push dose pressor to use in the emergency department – it increases cardiac output and causes vasoconstriction, leading to an improvement in MAP.2 To create push dose epinephrine, pull up 1 mL of 1:10,000 epinephrine, the same concentration used in cardiac arrest, followed by 9 mL of normal saline in the same syringe.3 10 mcg of epinephrine is now in every 1 mL of solution.3 Mix vigorously. While vasopressors can be given safely in peripheral lines, monitor for infiltration at the IV site.3 Administer 0.5-2 mL (5-20 mcg) of solution every 1-5 minutes as needed for effect.4

– Phenylephrine has pure alpha agonist effects.4 If phenylephrine is not available in premixed syringes, push dose phenylephrine can be created at bedside. Use a 3 mL syringe to pull up 1 mL of phenylephrine in a 10 mg/mL concentration and mix into a 100 mL bag of normal saline.4 There is now 100 mL of phenylephrine at 100 mcg per mL. Phenylephrine is administered at 0.5-2 mL (50-200 mcg) every 1-5 minutes as needed.4 Push dose pressors are useful adjuncts in managing hypotension, but it is also important to discuss why positive pressure ventilation causes hypotension.

Normally when we breathe, air is being pulled into our lungs. When someone is intubated with positive pressure ventilation, air is physically pushed into the lungs. Essentially, preload is decreased, leading to a corresponding decrease in cardiac output and blood pressure. Positive-pressure ventilation reduces the pressure differential for venous return.5 During diastole, it also lowers the transmural pressure causing a drop in ventricular filling.5 Finally, positive pressure ventilation causes the resistance in the pulmonary vasculature to increase, which can cause the right ventricle to dilate and obstruct the left ventricle from filling – ventricular interdependence.5

Post-Intubation Hypoxia

Many times patients are intubated for increased work of breathing, altered mental status, or hypoxia. What do you do when the patient remains hypoxic after intubation or suddenly becomes hypoxic? The underlying problem may be related to displacement of the tube, obstruction, pneumothorax, pulmonary embolism, pulmonary edema, pneumonia, equipment malfunction and stacked breaths6. Scott Weingart discusses the DOPES mnemonic on EmCrit.6

Capnometry is an excellent method for determining tube placement. For patients not in cardiac arrest, the colorimetric CO2 detector has been shown to detect the endotracheal tube in the esophagus in 100% of cases and in 99% of the time, when the tube was in the trachea.5 End-tidal carbon dioxide capnography is becoming increasingly more common in emergency departments across the country. End-tidal PCO2 is a non-invasive marker of arterial PCO2.5 A baseline should be established between the PaCO2 and PETCO2 gradient. This will remain constant unless a process exists that disrupts gas exchange.5 With an increase in the difference between PaCO2 and PETCO2 or sharp fall in end-tidal CO2, think about pulmonary embolism, pneumonia, pulmonary edema, mainstem intubation, excessive tidal volumes. or PEEP causing alveoli to over expand.5

Obstruction, especially a mucus plug, can cause sudden desaturation. To remove a mucus plug, use a suction catheter.6 As mentioned earlier, pneumothorax, pulmonary embolism and pulmonary edema are other causes to think about.6,7 These can be evaluated with physical exam, chest x-ray, or bedside ultrasound. In the event of an equipment failure, disconnect the ventilator and ventilate the patient using a bag-valve mask. This should be the first step.7 Especially in patients with asthma who may be prone to auto-PEEP through breath stacking, disconnecting the ventilator and pushing down on the chest can help to relieve some of the pressure.

D isplacement
O bstruction
P neumothorax

ulmonary embolism

ulmonary edema


E quipment
S tacked breaths


Post-Intubation Sedation & Analgesia

Failing to obtain adequate sedation and pain control after intubating a patient is a common mistake. There are certain combinations of sedation and analgesia that may be more beneficial in particular scenarios. Before describing these clinical settings, let’s briefly review the different medications.


Propofol is a lipophilic anesthetic that is a global CNS depressant.8 The onset of action for a bolus is approximately 30 seconds with a duration of approximately 3-10 minutes depending on the administration.8 For long term use, such as in the ICU, propofol tends to accumulate. Hypotension, as much as a 30% reduction in MAP, can be observed, more so in those who are hypovolemic. For sedation after intubation, start dosing at 5-50 mcg/kg/min IV gtt.5 In the elderly, doses may be reduced by approximately 20%.8


Fentanyl is an anesthetic that acts within the CNS to increase the pain threshold and alter pain perception. When given by IV, the effects are almost immediate, but still takes a few minutes to reach maximum effects.9 One of the benefits of using fentanyl is that it does not cause as much histamine release as morphine, therefore it is less likely to cause hypotension and has few adverse hemodynamic effects.5 Fentanyl lasts about 30 minutes to 1 hour.9 For post-intubation sedation, Fentanyl should be dosed at 1-3 mcg/kg/hr IV gtt.10


Versed (Midazolam) is a benzodiazepine that acts on postsynaptic GABA receptors. By binding at this site, it increases the inhibitory effect of GABA. When given IV, it has an onset of action within 1-5 minutes with a peak effect within 30 to 60 minutes. In patients with renal failure, the drug is more likely to accumulate. In the elderly or chronically ill, reduce the dosages by roughly 20-50%. Induction doses for patients that are unpremedicated: dose at 0.3-0.35 mg/kg; for premedicated patients: dose at 0.05-0.2 mg/kg. Maintenance dosing should start at 20-100 mcg/kg/hr IV gtt.10


Ketamine is a dissociative agent that blocks glutamate through its actions as a NMDA receptor antagonist.11 When given IV, onset of action is 30 seconds with a duration of 1-2 hours.5 One of the side effects of ketamine is hypersalivation. In the past, there were concerns regarding increases in intracranial pressure due to ketamine. The rationale was a sympathetic stimulation could cause ICP to increase, worsening a patient’s condition.12 A review of 10 trials involving intubated ICU patients concluded that ketamine had no harmful effects on patient outcomes including neurologic endpoints and mortality.12,13 Two of the trials in the review involved patients with traumatic brain injury determined there was no difference in cerebral perfusion pressure and daily ICP.12 With this in mind, some authors continue to recommend refraining from using ketamine in patients with HTN and increased ICP.12 Initial bolus for ICU patients is 0.1-0.5 mg/kg with maintenance dosing 0.05-0.4 mg/kg/hour.14 For those with hypotension this may be a good choice. It also produces some bronchodilation and may be useful in cases of bronchospasm, such as asthma or COPD.12

Now that we have briefly reviewed the medications, let’s go over certain combinations of medications:

For the hypotensive medical patient, such as an elderly nursing home patient with sepsis secondary to urinary tract infection, Fentanyl is a good starting point.15 If the patient remains hypotensive after initial fluid resuscitation, start pressors. In the case of the trauma patient that is hypotensive, use of Fentanyl and/or Ketamine is recommended.15 The 62 year-old male with subarachnoid hemorrhage described earlier in the clinical vignette would benefit from Fentanyl and Propofol.15 Propofol is useful in these cases because of its hemodynamic effect of lowering blood pressure. In the case of a patient with delirium tremens requiring intubation, maximize the use of benzodiazepines in the pre-intubation period.15 Propofol and fentanyl are recommended for post-intubation analgesia/sedation.15 Finally, for patients in status epilepticus, fentanyl and propofol, which has anticonvulsant properties, are suitable choices.


  • Maximize resuscitation of the hypotensive patient in the pre-intubation period. Fluids and vasopressors may be necessary. Don’t underestimate the effect of preload in causing hypotension.
  • When evaluating a patient with sudden hypoxia, think about DOPES. Disconnect the ventilator and manually ventilate with a bag-valve-mask. Push on the chest to allow any trapped air to leave. Suction the endotracheal tube. If none of these things resolve the hypoxia, think about the Ps – pulmonary embolism, pneumothorax, pneumonia, pulmonary edema.
  • There are several different medications you can use for post-intubation sedation and analgesia. Think about what the underlying problem is and the hemodynamic effects of the sedative.

References / Further Reading:

  1. Heffner AC, Swords DS, Neale MN, Jones AE. Incidence and factors associated with cardiac arrest complicating emergency airway management. Resuscitation 2013;84(11):1500–4.
  2. Herget-Rosenthal S, Saner F, Chawla LS. Approach to Hemodynamic Shock and Vasopressors. Clin J Am Soc Nephrol 2008;3(2):546–53.
  3. William Selde, MD. Push Dose Epinephrine as a Temporizing Measure for Drugs Causing Hypotension [Internet]. JEMS J. Emerg. Med. Serv. 2014 [cited 2016 Apr 4]; Available from: http://www.jems.com/articles/print/volume-39/issue-9/features/push-dose-epinephrine-temporizing-measure-0.html
  4. Weingart S. Push-dose pressors for immediate blood pressure control. Clin Exp Emerg Med 2015;2(2):131–2.
  5. Marino PL. Marino’s The ICU Book: Print + Ebook with Updates. Fourth, North American Edition edition. LWW; 2013.
  6. Weingart S. Ventilator checklist for the coding asthmatic [Internet]. EMCrit. 2009 [cited 2016 Mar 17]; Available from: http://emcrit.org/podcasts/finger-thoracostomy/
  7. Man versus machine – post-intubation hypoxia [Internet]. LITFL Life Fast Lane Med. Blog. 2010 [cited 2016 Mar 17]; Available from: http://lifeinthefastlane.com/pulmonary-puzzle-012/
  8. Propofol [Internet]. Access Emerg. Med. [cited 2016 Mar 28]; Available from: http://accessemergencymedicine.mhmedical.com/drugs.aspx?gbosID=131853
  9. Fentanyl [Internet]. Access Emerg. Med. [cited 2016 Mar 28]; Available from: http://accessemergencymedicine.mhmedical.com/drugs.aspx?gbosID=131270
  10. Sandra Thomasian, Joel Schofer, editors. Emergency Medicine Survival Guide. American Academy of Emergency Medicine Resident and Student Association; 2011.
  11. Midazolam [Internet]. Access Emerg. Med. [cited 2016 Mar 28]; Available from: http://accessemergencymedicine.mhmedical.com/drugs.aspx?gbosID=131613
  12. Caro, David. Sedation or induction agents for rapid sequence intubation in adults [Internet]. Date. 2016; Available from: http://www.uptodate.com/contents/sedation-or-induction-agents-for-rapid-sequence-intubation-in-adults#H21
  13. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NGW, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med 2015;65(1):43–51.e2.
  14. Ketamine [Internet]. Access Emerg. Med. [cited 2016 Mar 28]; Available from: http://accessemergencymedicine.mhmedical.com/drugs.aspx?gbosID=131468
  15. Weingart S. Post-intubation Sedation in the Emergency Department [Internet]. EMCrit. 2010 [cited 2016 Mar 17]; Available from: http://emcrit.org/podcasts/post-intubation-sedation/

Diffuse Alveolar Hemorrhage in the ED: Pearls & Pitfalls

Authors: Sumir Shah, DO, MS (EM Resident Physician, University at Buffalo), Eric Cioe, MD, MPH (Director of Global Health, Staten Island Univ Hospital), and Julie Endrizzi, MD (EM Resident Physician, Univ of Rochester) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)


A 45-year-old male with a past medical history of hypertension and a prior gunshot wound presents to your emergency department (ED) with non-radiating, mid-sternal, pleuritic chest pain. The patient also complains of a cough, tactile fever, diaphoresis and chills that started earlier in the morning. He states that he was worried by the specks of red in his otherwise yellow phlegm. The patient admits to marijuana (THC) use, but denies any other illicit drug or alcohol use. He also denies loss of consciousness, seizures, dysuria, or any other symptoms. Emergency Medical Services (EMS) reports that he was given 324mg of aspirin (ASA) en route.

Vital signs upon ED arrival:  Blood pressure (BP) 122/81, Pulse (P) 110, Respiratory Rate (RR) 18, Temperature (T) 35°Celsius (C), and Oxygen saturation (SpO2) 96% on room air.

On exam, the patient is diaphoretic and has diffuse bilateral rales in all lung zones. The remainder of the exam is unremarkable. Laboratory tests demonstrate a white blood cell (WBC) count of 36.4, a hemoglobin (Hgb) of 13.1, and a lactate of 2.9. Urinalysis shows 1+ ketones, 2+ blood, 2+ WBC, 1+ bacteria, 1+ squamous epithelial cells, and a protein of 30. Urine toxicology is positive for THC and cocaine.

The patient is sent for a chest x-ray (CXR), followed by a computed tomography (CT) scan of the chest, showing findings similar to below:

Pic 1 DAHPic 2 DAH

Figure A                                                      Figure B

Figure A: CXR showing new diffuse ground glass opacification of the bilateral lungs, with tiny centrilobular nodules.

Figure B: CT Chest showing diffuse bilateral alveolar ground glass opacities with inter- and intralobular thickening.


Diffuse alveolar hemorrhage (DAH) is a life-threatening medical emergency that is associated with pulmonary disease, bronchial disease and/or trauma. DAH is characterized by bleeding of the pulmonary microvasculature into the alveoli. It is imperative to understand this pathophysiology as many clinical findings are nonspecific and thus, the diagnosis may be difficult to ascertain. (2,7)

DAH is characterized by 3 distinct histological types: Pulmonary Capillaritis, Bland Damage, and Diffuse Alveolar Damage. (9) The most common, Pulmonary Capillaritis, is defined as neutrophilic predominant infiltration of the alveolar septa leading to fibrinoid necrosis of the alveolar and capillary walls. This occurs because the neutrophils undergo cell damage, which causes accumulation of debris, and toxic radicals that undermine the integrity of the cell wall. (6) Drugs such as hydralazine, propylthiouracil (PTU), and carbimazole can trigger this process, but it can also occur due to a number of vasculitides. (8)

The second histologic type of damage is known as Bland Damage. (9) In this subtype, the RBCs leak into the alveoli without histologic findings of inflammation or destruction. This is associated with many of the same diseases that cause capillaritis, such as thrombocytopenia and Anti-GBM (Goodpasture’s) disease, but is also associated with mitral valve pathology. (3,8)

The final subtype of DAH is Diffuse Alveolar Damage. This subtype is defined as edema of the alveolar septa and by formation of hyaline membranes that line the alveolar spaces. (6) This subtype tends to be the most familiar as it encompasses Acute Respiratory Distress Syndrome (ARDS). ARDS has a variety of causes that range from infection to crack cocaine use. (1)

Back to the Case…

Our patient was believed to have presented with his symptoms due to acute crack cocaine ingestion. Cocaine, the most common toxic cause of DAH, is a popular drug in the United States (US). The Drug Abuse Warning Network (WARN) estimates the prevalence is at or above 1.2% in Americans. It is also estimated that 25-60% of users develop respiratory symptoms, known as crack lung, within the first 48 hours. Symptoms of crack lung can range from shortness of breath (SOB) and cough to acute lung injury, ARDS or barotrauma. These symptoms can be further exacerbated in asthma patients because bronchoconstriction commonly occurs. (8,5,10)

Pearl: The most common adulterants of cocaine include the anti-fungal Levamisole and the beta adrenergic agonist Clenbuterol. These have been associated with agranulocytosis, hyperglycemia and hypokalemia. (8)

Pic 3 DAH

Clinical Presentation

The clinical presentation of these patients is often non-specific. It is important to consider the symptoms, imaging, and labs as a group to come to the most accurate diagnosis. Most commonly, patients will present with cough, dyspnea, fever, and hemoptysis. The examination is frequently nonspecific and will most likely consist of diffuse rales or crackles in all lung fields. (2,5)

Pearl: 33% of DAH patients present without hemoptysis due to the large absorptive capacity of the lungs. (9)


In general, cough, dyspnea, hemoptysis, and a positive bronchoalveolar lavage (BAL) for RBCs is enough to establish the diagnosis of DAH. (7) However due to the non-specific nature of the clinical symptoms it is also important to consider the patient’s past medical history for recent infections, drug use, toxic exposures, and known co-morbidities such as systemic vasculitis or mitral valve disease. These can all be used as clues to identify a cause.

Chest x-ray will show patchy alveolar infiltrates similar to pulmonary edema, however there will likely not be any Kerley-B lines, pleural effusions, or peri-bronchial cuffing. Ground-glass opacities and interlobular thickening may be seen on high resolution CT scan of the chest. (4,8)

Pearl: RBC-tagged nuclear imaging is of limited usefulness in diagnosing DAH. (8)

Although laboratory studies on their own are often nonspecific, they can sometimes yield clues to the diagnosis. (6) Commonly ordered lab tests include blood cultures, arterial blood gas (ABG) to evaluate level of hypoxia, complete blood count (CBC) with differential to evaluate anemia, chemistry, liver tests, blood urea nitrogen (BUN) ancreatinine for renal function, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis, and urine toxicology. (8) If the patient has a relevant past medical history or a pulmonary-renal syndrome disease, specific antibodies such as cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA), perinuclear anti- neutrophil cytoplasmic antibodies (P-ANCA), anti-nuclear antibody (ANA), anti-glomerular basement membrane (Anti-GBM), and rheumatoid factor should also be considered. (4) Serial pulmonary function testing can also help guide the clinician. Chronic DAH can cause restrictive changes.  Additionally, acute as well as chronic DAH can increase the diffusing capacity for carbon monoxide (DLCO). This is because blood in the alveoli can absorb carbon monoxide at a rapid rate. Both of these factors can be indirectly measured via pulmonary function tests, however both hemodynamic instability and patient cooperation can limit the value and reliability of these tests. (8)

Pearl: Transbronchial biopsy done concurrently with BAL is unlikely to help establish a diagnosis of DAH. (8)


Management of DAH has two goals. The first, which is more relevant for emergency medicine physicians, is to manage the airway, identify and stop any offending agent (s) if applicable, and administer immunosuppressive agents. The mainstay for moderate to severe DAH is methylprednisone (500-2000mg x 5 days IV followed by prednisone 1mg/kg PO) and cyclophosphamide (2mg/kg/day adjusted for renal function). The next goal is treating the specific underlying etiology. (1,8)

Pearl: Recent research shows that recombinant activated human factor VII is showing promise in treating DAH caused by ANCA-vasculitis and SLE, but further investigation must be done. (8)


  • DAH is a medical emergency characterized by bleeding of pulmonary microvasculature into the alveoli.
  • The clinical presentation is nonspecific – most commonly the patient will present with cough, dyspnea, fever, and hemoptysis. Though 33% will present without hemoptysis.
  • Cough, dyspnea, hemoptysis, and bronchoalveolar lavage (BAL) positive for RBCs is enough for a diagnosis
  • Consider the patient’s timeline of symptoms – acute hemorrhagic events are more likely to be caused by toxins than vasculitides.
  • Protecting the airway is the most important part of management. Then identify and stop the offending agent if possible and administer immunosuppressive
  • Mainstay for moderate to severe DAH is methylprednisone (500-2000mg x 5 days IV followed by prednisone 1mg/kg PO) and cyclophosphamide (2mg/kg/day adjusted for renal function)

References & Further Reading:

  1. Marx JA, Hockberger RS, Walls RM, et al., eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. Philadelphia, PA: Mosby/Elsevier; 2010
  2. Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med 2004;25:583–592, vii.
  3. Nguyen T, Martin MK, Indrikovs AJ. Plasmapheresis for diffuse alveolar hemorrhage in a patient with Wegener’s Granulomatosis: case report and review of the literature. J Clin Apher 2005;20:230–
  4. Ioachimescu, O. C., and J. K. Stoller 2008 Diffuse alveolar hemorrhage: diagnosing it and finding the cause. Cleve Clin J Med 75(4):258, 260, 264-5 passim.
  5. Kissner, Dana G., et al.1987 Crack Lung: Pulmonary Disease Caused by Cocaine Abuse. American Review of Respiratory Disease 136(5):1250-1252.
  6. Park, Moo Suk 2013. Diffuse alveolar hemorrhage. Tuberculosis and respiratory diseases 74(4):151-162.
  7. Sogomonian, R., et al. 2015 Refractile foreign material deposits and alveolar hemorrhage in crack cocaine smoker. Respir Med Case Rep 16:48-50.
  8. uptodate.com
  9. http://lifeinthefastlane.com/ccc/diffuse-alveolar-haemorrhage/
  10. https://www.thieme-connect.com/products/ejournals/html/10.1055/s-2002-35552

Pneumonia Mimics: Pearls and Pitfalls

Authors: Drew A. Long, BS (@drew2232, Vanderbilt University School of Medicine, US Army) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021, Senior Staff Physician, Henry Ford Hospital)

It’s a busy day in the ED. You have a full waiting room and multiple patients who have been roomed but not seen. You force your exhaustion to the back of your mind as you see your next patient: a 52-year-old male with cough and shortness of breath for three days. He states he has felt warm at home, but he denies chest pain, abdominal pain, vomiting, and diarrhea. He has experienced several episodes of nausea.  His past medical history includes hypertension and hyperlipidemia.

His vital signs include HR 103, RR 24, BP 128/72, T 99.8, and SpO2 95% on room air. He has some crackles in the lower lung bases, but has an otherwise normal physical exam. You order a chest x-ray, which demonstrates a right lower lobe infiltrate. As you write the diagnosis of “pneumonia” on the discharge form and write a prescription for antibiotics, you pause. Is there something else you could be missing? Are there other diagnoses you should consider?


Pneumonia is defined as an acute infection of the pulmonary alveoli.  Pneumonia can be life-threatening, most commonly in older patients with comorbidities or immunocompromised patients.  It is the 7th leading cause of death in the U.S. and the number one cause of death from infectious disease in the U.S.1   The annual incidence of community acquired pneumonia (CAP) ranges from 2 to 4 million, resulting in an estimated annual 500,000 hospitalizations.1  Pneumonia is broken into several categories: community-acquired (CAP), hospital-acquired, healthcare-associated (HCAP), and ventilator-associated (VAP) (Table 1).

Table 1.  Classification of Pneumonia (Adapted from Maloney G, Anderson E, Yealy DM.  Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  Chapter 65:  Pneumonia and Pulmonary Infiltrates.  McGraw Hill Professional 2016.  8th ed.)



Community-acquired pneumonia



Acute pulmonary infection in a patient who is not hospitalized or residing in a long-term care facility 14 or more days before presentation



Hospital-acquired pneumonia


New infection occurring 48 hours or more after hospital admission




Healthcare-associated pneumonia


Patients hospitalized ≥ 2 days within past 90 days

Nursing home/long-term care residents

Patients receiving home IV therapy

Dialysis patients

Patients receiving chronic wound care

Patients receiving chemotherapy

Immunocompromised patients



Pneumonia can be caused by bacteria, viruses, or fungi.  However, it is often challenging to differentiate between these in the ED, and many patients will not have an etiologic agent identified even after inpatient evaluation.   It is estimated that a microbial agent cannot be identified in nearly half of cases of CAP.1 The “typical” pathogens in patients hospitalized with pneumonia include S. pneumoniae and H. influenza, with S. pneumoniae being the most common.  The “typical” pathogens are thought to account for about half of cases.1 “Atypical” pathogens include Legionella, Mycoplasma, and Chlamydia.  The most common identified viral causes of pneumonia are influenza and parainfluenza viruses.  Fungal pneumonia is often associated with patients who are immunocompromised or possess other risk factors.1,2

History and Physical Examination

The classic presentation of pneumonia is a cough productive of purulent sputum, shortness of breath, and fever.  The most common signs of pneumonia include cough (79%-91%), fever (up to 75%), increased sputum (up to 65%), pleuritic chest pain (up to 50%), and dyspnea (approximately 70%).3 There are many patterns of presentation with a variety of these symptoms and physical findings, making the diagnosis at times difficult. Elderly or debilitated patients in particular can present with non-specific complaints, such as altered mental status without the classic symptoms.1,2 In addition, pneumonia may cause lightheadedness, malaise, weakness, headache, nausea/vomiting, joint pain, and rash.  The examination may reveal bronchial or decreased breath sounds, dullness on percussion, rales, rhonchi, or wheezing. This wide variation in symptoms and presentation provides potential for misdiagnosis, especially if other conditions are not considered.

The chest x-ray in patients with pneumonia can vary greatly.  Radiologic findings in pneumonia are used in conjunction with the physical exam to identify any area of consolidation.  The most common cause of pneumonia, S. pneumoniae, classically presents with a lobar infiltrate visualized on chest x-ray.  Other organisms, such as Staphylococcus aureus pneumonia can be seen on chest x-ray as extensive infiltration and effusion or empyema.  Klebsiella may present with diffuse, patchy infiltrates.  Other findings on chest x-ray found in various organisms include pleural effusions, basilar infiltrates, interstitial infiltrates, or abscesses.1,2,4 However, each agent can present multiple ways on chest x-ray, and many patients may not demonstrate the classic radiographic findings, especially elderly and immunocompromised patients with weakened immune systems.

PA chest radiograph showing left upper lobe pneumonia.  (Image from Marx JA.  Rosen’s Emergency Medicine:  Concepts and Clinical Practice.  Saunders 2014.  8th ed.)

 While it is tempting to diagnose pneumonia in a patient with a classic presentation (fever, cough, shortness of breath) and a supportive chest x-ray, what else should be considered?  As Table 2 shows, many conditions can be confused for pneumonia based on the history, physical exam, and radiographic findings.

Table 2.  Mimics of Pneumonia (Adapted from Marx JA.  Rosen’s Emergency Medicine:  Concepts and Clinical Practice and Maloney G, Anderson E, Yealy DM.  Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  Chapter 65:  Pneumonia and Pulmonary Infiltrates.)

Pulmonary Embolism
Septic Emboli
Congestive Heart Failure
Cancer and leukemic infiltrates
Acute Respiratory Distress Syndrome
Bronchiolitis obliterans organizing pneumonia
Granulomatous disease
Drug induced pulmonary disease
Pulmonary fibrosis
Eosinophilic pneumonia
Allergic/hypersensitivity pneumonitis
Radiation pneumonitis
Foreign body obstruction


Unfortunately, many of these diagnoses are not even considered in a patient with a classic presentation for pneumonia until the patient fails to improve with initial antibiotic management.  Of the diagnoses listed in Table 2, several of these carry high potential for morbidity and mortality.  These include pulmonary embolism, endocarditis, vasculitis, acute decompensated heart failure, tuberculosis, primary lung cancer, and acute respiratory distress syndrome.  The remainder of this discussion will focus on differentiating each of these from pneumonia.

*Bonus: What can potentially assist providers? Ultrasound (US)!

US has demonstrated tremendous utility differentiating pneumonia from other conditions. X-ray has a sensitivity of 46-77% in diagnosing pneumonia. US findings with pneumonia include air bronchograms, b-lines, consolidations, pleural line abnormalities, and pleural effusions. Dynamic air bronchograms (those that move) are considered pathognomonic for pneumonia.  Positive likelihood ratios (LR) for these findings range from 15.6 to 16.8, with negative LR’s of 0.03 to 0.07.5,6  Please see a prior emDocs.net post on the use of US in pneumonia: http://www.emdocs.net/ultrasound-for-pneumonia-in-the-ed/

Air bronchograms in pneumonia (From http://www.emdocs.net/ultrasound-for-pneumonia-in-the-ed/)

Pulmonary Embolism

Pulmonary embolism (PE) occurs when a thrombus, most commonly from the venous system, embolizes to the pulmonary vasculature.7,8 Like pneumonia, the clinical presentation of a PE can vary greatly, ranging from an asymptomatic patient to an ill-appearing, dyspneic patient.  PE can be easily confused with pneumonia, as the most common presenting symptom is dyspnea followed by pleuritic chest pain and cough.8,9 Fever can also be present in pulmonary embolism. The most common symptoms and their frequency are shown in Table 3.

Table 3.  Signs and Symptoms Of Pulmonary Embolism (adapted from Stein PD, Beemath A, Matta F, et al.  Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med. 2007;120(10):871.)

Sign/Symptom Frequency
Dyspnea 73%
Tachypnea 70%
Pleuritic Chest Pain 66%
Rales 51%
Cough 37%
Tachycardia 30%
S4 heart sound 24%
Accentuated P2 23%
Hemoptysis 13%
Circulatory collapse 8%


A PE most commonly has non-specific chest x-ray findings (atelectasis, pleural effusion, peripheral infarct/consolidation, elevated hemidiaphragm) or is normal.2  That being said, while a normal chest x-ray is helpful in distinguishing PE from pneumonia, a normal chest x-ray does not definitively exclude pneumonia or pulmonary embolism.  Hampton’s Hump (peripheral wedge-shaped opacity with base against pleural surface) and Westermark’s Sign (focus of oligemia and vessel collapse distal to the PE) are classic findings in the PE radiograph, but they lack sensitivity.

The important aspect of not missing PE is first considering it. As the presentation of PE is nonspecific, clinical gestalt and risk stratification are useful. Evaluate the patient for signs/symptoms of PE including shortness of breath with pleuritic chest pain, tachypnea, and leg swelling in the setting of risk factors such as recent travel history, prior history of thrombosis, family history of thrombosis, or history of cancer.  If signs and/or symptoms are present and concerning, do not hesitate to begin the workup for PE.

In PE, US may reveal RV strain with dilated RV and free wall hypokinesis and normal RV apical contractility (McConnell Sign). On short axis view, the LV will appear “D” shaped, with RV bowing into the LV due to elevated right-sided pressures.10-12

Enlarged RV when compared to LV in setting of acute PE (from www.em.emory.edu)


Endocarditis is most commonly caused by a bacterial agent, with a one-year mortality of 40%.13 The most common symptoms are intermittent fever (85%) and malaise (80%).1  Additionally, endocarditis can present with dyspnea, chest pain, cough, headache, weakness, and myalgias.  Infective endocarditis (IE) can easily be confused with pneumonia in a patient presenting with fever and dyspnea or chest pain.  Risk factors for IE are shown below in Table 4.  Diagnosis includes the Duke Criteria. A patient with flu-like symptoms (cough, myalgias, etc.) with the risk factors shown in Table 4, warrants further evaluation for IE. 13-17

Table 4.  Risk factors for IE

Age ≥ 60 (over half of cases occur in this population)
History of IV drug use
Poor dentition or dental infection
Structural heart disease (e.g. valvular or congenital)
Presence of prosthetic valve
Presence of intravascular device
Chronic hemodialysis


One of the most important aspects to not miss is the patient with multiple infiltrates on chest x-ray, as a dreaded complication of IE is septic emboli.  This has been described in 13 to 44% of patients with IE.18,19 Septic emboli can lead to damage in the systemic or pulmonary artery circulation, depending on left vs. right-sided disease.  Specifically, embolization can lead to stroke, paralysis, blindness, ischemia of the extremities, splenic or renal infarction, pulmonary emboli, or an acute myocardial infarction.18 In particular, septic emboli from the right heart to the pulmonary arteries can lead to a toxic-appearing patient with fever and shortness of breath.  Again, the chest x-ray may demonstrate multiple infarcts or consolidations. This patient may originally be worked up for pneumonia.  In the patient with IE risk factors described above and multiple consolidations/infarcts on chest x-ray, strongly consider IE and obtain multiple blood cultures and echocardiogram.  US may reveal valvular vegetation(s) and/or regurgitation.

Multiple emboli with consolidations from R sided IE (From https://www.roshreview.com/em.html)
Valvular Regurgitation with Vegetation in Endocarditis (From Journal of Medicine Cases, http://www.journalmc.org/index.php/JMC/article/view/286/212)

Vasculitis (Systemic Lupus Erythematosus)

A vasculitis that often manifests with pulmonary involvement is systemic lupus erythematosus (SLE).  SLE is an autoimmune disorder that leads to inflammation of multiple organ systems.  Pulmonary involvement is common and has been observed in up to 93% of patients with SLE.20,21 Lung involvement in SLE often manifests as pleurisy, coughing, and/or dyspnea.21-23 The most common respiratory condition among patients with SLE is pleuritis, thought to be due to autoantibodies damaging the pleura itself.1 Pneumonitis may also occur in the setting of SLE. Patients with acute lupus pneumonitis present with a rapid onset of fever, cough, and dyspnea, with elevation of serum antinuclear antibodies and anti-DNA antibodies.22,23

Patients with SLE (either diagnosed or undiagnosed) and lung involvement should be worked up for infection.  Since patients with SLE are often immunosuppressed due to immunomodulatory therapy and the disease itself, they are at a much higher risk of infection with both typical and opportunistic agents.  The patient with extrapulmonary features of SLE (e.g. malar rash, oral ulcers, polyserositis, renal insufficiency, cytopenia, thrombophilia, lymphadenopathy, splenomegaly, or arthritis) and signs of lung involvement warrants treatment for infection and worsening vasculitis. Consultation with rheumatology and the ICU is recommended due to the potential for rapid decompensation.

Diffuse alveolar hemorrhage (DAH) is one of the most life-threatening conditions in SLE. Diffuse alveolar damage is a more common presentation in patients who already have a documented history of lupus and rarely presents as the initial manifestation of lupus.  These patients present with severe shortness of breath, hemoptysis, and diffuse patchy infiltrates on chest x-ray. Patients often require intubation, ICU admission, and high dose steroids.24-26

Heart Failure Exacerbation

A patient with heart failure exacerbation can present similarly to a patient with pneumonia, particularly if a patient has undiagnosed heart failure.  Patients with acute decompensated heart failure most commonly present with cough, shortness of breath, fatigue, and/or peripheral edema.  The history and physical exam may be enough to differentiate a heart failure exacerbation from pneumonia.  A history of orthopnea and/or paroxysmal nocturnal dyspnea leading up to the patient’s presentation is sensitive and specific for heart failure.  Furthermore, many of these patients will have a cardiac history, history of cardiac procedures, and comorbid conditions for CHF (such as diabetes, hypertension, hyperlipidemia, or a history of smoking).  Physical exam may reveal an S3 or S4 heart sound, elevated jugular venous pressures, lower extremity edema, and crackles indicating interstitial pulmonary edema on auscultation of the lungs.  These patients often have nonspecific EKGs showing left-ventricular hypertrophy, bundle branch block, or signs of a previous MI such as prominent Q waves or T wave inversions.  BNP will more likely be elevated in CHF exacerbations, though sepsis from pneumonia can also increase BNP.1,27

The chest x-ray findings in CHF may include prominent interstitial markings, cardiomegaly, and pleural effusions.2

CXR in a patient with CHF depicting cardiomegaly, alveolar, and interstitial edema (From https://www.med-ed.virginia.edu/courses/rad/cxr/pathology2Bchest.html)

US in the setting of CHF will reveal b-lines in 3 or more lung fields bilaterally, which has a +LR of 20. The IVC will often reveal significant distension, with 2-2.5cm in size and < 50% collapse. Echocardiogram may reveal depressed contractility if systolic dysfunction is present.28

Multiple b-lines in the setting of acute CHF (From canadiem.org, http://canadiem.org/2015/01/19/us-world-ultrasound-differentiating-copd-chf/)


Tuberculosis (TB) is currently the world’s second leading infectious cause of death.1 The lungs are the major site for infection with Mycobacterium tuberculosis.  TB can occur in multiple forms, including primary TB, reactivation TB, laryngeal TB, endobronchial TB, lower lung field TB infection, and tuberculoma.29 As TB affects the lungs and can present with fever, cough, or dyspnea, it is often misdiagnosed as viral or bacteria pneumonia.  There are a wide array of nonspecific signs and symptoms associated with the multiple forms of TB, shown in Table 5.30

Table 5.  Symptoms and Signs of Tuberculosis (Adapted from Barnes PF, et al:  Chest roentgenogram in pulmonary TB: new data on an old test. Chest. 94:316, 1988.)

Symptom or Sign Frequency
Cough 78%
Weight loss 74%
Fatigue 68%
Tactile fever 60%
Night sweats 55%
Chills 51%
Anorexia 46%
Chest pain 40%
Dyspnea 37%
Hemoptysis 28%


In differentiating TB from pneumonia, it is important to assess the patient for risk factors for TB.  The most commonly reported behavioral risk factor among patients with TB in the U.S. is substance abuse (including drugs, tobacco, and alcohol).31 Other risk factors include malnutrition, systemic disease (silicosis, malignancy, diabetes, renal disease, celiac disease, or liver disease), or patients who are immunocompromised or homeless.32  Additionally, TB should be considered when a patient has a history of recent travel to an area where TB is endemic (Africa, the Middle East, Southeast and East Asia, and Central and South America).33

 As TB has many forms, the chest x-ray in TB can vary and may not be all that helpful in differentiating TB from pneumonia.  In summary, TB should be suspected in a patient with vague symptoms who possesses risk factors for TB, particularly in patients who are homeless, immunosuppressed, have a history of drug use, or have recently traveled to a TB endemic area.

Primary Lung cancer

In 2012, lung cancer worldwide was the most common cancer in men and the third most common cancer in women.34 In the U.S., lung cancer occurs in an estimated 225,000 patients every year and is responsible for over 160,000 deaths.35 There are many risk factors for cancer, the most notorious of which is smoking.

A patient with a primary lung cancer can easily be confused with pneumonia due to the similarity of symptoms (Table 6).  What is key in primary lung cancer is these symptoms have a more insidious onset than the relatively more acute onset of symptoms in pneumonia. Furthermore, these symptoms will progress over time and may include symptoms less commonly seen in pneumonia (weight loss, bone pain, or voice hoarseness).

Table 6.  Symptoms of lung cancer at presentation.  (Modified from: Hyde, L, Hyde, CI. Chest 1974; 65:299-306 and Chute CG, et al. Cancer 1985; 56:2107-2111).

Symptom Percent of Patients Affected
Cough 45-74%
Weight Loss 46-68%
Dyspnea 37-58%
Chest pain 27-49%
Hemoptysis 27-29%
Bone pain 20-21%
Hoarseness 8-18%


The chest x-ray in patients with lung cancer varies depending on the type and stage of cancer.  The chest x-ray in patients with a primary lung cancer may display a solitary nodule, an interstitial infiltrate, or may be normal.2

Non-small cell lung cancer.  (Image from http://emedicine.medscape.com/article/358433-overview)

 If considering a primary lung malignancy in a patient whose presentation is consistent with pneumonia, more definitive imaging including CT of the chest may be warranted. Discussion with the oncology service is advised.

Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) is acute, diffuse, inflammatory lung injury that carries high rates of morbidity, ranging from 26 to 58%.35,36 ARDS stems from diffuse alveolar damage and lung capillary endothelial injury, leading to increased capillary permeability and pulmonary edema.1 This disease manifests with respiratory distress, with patients often displaying tachycardia, tachypnea, hypoxemia, and dyspnea.37 Arterial blood gas analysis shows hypoxemia in addition to acute respiratory alkalosis and increased alveolar-arterial oxygen gradient (though ABG is usually not required in the ED).  A chest radiograph will typically reveal bilateral alveolar infiltrates, and classically, no cardiomegaly is seen.2

Chest radiograph depicting bilateral lung opacities in a patient with ARDS.  (Image from http://emedicine.medscape.com/article/362571-overview#a2)

When considering ARDS, several factors come into play.  The diagnosis of ARDS is complicated, as the most common cause or ARDS is sepsis. Thus, ARDS may result from a prior pneumonia leading to sepsis. The patient with ARDS will appear sick and will likely require high levels of FiO2 or positive pressure ventilation if not intubated, while the severity of pneumonia varies greatly based on the patient and infectious microbe.  Risk factors such as sepsis, aspiration, and multiple transfusions are commonly seen with ARDS.38 Other risk factors for ARDS include alcohol abuse, trauma, and smoke inhalation.  On physical exam, patients with ARDS often have diffuse crackles on auscultation of the lungs.  The chest x-ray shows more diffuse involvement than would be expected in a patient with pneumonia.2 US will reveal b-lines in multiple lung fields.  If concerned for ARDS, be ready to intubate the patient for clinical course/oxygenation and admit to the ICU.

Case resolution

As you return to this 52-year-old gentleman’s room with his prescription for antibiotics, you notice that he remains tachycardic, tachypneic, and hypoxic (HR 105, RR 24, SpO2 93%).  You perform a more complete review of systems and find out this gentleman has been experiencing pain in his right calf over the past week after returning from an overseas business trip.  On exam, you notice that his right lower extremity is slightly edematous compared to the left.  In addition to pneumonia, you decide to begin to work up this gentleman for a possible deep venous thrombosis and pulmonary embolism.  A chest CT reveals a large right-sided segmental PE.


Many potentially deadly conditions can be confused for pneumonia.  Unfortunately, many of these conditions are not considered until the patient fails to improve after treatment with antibiotics.  The following should be considered in a patient presenting with signs of pneumonia:

  • Pulmonary embolism: suspect when a patient has signs/symptoms of PE including shortness of breath with pleuritic chest pain, tachypnea, and leg swelling in the setting of risk factors for DVT/PE.
  • Endocarditis/septic emboli: consider in febrile patients with risk factors including history of IV drug use, poor dentition, structural heart disease, or the presence of a prosthetic valve. Septic emboli leading to pulmonary infarction can present with multiple infiltrates on chest x-ray.
  • Systemic Lupus Erythematosus: pulmonary involvement is very common in lupus. Patients with SLE and lung involvement must always be evaluated for infection, and diffuse alveolar hemorrhage is a life-threatening complication.
  • Heart Failure exacerbation: suspect in a patient with cardiac history and signs/symptoms of heart failure (orthopnea, PND, peripheral edema, elevated jugular venous distension, etc.).
  • Tuberculosis: suspect in patients with risk factors for TB including substance abuse, malnutrition, systemic diseases, immunocompromise, or recent foreign travel.
  • Lung cancer: suspect in patients with insidious onset of symptoms and in patients complaining of constitutional symptoms such as weight loss or fatigue.
  • Acute Respiratory Distress Syndrome: suspect in toxic-appearing patients with white-out on chest x-ray who require high levels of FiO2 or positive pressure ventilation.


References/Further Reading

  1. Marx JA. Rosen’s Emergency Medicine:  Concepts and Clinical Practice.  Saunders 2014.  8th
  2. Maloney G, Anderson E, Yealy DM. Tintinalli’s Emergency Medicine:  A Comprehensive Study Guide.  Chapter 65:  Pneumonia and Pulmonary Infiltrates.  McGraw Hill Professional 2016.   8th
  3. Fine MJ, Stone RA, Singer DE et al. Processes and outcomes of care for patients with community-acquired pneumonia:  results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study.  Arch Intern Med 159:  970, 1999.
  4. Bartlett JG. Diagnostic approach to community-acquired pneumonia in adults.  UpToDate.  Jan 2016.
  5. Hu QJ, Shen YC, Jia LQ, et al. Diagnostic performance of lung ultrasound in the diagnosis of pneumonia: a bivariate meta-analysis. Int J Clin Exp Med. 2014;7(1):115-21. [pubmed]
  6. Chavez MA, Shams N, Ellington LE, et al. Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. Respir Res. 2014;15:50. [pubmed]
  7. Thompson BT. Overview of acute pulmonary embolism in adults.  UpToDate.  Jan 2016.
  8. Thompson BT. Clinical presentation, evaluation, and diagnosis of the adult with suspected acute pulmonary embolism.  UpToDate.  Jan 2016.
  9. Stein PD, Beemath A, Matta F, et al. Clinical characteristics of patients with acute pulmonary embolism:  data from PIOPED II.  Am J Med.  2007;120(10):871.
  10. Perera, T. Mailhot, D. Riley, and D. Mandavia, “The RUSH exam: rapid ultrasound in Shock in the evaluation of the critically ill,” Emergency Medicine Clinics of North America, vol. 28, no. 1, pp. 29–56, 2010.
  11. P. Borloz, W. J. Frohna, C. A. Phillips, and M. S. Antonis, “Emergency department focused bedside echocardiography in massive pulmonary embolism,” Journal of Emergency Medicine, vol. 41, no. 6, pp. 658–660, 2011.
  12. Madan and C. Schwartz, “Echocardiographic visualization of acute pulmonary embolus and thrombolysis in the ED,” American Journal of Emergency Medicine, vol. 22, no. 4, pp. 294–300, 2004.
  13. Murdoch DR, Corey GR, Hoen B. Clinical Presentation, Etiology and Outcome of Infective Endocarditis in the 21st Century:  The International Collaboration on Endocarditis-Prospective Cohort Study.  Arch Intern Med.  2009 Mar 9;169(5):463-473.
  14. Sexton DJ. Epidemiology, risk factors, and microbiology of infective endocarditis.  UpToDate.  Jan 2016.
  15. Hill EE, Herijgers P, Claus P. Infective endocarditis:  changing epidemiology and predictors of 6-month mortality:  a prospective cohort study.  Eur Heart J.  2007;28(2):196.
  16. Cantrell M, Yoshikawa TT. Infective endocarditis in the aging patient.  Gerontology.  1984;30(5):316.
  17. Castillo FJ, Anguita M, Castillo JC, et al. Changes in the Clinical Profile, Epidemiology and Prognosis of Left-sided Native-valve Infective Endocarditis Without Predisposing Heart Conditions.  Rev Esp Cardiol (Engl Ed).  2015 May;68(5):445-8.  Epub 2015 Mar 16.
  18. Spelman D, Sexton DJ. Complications and outcome of infective endocarditis.  UpToDate.  Jan 2016.
  19. Steckelberg JM, Murphy JG, Ballard D, et al. Emboli in infective endocarditis:  the prognostic value of echocardiography.  Ann Intern Med.  1991;114(8):635.
  20. Dellaripa PF, Danoff Sonye. Pulmonary manifestations of systemic lupus erythematosus in adults.  UpToDate.  Jan 2016.
  21. King Jr. TE, Kim EJ, Kinder BW. Connective tissue diseases:  In:  Interstitial Lung Disease, 5th, Schwartz MI, King TE Jr. (Eds), People’s Medical Publishing House-USA, Shelton, CT 2011.
  22. Matthay RA, Schwarz MI, Petty TL, et al. Pulmonary manifestations of systemic lupus erythematosus:  review of twelve cases of acute lupus pneumonitis.  Medicine (Baltimore).  1975;54(5):397.
  23. Wiedemann HP, Matthay RA. Pulmonary manifestations of systemic lupus erythematosus.  J Thorac Imaging.  1992;7(2):1.
  24. Zamora MR, Warner ML, Tuder R, Schwarz MI. Diffuse alveolar hemorrhage and systemic lupus erythematosus.  Clinical presentation, histology, survival, and outcome.  Medicine (Baltimore).  1997;76(3):192. 
  25. Andrade C, Mendonca T, Farinha F, et al. Alveolar hemorrhage in systemic lupus erythematosus:  a cohort review.  Lupus.  2016 Jan;25(1):75-85.  Epub 2015 Sep 18.
  26. Collard HR, Schwarz MI. Diffuse alveolar hemorrhage. Clin Chest Med 2004;25:583–592, vii.
  27. Borlaug BA. Clinical manifestations and diagnosis of heart failure with preserved ejection fraction.  UpToDate.  Jan 2016.
  28. Ang S-H, Andrus P. Lung Ultrasound in the Management of Acute Decompensated Heart Failure. Current Cardiology Reviews. 2012;8(2):123-136.
  29. Pozniak A. Clinical manifestations and complications of pulmonary tuberculosis.  UpToDate.  Jan 2016.
  30. Barnes PF, et al: Chest roentgenogram in pulmonary TB:  new data on an old test.  94:316, 1988.
  31. Oeltmann JE, Kammerer JS, Pevzner ES, Moonan PK. Tuberculosis and substance abuse in the United States, 1997-2006.  Arch Intern Med.  2009;169(2):189.
  32. Horsburgh CR. Epidemiology of tuberculosis.  UpToDate.  Jan 2016.
  33. World Health Organization. Global Tuberculosis Report 2014. http://www.who.int.proxy.library.vanderbilt.edu/tb/publications/global_report/en/.
  34. World Cancer Research Fund International. Worldwide Data.  http://www.wcrf.org/int/cancer-facts-figures/worldwide-data.
  35. MacCallum NS, Evans TW. Epidemiology of acute lung injury.  Curr Opin Crit Care.  2005;11(1):43.
  36. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury.  N Engl J Med.  2005;353(16):1685.
  37. Hansen-Flaschen J, Siegel MD. Acute respiratory distress syndrome:  Clinical features and diagnosis in adults.  UpToDate.  Jan 2016.
  38. Siegel MD. Acute respiratory distress syndrome:  Epidemiology, pathophysiology, pathology, and etiology in adults.  UpToDate.  Jan 2016.

R.E.B.E.L. EM – Is Too Much Supplemental O2 Harmful in COPD Exacerbations?

Originally published at R.E.B.E.L. EM on December 3, 2015. Reposted with permission.

Follow Dr. Salim R. Rezaie (@srrezaie) on twitter


Background: It’s common practice to give carefully titrated supplemental oxygen therapy for patients in COPD exacerbation. We give enough O2 to prevent hypoxemia, but not so much that it causes hypoventilation or dangerous hypercarbia. If you’re like me then you’ve probably heard a number of conflicting theories as to WHY overzealous supplemental oxygen leads to bad outcomes in these patients.

Does hyperoxia suppress a COPD patient’s respiratory drive? Does it cause V/Q mismatching? Does it change the chemistry of the patient’s blood through the Haldane effect? It’s enough to make you want to give up and page respiratory therapy. Well lucky for you we sifted through the primary literature to bring you the myths and facts, and the short answer is…it’s complicated.

Theory 1: Oxygen Induced Hypoventilation

One commonly cited theory goes like this:

There are two central drivers of respiratory drive, hypercarbia and hypoxemia. Because COPD patients spend their lives chronically hypercarbic they no longer respond to that stimulus, and their only trigger for respiratory drive is the level of oxygen (or lack their of) in their blood. Supplemental O2 removes a COPD patient’s hypoxic respiratory drive causing hypoventilation with resultant hypercarbia, apnea, and ultimate respiratory failure. The first study to really investigate this theory was done in 1980 [1].

Aubier M et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis.1980;122(5):747–754.

Population: 22 ICU patients with known COPD in acute respiratory failure

Methods: Minute ventilation and PaCO2 were measured in all patients first while breathing room air and then while breathing supplemental oxygen.

Effect of minute ventilation during oxygen-induced hypercapnia. (Abdo WF 2012)

Effect of minute ventilation during oxygen-induced hypercapnia. (Abdo WF 2012)

Results: All patients had an initial drop in minute ventilation (Ve) once placed on supplemental O2 but Ve then recovered to near baseline levels. At the same time PaCO2 continued to increase (figure 1). There was NO correlation between minute ventilation and the increase in PaCO2.

Conclusions: The study subjects had a transient drop off in minute ventilation on supplemental oxygen therapy, but it did not correlate with steadily increasing PaCO2 levels. A follow up study showed that respiratory drive and minute ventilation both stayed within normal limits on supplemental O2 [2]. The authors suggested that hypoventilation due to loss of hypoxic respiratory drive WAS NOT the cause of hypercarbia after O2 administration, and that other factors, like the Haldane effect and V/Q mismatching were likely to blame.

Theory 2: The Haldane Effect

This brings us to a second theory, the Haldane effect.

The amine groups of proteins in our blood, like hemoglobin (Hb), combine with CO2 to form carbamino compounds. The ability of deoxygenated Hb to bind CO2 is much higher than that of oxygenated Hb (this makes some physiologic sense, because Pa CO2 should be higher in venous blood). Supplemental O2 shifts the equilibrium between deoxygenated and oxygenated Hb more towards the oxygenated form. This reduces the amount of CO2 that can be bound, and that CO2 winds up dissolved in the blood, resulting in an increased Pa CO2.

The chemistry behind this theory is sound, but it’s proved understandably tricky to study in practice. Again we rely on the 1980 Aubier et al study [1]. They calculated how much of the observed change Pa CO2 could be due to the Haldane effect based on the observed change in Hb O2 saturation in their patients. They concluded that the effect, while presumably real, could only have accounted for about 25% of the increase. In other words there just wasn’t enough bound CO2 to dislodge.

It follows that there must be ANOTHER physiologic change at work, which leads us to…

Theory 3: Ventilation Perfusion (V/Q) Mismatch

The pulmonary vasculature can dilate and constrict to alter blood flow and match ventilation to perfusion (figure 2), and the primary driver of vascular dilation and increased perfusion is alveolar O2.

COPD patients have diseased lungs, and over time their bodies have carefully allocated perfusion to parts of their lungs that work, and away form the parts that don’t. Administering supplemental O2 screws up this careful balance. Diseased sections of lung see increased PaO2 and steal perfusion away from better functioning areas. This results in shunting, dead space ventilation, and eventually hypercarbia.

Hypoxic pulmonary vasoconstriction (Abdo WF 2012)

Hypoxic pulmonary vasoconstriction (Abdo WF 2012)

Aubier et al inferred that V/Q mismatch was the primary driver of hypercabia after O2 supplementation, but a follow up study 20 years later looked at it more directly, and their findings muddied the waters [3].

Robinson et al. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161(5):1524–1529.

Population: 22 hospitalized patients with a diagnosis of acute COPD exacerbation

Methods: Inert gas was infused into each patient using a peripheral venous catheter. Expired air makeup and arterial blood gas readings were recorded in each patient while breathing room air, and then 100% supplemental O2. The patients were classified as CO2 ‘retainers’ if their Pa CO2 rose by more than 3mmhg while on supplemental O2 and as ‘non-retainers’ if it did not. The authors then compared minute ventilation, V/Q matching (calculated based on the expired inert gas), and dead space ventilation between the two groups.

Results: Ventilation perfusion heterogeneity (i.e. V/Q mismatch) increased significantly in both the retainer and non-retainer groups. Minute ventilation decreased significantly in the retainers but not the non-retainers. Finally, dead space ventilation increased significantly in the retainer group, but was unchanged in the non-retainer group.

Conclusions: Since V/Q mismatch increased in both retainers and non-retainers the authors concluded that V/Q mismatch could not be the cause of observed CO2 retention (hypercarbia). Further, because minute ventilation decreased in the retainer group, but remained stable in the non-retainers they proposed that OXYGEN INDUCED HYPOVENTILATION was to blame.


That’s right. Robinson et al came to the exact opposite conclusion that Aubier et al did 20 years earlier in their landmark study. They concluded that hypoventilation (theory #1, which I just called a myth) was the cause of oxygen induced hypercapnia in COPD patients. But just in case you’re not confused enough; it’s not quite that simple.

Controversy: Other authors have drawn different conclusions from the Robinson et al study. For example, Abdo and Heunks [4] suggest that hypercarbia in the retainer group was likely due to the increase in dead space ventilation (which was unchanged in the non-retainers). The retainer group did show a decrease in minute ventilation, but so did the patients in Aubier’s 1980 study (that decreases just wasn’t large enough to account for all the observed hypercarbia). It’s plausible that although V/Q mismatch increased in both groups, it only caused hypercarbia in the retainer group because it increased dead space ventilation in their lungs.

It’s an interesting theory and it fits nicely with the prior literature, but it’s important to stress that it directly contradicts the authors who actually conducted the study.

The Bottom Line:

I hope this has been an enjoyable tour through pulmonary physiology. Let’s see if we can make any sense of the myths and facts of oxygen induced hypercarbia in COPD patients.

Theory 1: Oxygen Induced Hypoventilation

 Myth or Fact?


Both large studies that looked at this theory found that supplemental O2 does lead to hypoventilation. Aubier et al. concluded that it was transient and DID NOT account for the observed hypercarbia. Robinson et al. concluded that IT DID.

Theory 2: The Haldane Effect

Myth or Fact?

 Probably Fact… But

 The chemistry is sound, and the effect likely causes some hypercarbia, but we have minimal direct evidence for it. It also cannot account for all of the hypercarbia that has been observed in the above studies.

Theory 3: V/Q Mismatch

 Myth or Fact?


Aubrier et al. concluded by process of elimination that V/Q mismatch should be responsible for most of the observed hypercarbia. Robinson et el found that V/Q mismatch increased in both retainers and non-retainers and therefore could not be the cause; however, other authors point out that dead space ventilation increased in the retainer group, and suggest that this specific type of V/Q mismatch could be the cause of hypercarbia.

Guest Contributor:

Allan Guiney 4-5-14

Allan Guiney, MD
Resident Physician
NYU/Bellevue Department of Emergency Medicine
New York, NY


  1. Aubier M, Murciano D, Milic-Emili J, et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis.1980;122(5):747–754. PMID: 66778278
  2. Aubier M, Murciano D, Fournier M, Milic-Emili J, Pariente R, Derenne JP: 
Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1980, 122:191-199. PMID: 67746339
  3. Robinson TD, Freiberg DB, Regnis JA, Young IH. The role of hypoventilation and ventilation-perfusion redistribution in oxygen-induced hypercapnia during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161(5):1524–1529. PMID: 10806149
  4. Abdo WF, Heunks LMA: Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care 2012, 16:323. PMID: 23106947

Post Peer Reviewed By: Salim Rezaie (Twitter: @srrezaie)